NOAEL Studies
Active Ingredient
Soy Isoflavones NOAEL Studies
INCI: SOY ISOFLAVONES
CAS: 446-72-0
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
NTP_ICE_adme_parameters 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_adme_parameters | Clint | 18.69 | uL/min/10^6 cells | Human | - | - | Measured; httk, Human Hepatic Intrinsic Clearance | sheet=Data; excel_row=1990; Record_ID=adme_parameters_345; Data_Type=Measured; DTXSID=DTXSID5022308; Assay=httk, Human Hepatic Intrinsic Clearance; Endpoint=Clint; Response=18.69; Response_Unit=ul/min/10^6 cells; Species=Human; Reference=httk2.3.1, Wetmore 2015; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_adme_parameters | Clint | 68 | uL/min/10^6 cells | Rat | - | - | Measured; httk, Rat Hepatic Intrinsic Clearance | sheet=Data; excel_row=1989; Record_ID=adme_parameters_345; Data_Type=Measured; DTXSID=DTXSID5022308; Assay=httk, Rat Hepatic Intrinsic Clearance; Endpoint=Clint; Response=68.0; Response_Unit=ul/min/10^6 cells; Species=Rat; Reference=httk2.3.1, Honda 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_adme_parameters | Fu | 0.0085 | fraction | Rat | - | - | Measured; httk, Rat Plasma Fraction Unbound | sheet=Data; excel_row=1987; Record_ID=adme_parameters_345; Data_Type=Measured; DTXSID=DTXSID5022308; Assay=httk, Rat Plasma Fraction Unbound; Endpoint=Fu; Response=0.0085; Response_Unit=Unitless Fraction; Species=Rat; Reference=httk2.3.1, Honda 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_adme_parameters | Fu | 0.02426 | fraction | Human | - | - | Measured; httk, Human Plasma Fraction Unbound | sheet=Data; excel_row=1988; Record_ID=adme_parameters_345; Data_Type=Measured; DTXSID=DTXSID5022308; Assay=httk, Human Plasma Fraction Unbound; Endpoint=Fu; Response=0.02426; Response_Unit=Unitless Fraction; Species=Human; Reference=httk2.3.1, Wetmore 2015; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
NTP_ICE_cancer 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_cancer | POLY-3 lowest dose | 500 | ppm | Rat | Dosed feed | - | In Vivo; Two year cancer bioassay | sheet=Data; excel_row=5853; Record_ID=cancer_1621; Data_Type=In Vivo; Formulation_Name=Genistein; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Two year cancer bioassay; Endpoint=POLY-3 lowest dose; Response=500; Response_Unit=ppm; Species=Rat; Strain=Sprague Dawley; Sex=Female; Route=Dosed feed; Level_of_Evidence=Some evidence; Tissue=Pituitary gland; Location=Pars distalis or unspecified site; Lesion=Carcinoma or adenoma; Reference=TR-545; URL=https://ntp.niehs.nih.gov/publications/reports/tr/500s/tr545/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_cancer | Top dose | 500 | ppm | Rat | Dosed feed | - | In Vivo; NTP Carcinogenicity | sheet=Data; excel_row=5852; Record_ID=cancer_1619; Data_Type=In Vivo; Formulation_Name=Genistein; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=NTP Carcinogenicity; Endpoint=Top dose; Response=500; Response_Unit=ppm; Species=Rat; Strain=Sprague Dawley; Sex=Male; Route=Dosed feed; Reference=TR-545; URL=https://ntp.niehs.nih.gov/publications/reports/tr/500s/tr545/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
NTP_ICE_endocrine 56 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_endocrine | AC50 | 0.33676788105873 | uM | - | - | - | ERPathway2016; ER Pathway Model, Antagonist | sheet=Integrated_approaches; excel_row=9958; RecordID=ERPathway2016_156; DatasetName=ERPathway2016; DTXSID=DTXSID5022308; Assay=ER Pathway Model, Antagonist; Endpoint=AC50; Response=0.33676788105873; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 3.7 | nM | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=191; Record_ID=endocrine_invitro_185; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=AC50/EC50/IC50; Reported_Response=1000; Reported_Response_Unit=ng/L; Conversion_Factor=Molecular Weight; Conversion_Factor_Value=270.24; Conversion_Factor_Source=EPA Dashboard; Converted_Response=3.7004144464179989; Converted_Response_Unit=nM; Response=3.7; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 162.2 | nM | - | - | - | In Vitro; AR Transactivation-Agonist | sheet=Data_invitro; excel_row=7848; Record_ID=endocrine_invitro_3469; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Transactivation-Agonist; Endpoint=AC50/EC50/IC50; Reported_Response=162.1810097; Reported_Response_Unit=nM; Response=162.2; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Bartonkova et al. 2015; 25811655; 10.1371/journal.pone.0121316; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 239.9 | nM | - | - | - | In Vitro; AR Transactivation-Agonist | sheet=Data_invitro; excel_row=7847; Record_ID=endocrine_invitro_3468; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Transactivation-Agonist; Endpoint=AC50/EC50/IC50; Reported_Response=239.88329189999999; Reported_Response_Unit=nM; Response=239.9; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Bartonkova et al. 2015; 25811655; 10.1371/journal.pone.0121316; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 84500 | nM | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=128; Record_ID=endocrine_invitro_122; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=AC50/EC50/IC50; Reported_Response=84500; Reported_Response_Unit=nM; Response=84500; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Fang et al. 2003; 14565775; 10.1021/tx030011g; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 100000 | nM | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=131; Record_ID=endocrine_invitro_125; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=AC50/EC50/IC50; Reported_Response=100000; Reported_Response_Unit=nM; Response=100000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Pfitscher et al. 2008; 18809497; 10.1016/j.jsbmb.2008.08.007; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 140000 | nM | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=232; Record_ID=endocrine_invitro_226; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=AC50/EC50/IC50; Reported_Response=140000; Reported_Response_Unit=nM; Response=140000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Freyberger and Ahr 2004; 14751668; 10.1016/j.tox.2003.09.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 155000 | nM | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=233; Record_ID=endocrine_invitro_227; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=AC50/EC50/IC50; Reported_Response=155000; Reported_Response_Unit=nM; Response=155000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Freyberger and Ahr 2004; 14751668; 10.1016/j.tox.2003.09.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 270000 | nM | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=478; Record_ID=endocrine_invitro_472; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=AC50/EC50/IC50; Reported_Response=270000; Reported_Response_Unit=nM; Response=270000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Ichige et al. 2013; 23402539; 10.1021/jf305233t; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | AC50/EC50/IC50 | 1300000 | nM | - | - | - | In Vitro; AR Transactivation-Antagonist | sheet=Data_invitro; excel_row=13274; Record_ID=endocrine_invitro_4113; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Transactivation-Antagonist; Endpoint=AC50/EC50/IC50; Reported_Response=1300000; Reported_Response_Unit=nM; Response=1300000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | ACC | 0.0615586769783145 | uM | - | - | - | ERPathway2016; ER Pathway Model, Antagonist | sheet=Integrated_approaches; excel_row=9959; RecordID=ERPathway2016_156; DatasetName=ERPathway2016; DTXSID=DTXSID5022308; Assay=ER Pathway Model, Antagonist; Endpoint=ACC; Response=0.0615586769783145; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | EC50 | 271 | nM | - | - | - | In Vitro; ER Transactivation-Agonist (VM7Luc Assay) | sheet=Data_invitro; excel_row=16617; Record_ID=endocrine_invitro_4456; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=ER Transactivation-Agonist (VM7Luc Assay); Endpoint=EC50; Reported_Response=2.7099999999999998E-7; Reported_Response_Unit=M; Conversion_Factor=1000000000; Conversion_Factor_Value=1000000000; Converted_Response=270.99999999999903; Converted_Response_Unit=nM; Response=271; Response_Unit=nM; Reference=|OECD TG 455; https://www.oecd.org/env/test-no-455-performance-based-test-guideline-for-stably-transfected-transactivation-in-vitro-assays-to-detect-estrogen-receptor-9789264265295-en.htm; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LEL | 1 | nM | - | - | - | In Vitro; AR Transactivation-Antagonist | sheet=Data_invitro; excel_row=14871; Record_ID=endocrine_invitro_4243; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Transactivation-Antagonist; Endpoint=LEL; Reported_Response=1; Reported_Response_Unit=nM; Response=1; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Stroheker et al. 2004; 15110097; 10.1016/j.fct.2004.01.012; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LEL | 10 | nM | - | - | - | In Vitro; AR Transactivation-Antagonist | sheet=Data_invitro; excel_row=15018; Record_ID=endocrine_invitro_4254; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Transactivation-Antagonist; Endpoint=LEL; Reported_Response=10; Reported_Response_Unit=nM; Response=10; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LEL | 500 | nM | - | - | - | In Vitro; AR Transactivation-Agonist | sheet=Data_invitro; excel_row=10847; Record_ID=endocrine_invitro_3655; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Transactivation-Agonist; Endpoint=LEL; Reported_Response=500; Reported_Response_Unit=nM; Response=500; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LEL | 10000 | nM | - | - | - | In Vitro; AR Transactivation-Agonist | sheet=Data_invitro; excel_row=10384; Record_ID=endocrine_invitro_3665; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Transactivation-Agonist; Endpoint=LEL; Reported_Response=10000; Reported_Response_Unit=nM; Response=10000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Stroheker et al. 2004; 15110097; 10.1016/j.fct.2004.01.012; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LEL | 100000 | nM | - | - | - | In Vitro; AR Transactivation-Antagonist | sheet=Data_invitro; excel_row=15043; Record_ID=endocrine_invitro_4238; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Transactivation-Antagonist; Endpoint=LEL; Reported_Response=100000; Reported_Response_Unit=nM; Response=100000; Response_Unit=nM; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Gao et al. 2004; 15042621; 10.1002/pros.10375; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 1 | mg/kg bw/day | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 18; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=838; Record_ID=endocrine_invivo_128; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=1; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=80; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol B; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 2.5 | mg/kg bw/day | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 19 to 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=5 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=830; Record_ID=endocrine_invivo_120; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=2.5; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Ap; Strain=Alderley Park; Sex=Female; Route=Subcutaneous; Maximum_Dose=10; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Experiment 2; Reference=Tinwell and Ashby 2004; 15064164; 10.1289/ehp.6831|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 5 | mg/kg bw/day | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=842; Record_ID=endocrine_invivo_131; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=5; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Crj:CD(SD); Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=20; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Reference=Yamasaki et al. 2002; 12415423; 10.1007/s00204-002-0383-1|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 10 | mg/kg bw/day | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 19 to 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=2 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=825; Record_ID=endocrine_invivo_145; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=10; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Ap; Strain=Alderley Park; Sex=Female; Route=Subcutaneous; Maximum_Dose=10; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Experiment 6; Reference=Tinwell and Ashby 2004; 15064164; 10.1289/ehp.6831|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 15 | mg/kg bw/day | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=821; Record_ID=endocrine_invivo_135; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=15; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Subcutaneous; Maximum_Dose=80; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol C; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 20 | mg/kg bw/day | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=819; Record_ID=endocrine_invivo_132; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=20; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Crj:CD(SD); Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=20; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Reference=Yamasaki et al. 2002; 12415423; 10.1007/s00204-002-0383-1|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 35 | mg/kg bw/day | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=847; Record_ID=endocrine_invivo_136; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=35; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Crl:CD(SD)IGS BR; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Subcutaneous; Maximum_Dose=50; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol C; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 60 | mg/kg bw/day | Rat | Oral | Treatment_Duration=7 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=828; Record_ID=endocrine_invivo_118; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=60; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Crl:CD(SD)IGS BR; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Oral; Maximum_Dose=300; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol D; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 100 | mg/kg bw/day | Rat | Oral | Treatment_Duration=4 days; Age_at_First_Dose=PND 22; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=4 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=820; Record_ID=endocrine_invivo_127; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=100; Response_Unit=mg/kg/day; Species=Rat; Reported_Strain=Wistar; Strain=Wistar; Sex=Female; Route=Oral; Maximum_Dose=200; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Estradiol; Reference=Stroheker et al. 2003; 12849853; 10.1016/s0890-6238(03)00044-3|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | LOEL | 200 | mg/kg bw/day | Mouse | Oral | Treatment_Duration=7 days; Age_at_First_Dose=PND 56; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=2 weeks; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=4 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=831; Record_ID=endocrine_invivo_122; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=LOEL; Response=200; Response_Unit=mg/kg/day; Species=Mouse; Reported_Strain=C57BL/6J; Strain=C57BL/6; Sex=Female (ovariectomized); Route=Oral; Maximum_Dose=600; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Reference=Ohta et al. 2012; 23037998; 10.2131/jts.37.879|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Model Score | 0 | unitless | - | - | - | ARPathway2016; AR Pathway Model, Antagonist | sheet=Integrated_approaches; excel_row=9954; RecordID=ARPathway2016_1213; DatasetName=ARPathway2016; DTXSID=DTXSID5022308; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Model Score | 0.538 | unitless | - | - | - | ERPathway2016; ER Pathway Model, Agonist | sheet=Integrated_approaches; excel_row=9960; RecordID=ERPathway2016_156; DatasetName=ERPathway2016; DTXSID=DTXSID5022308; Assay=ER Pathway Model, Agonist; Endpoint=Model Score; Response=0.538; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | PC50 | 24.5 | nM | - | - | - | In Vitro; ER Transactivation-Agonist (STTA Assay) | sheet=Data_invitro; excel_row=16526; Record_ID=endocrine_invitro_4456; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=ER Transactivation-Agonist (STTA Assay); Endpoint=PC50; Reported_Response=2.4500000000000001E-8; Reported_Response_Unit=M; Conversion_Factor=1000000000; Conversion_Factor_Value=1000000000; Converted_Response=24.5; Converted_Response_Unit=nM; Response=24.5; Response_Unit=nM; Reference=|OECD TG 455; https://www.oecd.org/env/test-no-455-performance-based-test-guideline-for-stably-transfected-transactivation-in-vitro-assays-to-detect-estrogen-receptor-9789264265295-en.htm; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | RBA | 0.0029 | unitless | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=2076; Record_ID=endocrine_invitro_227; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=RBA; Reported_Response=2.8999999999999998E-3; Reported_Response_Unit=Unitless; Response=0.0029; Response_Unit=Unitless; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Freyberger and Ahr 2004; 14751668; 10.1016/j.tox.2003.09.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | RBA | 0.0036 | unitless | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=2077; Record_ID=endocrine_invitro_122; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=RBA; Reported_Response=3.5999999999999999E-3; Reported_Response_Unit=Unitless; Response=0.0036; Response_Unit=Unitless; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Fang et al. 2003; 14565775; 10.1021/tx030011g; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | RBA | 0.003631 | unitless | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=1896; Record_ID=endocrine_invitro_655; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=RBA; Reported_Response=-2.44; Reported_Response_Unit=Unitless; Conversion_Factor=Anti-log; Converted_Response=3.630780547701011E-3; Converted_Response_Unit=Unitless; Response=0.003631; Response_Unit=Unitless; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Hong et al. 2003; 14758981; 10.1080/10629360310001623962; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | RBA | 0.0039 | unitless | - | - | - | In Vitro; AR Binding | sheet=Data_invitro; excel_row=2075; Record_ID=endocrine_invitro_226; Data_Type=In Vitro; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=AR Binding; Endpoint=RBA; Reported_Response=3.8999999999999998E-3; Reported_Response_Unit=Unitless; Response=0.0039; Response_Unit=Unitless; Reference=Kleinstreuer et al. 2016; 27933809; 10.1021/acs.chemrestox.6b00347|Freyberger and Ahr 2004; 14751668; 10.1016/j.tox.2003.09.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 118 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 18; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=491; Record_ID=endocrine_invivo_128; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=118; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=80; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol B; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 120 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 19 to 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=5 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=483; Record_ID=endocrine_invivo_120; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=120; Response_Unit=%; Species=Rat; Reported_Strain=Ap; Strain=Alderley Park; Sex=Female; Route=Subcutaneous; Maximum_Dose=10; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Experiment 2; Reference=Tinwell and Ashby 2004; 15064164; 10.1289/ehp.6831|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 136 | % | Rat | Oral | Treatment_Duration=3 days; Age_at_First_Dose=PND 18; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=480; Record_ID=endocrine_invivo_117; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=136; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female; Route=Oral; Maximum_Dose=500; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol A; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 142 | % | Rat | Oral | Treatment_Duration=3 days; Age_at_First_Dose=PND 18; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=519; Record_ID=endocrine_invivo_144; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=142; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female; Route=Oral; Maximum_Dose=500; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol A; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 148 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 18; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=487; Record_ID=endocrine_invivo_125; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=148; Response_Unit=%; Species=Rat; Reported_Strain=Crl:CD(SD)IGS BR; Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=50; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol B; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 153 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=471; Record_ID=endocrine_invivo_135; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=153; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Subcutaneous; Maximum_Dose=80; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol C; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 156 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=506; Record_ID=endocrine_invivo_136; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=156; Response_Unit=%; Species=Rat; Reported_Strain=Crl:CD(SD)IGS BR; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Subcutaneous; Maximum_Dose=50; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol C; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 157 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=473; Record_ID=endocrine_invivo_137; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=157; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Subcutaneous; Maximum_Dose=80; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol C; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 161 | % | Rat | Oral | Treatment_Duration=3 days; Age_at_First_Dose=PND 18; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=509; Record_ID=endocrine_invivo_138; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=161; Response_Unit=%; Species=Rat; Reported_Strain=Alpk:ApfSD; Strain=Alderley Park; Sex=Female; Route=Oral; Maximum_Dose=500; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol A; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 167 | % | Rat | Subcutaneous | Treatment_Duration=7 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=477; Record_ID=endocrine_invivo_142; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=167; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Subcutaneous; Maximum_Dose=80; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol D; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 179 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 18; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=468; Record_ID=endocrine_invivo_130; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=179; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=80; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol B; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 180 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 19 to 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=2 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=478; Record_ID=endocrine_invivo_145; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=180; Response_Unit=%; Species=Rat; Reported_Strain=Ap; Strain=Alderley Park; Sex=Female; Route=Subcutaneous; Maximum_Dose=10; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Experiment 6; Reference=Tinwell and Ashby 2004; 15064164; 10.1289/ehp.6831|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 183 | % | Rat | Oral | Treatment_Duration=7 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=481; Record_ID=endocrine_invivo_118; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=183; Response_Unit=%; Species=Rat; Reported_Strain=Crl:CD(SD)IGS BR; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Oral; Maximum_Dose=300; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol D; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 200 | % | Rat | Oral | Treatment_Duration=4 days; Age_at_First_Dose=PND 22; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=4 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=466; Record_ID=endocrine_invivo_127; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=200; Response_Unit=%; Species=Rat; Reported_Strain=Wistar; Strain=Wistar; Sex=Female; Route=Oral; Maximum_Dose=200; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Estradiol; Reference=Stroheker et al. 2003; 12849853; 10.1016/s0890-6238(03)00044-3|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 206 | % | Rat | Subcutaneous | Treatment_Duration=7 days; Age_at_First_Dose=PND 56 to 84; Age_Ovariectomized_or_Castrated=6 weeks; Time_Elapsed_Between_Surgery_and_Treatment=14 to 28 days; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=514; Record_ID=endocrine_invivo_141; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=206; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD)IGS; Strain=Sprague-Dawley; Sex=Female (ovariectomized); Route=Subcutaneous; Maximum_Dose=80; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol D; Reference=Kanno et al. 2003; 12948896; 10.1289/ehp.5780|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 210 | % | Rat | Oral | Treatment_Duration=3 days; Age_at_First_Dose=PND 19; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=4 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=476; Record_ID=endocrine_invivo_140; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=210; Response_Unit=%; Species=Rat; Reported_Strain=SD; Strain=Sprague-Dawley; Sex=Female; Route=Oral; Maximum_Dose=750; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Estradiol; Reference=Zhang et al. 2008; 19239007; Not available|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 230 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=495; Record_ID=endocrine_invivo_131; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=230; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD); Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=20.0; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Reference=Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 240 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 19 to 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=511; Record_ID=endocrine_invivo_139; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=240; Response_Unit=%; Species=Rat; Reported_Strain=Ap; Strain=Alderley Park; Sex=Female; Route=Subcutaneous; Maximum_Dose=50; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Experiment 1; Reference=Tinwell and Ashby 2004; 15064164; 10.1289/ehp.6831|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 245 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 20 to 22; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=497; Record_ID=endocrine_invivo_133; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=245; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD); Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=200; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Estradiol; Reference=Yamasaki et al. 2002; 11750080; 10.1016/s0300-483x(01)00505-4|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 249 | % | Rat | Oral | Treatment_Duration=3 days; Age_at_First_Dose=PND 18; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3+ | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=502; Record_ID=endocrine_invivo_134; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=249; Response_Unit=%; Species=Rat; Reported_Strain=Crl:CD(SD)IGS BR; Strain=Sprague-Dawley; Sex=Female; Route=Oral; Maximum_Dose=300.0; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Additional_Information=Protocol A; Reference=Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 250 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=469; Record_ID=endocrine_invivo_132; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=250; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD); Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=20; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Reference=Yamasaki et al. 2002; 12415423; 10.1007/s00204-002-0383-1|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
| NTP_ICE_endocrine | Uterine weight increase vs control | 260 | % | Rat | Subcutaneous | Treatment_Duration=3 days; Age_at_First_Dose=PND 20; Time_Elapsed_Between_Last_Dose_and_Necropsy=24 hours; Number_of_Doses_Tested=3 | In Vivo; Uterotrophic-Agonist | sheet=Data_invivo; excel_row=485; Record_ID=endocrine_invivo_123; Data_Type=In Vivo; Mixture=Chemical; DTXSID=DTXSID5022308; Assay=Uterotrophic-Agonist; Endpoint=Uterine weight increase vs control; Response=260; Response_Unit=%; Species=Rat; Reported_Strain=Crj:CD(SD); Strain=Sprague-Dawley; Sex=Female; Route=Subcutaneous; Maximum_Dose=20; Maximum_Dose_Units=mg/kg/day; Reference_Hormone=Ethinylestradiol; Reference=Yamasaki et al. 2002; 12415423; 10.1007/s00204-002-0383-1|Kleinstreuer et al. 2016; 26431337; 10.1289/ehp.1510183; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID5022308; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID5022308 |
SCCS_vision_codex 84 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =0.02 | % | rat | oral | developmental | reproductive toxicity | {"dose":"(2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL.","effect":"alsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg","page":71,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_028"} |
| SCCS_vision_codex | NOAEL | =0.02 | % | rat | oral | developmental | reproductive toxicity | {"dose":"(2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL.","effect":"alsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg","page":71,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_028"} |
| SCCS_vision_codex | NOAEL | =0.02 | % | rat | oral | developmental | reproductive toxicity | {"dose":"(2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL.","effect":"alsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg","page":71,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_028"} |
| SCCS_vision_codex | NOAEL | =0.02 | % | rat | oral | developmental | reproductive toxicity | {"dose":"(2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL.","effect":"alsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg","page":71,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_028"} |
| SCCS_vision_codex | NOAEL | =0.3 | % | rat | - | developmental | reproductive toxicity | {"dose":"In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","effect":"nt, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to da","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_008"} |
| SCCS_vision_codex | NOAEL | =0.3 | % | rat | - | developmental | reproductive toxicity | {"dose":"In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","effect":"nt, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to da","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_008"} |
| SCCS_vision_codex | NOAEL | =0.3 | % | rat | - | developmental | reproductive toxicity | {"dose":"In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","effect":"nt, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to da","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_008"} |
| SCCS_vision_codex | NOAEL | =0.3 | % | rat | - | developmental | reproductive toxicity | {"dose":"In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","effect":"nt, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to da","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_008"} |
| SCCS_vision_codex | NOAEL | =4 | mg/kg bw/day | - | oral | 2 weeks | NOAEL study | {"dose":"Testis weights were unaffected by either dose of genistein.","effect":"ornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein Lamartiniere et al., 2002 Guidelines/Guidances: / Test item: daidzein Purity: 98.5% (HPLC) Impurity: 1.5 % Methanol Vehicle: feed (phytoestrogen-free AIN-76A diet) Route of exposure: oral (feed) Duration of exposure: 2 weeks before breedin","page":32,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_005"} |
| SCCS_vision_codex | NOAEL | =4 | mg/kg bw/day | - | oral | 2 weeks | NOAEL study | {"dose":"Testis weights were unaffected by either dose of genistein.","effect":"ornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein Lamartiniere et al., 2002 Guidelines/Guidances: / Test item: daidzein Purity: 98.5% (HPLC) Impurity: 1.5 % Methanol Vehicle: feed (phytoestrogen-free AIN-76A diet) Route of exposure: oral (feed) Duration of exposure: 2 weeks before breedin","page":32,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_005"} |
| SCCS_vision_codex | NOAEL | =4 | mg/kg bw/day | - | oral | 2 weeks | NOAEL study | {"dose":"Testis weights were unaffected by either dose of genistein.","effect":"ornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein Lamartiniere et al., 2002 Guidelines/Guidances: / Test item: daidzein Purity: 98.5% (HPLC) Impurity: 1.5 % Methanol Vehicle: feed (phytoestrogen-free AIN-76A diet) Route of exposure: oral (feed) Duration of exposure: 2 weeks before breedin","page":32,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_005"} |
| SCCS_vision_codex | NOAEL | =4 | mg/kg bw/day | - | oral | 2 weeks | NOAEL study | {"dose":"Testis weights were unaffected by either dose of genistein.","effect":"ornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein Lamartiniere et al., 2002 Guidelines/Guidances: / Test item: daidzein Purity: 98.5% (HPLC) Impurity: 1.5 % Methanol Vehicle: feed (phytoestrogen-free AIN-76A diet) Route of exposure: oral (feed) Duration of exposure: 2 weeks before breedin","page":32,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_005"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | human | - | - | reproductive toxicity | {"dose":"Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL.","effect":"t risks for human health. SCCS comment This study is described from the open literature and the original study report is not available to the SCCS. It is not a guideline study and not all parameters usually investigated in guideline studies were addressed. Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. With this statement SCCS concurs with the Nordic Council report of Ministers (2020) and with the NTP-CERHR (2010) as both consider thtn even if the study by Talsness et al. (2015) may be potentially relevant, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_007"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg | rat | oral | - | reproductive toxicity | {"dose":"Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for th...","effect":"oute. Moreover, a significant skin penetration of daidzein would be considered because the SCCS considered appropriate to use the default value of 50% skin penetration (the submitter had proposed 100%). Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, derived from Talsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances","page":71,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_026"} |
| SCCS_vision_codex | NOAEL | =5 | - | rat | - | 30 days | NOAEL study | {"effect":"Unlabeled table on page 153: Romero et al., 2019 | Daidzein | Wistar rats | female | ovariecto mized | sc | 5 mg/k g | 30 days | estradiol | In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increased uterine and vaginal epithelium in proestrus and diestrus periods, increased uterine and vaginal relative weights during diestrus, and decreased serum progesterone during proestrus All these effects were similar to those of DAI but lower than E2- induced effects. In OVX females, DAI decreased body weight, induced lordosis, | These results indicate that, in gonadally intact females, LEU (and DAI) can produce antiestrogenic effects in sexual behavior but estrogenic effects on uterine and vaginal weight and epithelia, without modifying serum levels of E2. In OVX females, in total absence of endogenous E2, LEU induced estrogenic effects on vaginal weight and epithelia, as | LOEL = 5mk/kg sc","page":153,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_050"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | human | - | - | reproductive toxicity | {"dose":"Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL.","effect":"t risks for human health. SCCS comment This study is described from the open literature and the original study report is not available to the SCCS. It is not a guideline study and not all parameters usually investigated in guideline studies were addressed. Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. With this statement SCCS concurs with the Nordic Council report of Ministers (2020) and with the NTP-CERHR (2010) as both consider thtn even if the study by Talsness et al. (2015) may be potentially relevant, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_007"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg | rat | oral | - | reproductive toxicity | {"dose":"Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for th...","effect":"oute. Moreover, a significant skin penetration of daidzein would be considered because the SCCS considered appropriate to use the default value of 50% skin penetration (the submitter had proposed 100%). Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, derived from Talsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances","page":71,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_026"} |
| SCCS_vision_codex | NOAEL | =5 | - | rat | - | 30 days | NOAEL study | {"effect":"Unlabeled table on page 153: Romero et al., 2019 | Daidzein | Wistar rats | female | ovariecto mized | sc | 5 mg/k g | 30 days | estradiol | In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increased uterine and vaginal epithelium in proestrus and diestrus periods, increased uterine and vaginal relative weights during diestrus, and decreased serum progesterone during proestrus All these effects were similar to those of DAI but lower than E2- induced effects. In OVX females, DAI decreased body weight, induced lordosis, | These results indicate that, in gonadally intact females, LEU (and DAI) can produce antiestrogenic effects in sexual behavior but estrogenic effects on uterine and vaginal weight and epithelia, without modifying serum levels of E2. In OVX females, in total absence of endogenous E2, LEU induced estrogenic effects on vaginal weight and epithelia, as | LOEL = 5mk/kg sc","page":153,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_050"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | human | - | - | reproductive toxicity | {"dose":"Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL.","effect":"t risks for human health. SCCS comment This study is described from the open literature and the original study report is not available to the SCCS. It is not a guideline study and not all parameters usually investigated in guideline studies were addressed. Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. With this statement SCCS concurs with the Nordic Council report of Ministers (2020) and with the NTP-CERHR (2010) as both consider thtn even if the study by Talsness et al. (2015) may be potentially relevant, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_007"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg | rat | oral | - | reproductive toxicity | {"dose":"Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for th...","effect":"oute. Moreover, a significant skin penetration of daidzein would be considered because the SCCS considered appropriate to use the default value of 50% skin penetration (the submitter had proposed 100%). Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, derived from Talsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances","page":71,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_026"} |
| SCCS_vision_codex | NOAEL | =5 | - | rat | - | 30 days | NOAEL study | {"effect":"Unlabeled table on page 153: Romero et al., 2019 | Daidzein | Wistar rats | female | ovariecto mized | sc | 5 mg/k g | 30 days | estradiol | In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increased uterine and vaginal epithelium in proestrus and diestrus periods, increased uterine and vaginal relative weights during diestrus, and decreased serum progesterone during proestrus All these effects were similar to those of DAI but lower than E2- induced effects. In OVX females, DAI decreased body weight, induced lordosis, | These results indicate that, in gonadally intact females, LEU (and DAI) can produce antiestrogenic effects in sexual behavior but estrogenic effects on uterine and vaginal weight and epithelia, without modifying serum levels of E2. In OVX females, in total absence of endogenous E2, LEU induced estrogenic effects on vaginal weight and epithelia, as | LOEL = 5mk/kg sc","page":153,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_050"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | human | - | - | reproductive toxicity | {"dose":"Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL.","effect":"t risks for human health. SCCS comment This study is described from the open literature and the original study report is not available to the SCCS. It is not a guideline study and not all parameters usually investigated in guideline studies were addressed. Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. With this statement SCCS concurs with the Nordic Council report of Ministers (2020) and with the NTP-CERHR (2010) as both consider thtn even if the study by Talsness et al. (2015) may be potentially relevant, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_007"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg | rat | oral | - | reproductive toxicity | {"dose":"Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for th...","effect":"oute. Moreover, a significant skin penetration of daidzein would be considered because the SCCS considered appropriate to use the default value of 50% skin penetration (the submitter had proposed 100%). Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, derived from Talsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances","page":71,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_026"} |
| SCCS_vision_codex | NOAEL | =5 | - | rat | - | 30 days | NOAEL study | {"effect":"Unlabeled table on page 153: Romero et al., 2019 | Daidzein | Wistar rats | female | ovariecto mized | sc | 5 mg/k g | 30 days | estradiol | In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increased uterine and vaginal epithelium in proestrus and diestrus periods, increased uterine and vaginal relative weights during diestrus, and decreased serum progesterone during proestrus All these effects were similar to those of DAI but lower than E2- induced effects. In OVX females, DAI decreased body weight, induced lordosis, | These results indicate that, in gonadally intact females, LEU (and DAI) can produce antiestrogenic effects in sexual behavior but estrogenic effects on uterine and vaginal weight and epithelia, without modifying serum levels of E2. In OVX females, in total absence of endogenous E2, LEU induced estrogenic effects on vaginal weight and epithelia, as | LOEL = 5mk/kg sc","page":153,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_050"} |
| SCCS_vision_codex | NOAEL | =7.4 | mg/kg bw | human | oral | - | NOAEL study | {"dose":"Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...","effect":"______________________ _______________________________________________________________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed a","page":70,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_020"} |
| SCCS_vision_codex | NOAEL | =7.4 | mg/kg bw | human | oral | - | NOAEL study | {"dose":"Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...","effect":"______________________ _______________________________________________________________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed a","page":70,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_020"} |
| SCCS_vision_codex | NOAEL | =7.4 | mg/kg bw | human | oral | - | NOAEL study | {"dose":"Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...","effect":"______________________ _______________________________________________________________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed a","page":70,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_020"} |
| SCCS_vision_codex | NOAEL | =7.4 | mg/kg bw | human | oral | - | NOAEL study | {"dose":"Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...","effect":"______________________ _______________________________________________________________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed a","page":70,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_020"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw | - | oral | - | NOAEL study | {"dose":"Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al.","effect":"Unlabeled table on page 119: Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al. (2004)","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_041"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw | - | oral | - | NOAEL study | {"dose":"Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al.","effect":"Unlabeled table on page 119: Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al. (2004)","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_041"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw | - | oral | - | NOAEL study | {"dose":"Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al.","effect":"Unlabeled table on page 119: Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al. (2004)","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_041"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw | - | oral | - | NOAEL study | {"dose":"Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al.","effect":"Unlabeled table on page 119: Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al. (2004)","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_041"} |
| SCCS_vision_codex | NOAEL | =16 | mg/kg bw/d | pig | oral | Chronic | carcinogenicity | {"dose":"Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d.","effect":"inal version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 28 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, a variety of toxicologically relevant parameters have been investigated in the study, and adverse effects are observed at 400 mg/daidzein/kg diet and a NOAEL of 200 mg daidzein/kg diet. Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d. 3.3.4.2.3 Chronic (> 12 months) toxicity Under the conditions of a 2-year feed study with continuous exposure to the test compound from conception through termination (F1C), there was no evidence of carcinogenic activit","page":28,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_002"} |
| SCCS_vision_codex | NOAEL | =16 | mg/kg bw/d | pig | oral | Chronic | carcinogenicity | {"dose":"Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d.","effect":"inal version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 28 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, a variety of toxicologically relevant parameters have been investigated in the study, and adverse effects are observed at 400 mg/daidzein/kg diet and a NOAEL of 200 mg daidzein/kg diet. Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d. 3.3.4.2.3 Chronic (> 12 months) toxicity Under the conditions of a 2-year feed study with continuous exposure to the test compound from conception through termination (F1C), there was no evidence of carcinogenic activit","page":28,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_002"} |
| SCCS_vision_codex | NOAEL | =16 | mg/kg bw/d | pig | oral | Chronic | carcinogenicity | {"dose":"Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d.","effect":"inal version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 28 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, a variety of toxicologically relevant parameters have been investigated in the study, and adverse effects are observed at 400 mg/daidzein/kg diet and a NOAEL of 200 mg daidzein/kg diet. Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d. 3.3.4.2.3 Chronic (> 12 months) toxicity Under the conditions of a 2-year feed study with continuous exposure to the test compound from conception through termination (F1C), there was no evidence of carcinogenic activit","page":28,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_002"} |
| SCCS_vision_codex | NOAEL | =16 | mg/kg bw/d | pig | oral | Chronic | carcinogenicity | {"dose":"Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d.","effect":"inal version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 28 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, a variety of toxicologically relevant parameters have been investigated in the study, and adverse effects are observed at 400 mg/daidzein/kg diet and a NOAEL of 200 mg daidzein/kg diet. Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d. 3.3.4.2.3 Chronic (> 12 months) toxicity Under the conditions of a 2-year feed study with continuous exposure to the test compound from conception through termination (F1C), there was no evidence of carcinogenic activit","page":28,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_002"} |
| SCCS_vision_codex | NOAEL | =19 | mg/kg bw/d | rat | oral | - | reproductive toxicity | {"dose":"Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL.","effect":"________________________________________________________________ _______________________________________________________________________ 34 Otherwise, none of the daidzein doses had a significant effect on the weights and histomorphology of the female reproductive tract. SCCS comment This study is described in the open literature and the original study report is not available to the SCCS. Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL. Talsness et al., 2015 Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP Test item: daidzein (DZ) Purity: / Vehicle: 2% Corn starch Positive control: 17α-Ethinyl estradiol (EE) Purity / Vehicle: Peanut Oil Route of exposure: Oral - gavage Duration of exposure: GD 6 –GD 21 Doses: DZ: 0, 5 and 60 mg/kg bw/d; EE: 0.0002 mg/kg bw/d Experimental animals: Species: Rats Strain: Sprague Dawley Sex: Gravid female Animal numbers: 6 groups of 8-10 females (","page":34,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_006"} |
| SCCS_vision_codex | NOAEL | =19 | mg/kg bw/d | rat | oral | - | reproductive toxicity | {"dose":"Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL.","effect":"________________________________________________________________ _______________________________________________________________________ 34 Otherwise, none of the daidzein doses had a significant effect on the weights and histomorphology of the female reproductive tract. SCCS comment This study is described in the open literature and the original study report is not available to the SCCS. Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL. Talsness et al., 2015 Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP Test item: daidzein (DZ) Purity: / Vehicle: 2% Corn starch Positive control: 17α-Ethinyl estradiol (EE) Purity / Vehicle: Peanut Oil Route of exposure: Oral - gavage Duration of exposure: GD 6 –GD 21 Doses: DZ: 0, 5 and 60 mg/kg bw/d; EE: 0.0002 mg/kg bw/d Experimental animals: Species: Rats Strain: Sprague Dawley Sex: Gravid female Animal numbers: 6 groups of 8-10 females (","page":34,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_006"} |
| SCCS_vision_codex | NOAEL | =19 | mg/kg bw/d | rat | oral | - | reproductive toxicity | {"dose":"Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL.","effect":"________________________________________________________________ _______________________________________________________________________ 34 Otherwise, none of the daidzein doses had a significant effect on the weights and histomorphology of the female reproductive tract. SCCS comment This study is described in the open literature and the original study report is not available to the SCCS. Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL. Talsness et al., 2015 Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP Test item: daidzein (DZ) Purity: / Vehicle: 2% Corn starch Positive control: 17α-Ethinyl estradiol (EE) Purity / Vehicle: Peanut Oil Route of exposure: Oral - gavage Duration of exposure: GD 6 –GD 21 Doses: DZ: 0, 5 and 60 mg/kg bw/d; EE: 0.0002 mg/kg bw/d Experimental animals: Species: Rats Strain: Sprague Dawley Sex: Gravid female Animal numbers: 6 groups of 8-10 females (","page":34,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_006"} |
| SCCS_vision_codex | NOAEL | =19 | mg/kg bw/d | rat | oral | - | reproductive toxicity | {"dose":"Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL.","effect":"________________________________________________________________ _______________________________________________________________________ 34 Otherwise, none of the daidzein doses had a significant effect on the weights and histomorphology of the female reproductive tract. SCCS comment This study is described in the open literature and the original study report is not available to the SCCS. Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL. Talsness et al., 2015 Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP Test item: daidzein (DZ) Purity: / Vehicle: 2% Corn starch Positive control: 17α-Ethinyl estradiol (EE) Purity / Vehicle: Peanut Oil Route of exposure: Oral - gavage Duration of exposure: GD 6 –GD 21 Doses: DZ: 0, 5 and 60 mg/kg bw/d; EE: 0.0002 mg/kg bw/d Experimental animals: Species: Rats Strain: Sprague Dawley Sex: Gravid female Animal numbers: 6 groups of 8-10 females (","page":34,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_006"} |
| SCCS_vision_codex | NOAEL | =20 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 119: ↓Weight at vaginal opening, | 20 | 87 | 55 | 36 | 59 | 36","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_043"} |
| SCCS_vision_codex | NOAEL | =20 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 119: ↓Weight at vaginal opening, | 20 | 87 | 55 | 36 | 59 | 36","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_043"} |
| SCCS_vision_codex | NOAEL | =20 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 119: ↓Weight at vaginal opening, | 20 | 87 | 55 | 36 | 59 | 36","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_043"} |
| SCCS_vision_codex | NOAEL | =20 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 119: ↓Weight at vaginal opening, | 20 | 87 | 55 | 36 | 59 | 36","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_043"} |
| SCCS_vision_codex | NOAEL | =25 | % | human | oral | - | NOAEL study | {"dose":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route:","effect":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the","page":70,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_023"} |
| SCCS_vision_codex | NOAEL | =25 | % | human | oral | - | NOAEL study | {"dose":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route:","effect":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the","page":70,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_023"} |
| SCCS_vision_codex | NOAEL | =25 | % | human | oral | - | NOAEL study | {"dose":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route:","effect":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the","page":70,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_023"} |
| SCCS_vision_codex | NOAEL | =25 | % | human | oral | - | NOAEL study | {"dose":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route:","effect":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the","page":70,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_023"} |
| SCCS_vision_codex | NOAEL | =35 | mg/kg | rat | - | 3 months | reproductive toxicity | {"dose":"SCCS comment In this study, 35 mg/kg could be considered as a NOAEL.","effect":"changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remained unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. In conclusion, compared to GEN, DAI did not promote events associated with the endometrial cell proliferation. SCCS comment In this study, 35 mg/kg could be considered as a NOAEL. In the study from Sergio et al. (2019), the authors aimed to investigate different female reproductive variables of leucaena and daidzein in ovariectomized or ovary intact rats. Daidzein was administered subcutaneously to ovariectomized or ovary intact Wistar rats (3 months old) at the dose of 5 mg/kg during 30 days. Estradiol was used as a positive control. In intact females, daidzein disrupted the estrous cycle and female sexual behaviour, decreased the number of follicles and corpora lutea, increased uterine","page":67,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_018"} |
| SCCS_vision_codex | NOAEL | =35 | mg/kg | rat | - | 3 months | reproductive toxicity | {"dose":"SCCS comment In this study, 35 mg/kg could be considered as a NOAEL.","effect":"changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remained unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. In conclusion, compared to GEN, DAI did not promote events associated with the endometrial cell proliferation. SCCS comment In this study, 35 mg/kg could be considered as a NOAEL. In the study from Sergio et al. (2019), the authors aimed to investigate different female reproductive variables of leucaena and daidzein in ovariectomized or ovary intact rats. Daidzein was administered subcutaneously to ovariectomized or ovary intact Wistar rats (3 months old) at the dose of 5 mg/kg during 30 days. Estradiol was used as a positive control. In intact females, daidzein disrupted the estrous cycle and female sexual behaviour, decreased the number of follicles and corpora lutea, increased uterine","page":67,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_018"} |
| SCCS_vision_codex | NOAEL | =35 | mg/kg | rat | - | 3 months | reproductive toxicity | {"dose":"SCCS comment In this study, 35 mg/kg could be considered as a NOAEL.","effect":"changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remained unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. In conclusion, compared to GEN, DAI did not promote events associated with the endometrial cell proliferation. SCCS comment In this study, 35 mg/kg could be considered as a NOAEL. In the study from Sergio et al. (2019), the authors aimed to investigate different female reproductive variables of leucaena and daidzein in ovariectomized or ovary intact rats. Daidzein was administered subcutaneously to ovariectomized or ovary intact Wistar rats (3 months old) at the dose of 5 mg/kg during 30 days. Estradiol was used as a positive control. In intact females, daidzein disrupted the estrous cycle and female sexual behaviour, decreased the number of follicles and corpora lutea, increased uterine","page":67,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_018"} |
| SCCS_vision_codex | NOAEL | =35 | mg/kg | rat | - | 3 months | reproductive toxicity | {"dose":"SCCS comment In this study, 35 mg/kg could be considered as a NOAEL.","effect":"changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remained unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. In conclusion, compared to GEN, DAI did not promote events associated with the endometrial cell proliferation. SCCS comment In this study, 35 mg/kg could be considered as a NOAEL. In the study from Sergio et al. (2019), the authors aimed to investigate different female reproductive variables of leucaena and daidzein in ovariectomized or ovary intact rats. Daidzein was administered subcutaneously to ovariectomized or ovary intact Wistar rats (3 months old) at the dose of 5 mg/kg during 30 days. Estradiol was used as a positive control. In intact females, daidzein disrupted the estrous cycle and female sexual behaviour, decreased the number of follicles and corpora lutea, increased uterine","page":67,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_018"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg/day | - | - | - | NOAEL study | {"dose":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups.","effect":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein L","page":32,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_003"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg/day | - | - | - | NOAEL study | {"dose":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups.","effect":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein L","page":32,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_003"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg/day | - | - | - | NOAEL study | {"dose":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups.","effect":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein L","page":32,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_003"} |
| SCCS_vision_codex | NOAEL | =40 | mg/kg/day | - | - | - | NOAEL study | {"dose":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups.","effect":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein L","page":32,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_003"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg/day | - | - | 13 weeks | reproductive toxicity | {"dose":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test.","effect":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test. When comparing the NOELs/LOELs of genistein for different exposure durations there was no apparent difference after 4 and 13 weeks. The treatment-related findings would be expected to occur with a compound with intrinsic estrogenic activity. The no observed adverse effect level (NOAEL) of genistein is considered to be between 5 and 50 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. In a clinical trial by Bitto et al. (2010), genistein aglycone (54 mg) or placebo was given daily to osteopenic post-menopausal women for 24 months. A sub-cohort then continued therapy for an additional 12 months to evaluate the thyroid (THR α and THR β) and retinoid (RAR α, RAR γ, and RXR α) hormone receptors, mRNAs and the levels of thyro","page":60,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_016"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg/day | - | - | 13 weeks | reproductive toxicity | {"dose":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test.","effect":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test. When comparing the NOELs/LOELs of genistein for different exposure durations there was no apparent difference after 4 and 13 weeks. The treatment-related findings would be expected to occur with a compound with intrinsic estrogenic activity. The no observed adverse effect level (NOAEL) of genistein is considered to be between 5 and 50 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. In a clinical trial by Bitto et al. (2010), genistein aglycone (54 mg) or placebo was given daily to osteopenic post-menopausal women for 24 months. A sub-cohort then continued therapy for an additional 12 months to evaluate the thyroid (THR α and THR β) and retinoid (RAR α, RAR γ, and RXR α) hormone receptors, mRNAs and the levels of thyro","page":60,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_016"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg/day | - | - | 13 weeks | reproductive toxicity | {"dose":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test.","effect":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test. When comparing the NOELs/LOELs of genistein for different exposure durations there was no apparent difference after 4 and 13 weeks. The treatment-related findings would be expected to occur with a compound with intrinsic estrogenic activity. The no observed adverse effect level (NOAEL) of genistein is considered to be between 5 and 50 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. In a clinical trial by Bitto et al. (2010), genistein aglycone (54 mg) or placebo was given daily to osteopenic post-menopausal women for 24 months. A sub-cohort then continued therapy for an additional 12 months to evaluate the thyroid (THR α and THR β) and retinoid (RAR α, RAR γ, and RXR α) hormone receptors, mRNAs and the levels of thyro","page":60,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_016"} |
| SCCS_vision_codex | NOAEL | =50 | mg/kg/day | - | - | 13 weeks | reproductive toxicity | {"dose":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test.","effect":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test. When comparing the NOELs/LOELs of genistein for different exposure durations there was no apparent difference after 4 and 13 weeks. The treatment-related findings would be expected to occur with a compound with intrinsic estrogenic activity. The no observed adverse effect level (NOAEL) of genistein is considered to be between 5 and 50 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. In a clinical trial by Bitto et al. (2010), genistein aglycone (54 mg) or placebo was given daily to osteopenic post-menopausal women for 24 months. A sub-cohort then continued therapy for an additional 12 months to evaluate the thyroid (THR α and THR β) and retinoid (RAR α, RAR γ, and RXR α) hormone receptors, mRNAs and the levels of thyro","page":60,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_016"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | pig | oral | 28-day | repeated dose toxicity | {"dose":"However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein.","effect":"SCCS/1641/22 Final version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 27 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein. 3.3.4.2.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline/Guidance: / Species/Strain: crossbred [(Large White × Landrace) × Duroc] weaned pigs Group size: 12/sex/dose Test item: daidzein Purity: 98% Control: NRC (1998) standard commercial feed without any soy source Route of exposure: Oral, diet Duration: 70 days Doses: 0, 40, 200 and 400 mg daidzein/kg diet Study period: not stated, publication submitted in 2013 GLP:","page":27,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_001"} |
| SCCS_vision_codex | NOAEL | =100 | ppm | rat | oral | developmental | reproductive toxicity | {"dose":"SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.","effect":"iders that only the studies performed with pure daidzein are relevant for safety assessment as a cosmetic ingredient. SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these studies, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) in the current assessment.","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_010"} |
| SCCS_vision_codex | NOAEL | =100 | % | rat | oral | 90-day | NOAEL study | {"dose":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein ap...","effect":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 Low observed adverse effect level NOAEL mg/kg bw/d = 5 (90-day, sc, rat*) Bioavailability % = 100% Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety PODsys/SED = 385 * Retana Marquez, 2016 SCCS conclusion Although the Margin of Safety (MoS) calculated on the basis of oral exposure to daidzein comes out at marginally below 100 (96), it is much higher than 100 (385) when exposure via subcutaneous route is taken into account. Taking into view that the value of 25% used for oral bioavailability is very conservative, and that the subcu","page":72,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_032"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | pig | oral | 28-day | repeated dose toxicity | {"dose":"However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein.","effect":"SCCS/1641/22 Final version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 27 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein. 3.3.4.2.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline/Guidance: / Species/Strain: crossbred [(Large White × Landrace) × Duroc] weaned pigs Group size: 12/sex/dose Test item: daidzein Purity: 98% Control: NRC (1998) standard commercial feed without any soy source Route of exposure: Oral, diet Duration: 70 days Doses: 0, 40, 200 and 400 mg daidzein/kg diet Study period: not stated, publication submitted in 2013 GLP:","page":27,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_001"} |
| SCCS_vision_codex | NOAEL | =100 | ppm | rat | oral | developmental | reproductive toxicity | {"dose":"SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.","effect":"iders that only the studies performed with pure daidzein are relevant for safety assessment as a cosmetic ingredient. SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these studies, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) in the current assessment.","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_010"} |
| SCCS_vision_codex | NOAEL | =100 | % | rat | oral | 90-day | NOAEL study | {"dose":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein ap...","effect":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 Low observed adverse effect level NOAEL mg/kg bw/d = 5 (90-day, sc, rat*) Bioavailability % = 100% Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety PODsys/SED = 385 * Retana Marquez, 2016 SCCS conclusion Although the Margin of Safety (MoS) calculated on the basis of oral exposure to daidzein comes out at marginally below 100 (96), it is much higher than 100 (385) when exposure via subcutaneous route is taken into account. Taking into view that the value of 25% used for oral bioavailability is very conservative, and that the subcu","page":72,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_032"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | pig | oral | 28-day | repeated dose toxicity | {"dose":"However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein.","effect":"SCCS/1641/22 Final version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 27 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein. 3.3.4.2.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline/Guidance: / Species/Strain: crossbred [(Large White × Landrace) × Duroc] weaned pigs Group size: 12/sex/dose Test item: daidzein Purity: 98% Control: NRC (1998) standard commercial feed without any soy source Route of exposure: Oral, diet Duration: 70 days Doses: 0, 40, 200 and 400 mg daidzein/kg diet Study period: not stated, publication submitted in 2013 GLP:","page":27,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_001"} |
| SCCS_vision_codex | NOAEL | =100 | ppm | rat | oral | developmental | reproductive toxicity | {"dose":"SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.","effect":"iders that only the studies performed with pure daidzein are relevant for safety assessment as a cosmetic ingredient. SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these studies, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) in the current assessment.","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_010"} |
| SCCS_vision_codex | NOAEL | =100 | % | rat | oral | 90-day | NOAEL study | {"dose":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein ap...","effect":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 Low observed adverse effect level NOAEL mg/kg bw/d = 5 (90-day, sc, rat*) Bioavailability % = 100% Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety PODsys/SED = 385 * Retana Marquez, 2016 SCCS conclusion Although the Margin of Safety (MoS) calculated on the basis of oral exposure to daidzein comes out at marginally below 100 (96), it is much higher than 100 (385) when exposure via subcutaneous route is taken into account. Taking into view that the value of 25% used for oral bioavailability is very conservative, and that the subcu","page":72,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_032"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | pig | oral | 28-day | repeated dose toxicity | {"dose":"However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein.","effect":"SCCS/1641/22 Final version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 27 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein. 3.3.4.2.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline/Guidance: / Species/Strain: crossbred [(Large White × Landrace) × Duroc] weaned pigs Group size: 12/sex/dose Test item: daidzein Purity: 98% Control: NRC (1998) standard commercial feed without any soy source Route of exposure: Oral, diet Duration: 70 days Doses: 0, 40, 200 and 400 mg daidzein/kg diet Study period: not stated, publication submitted in 2013 GLP:","page":27,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_001"} |
| SCCS_vision_codex | NOAEL | =100 | ppm | rat | oral | developmental | reproductive toxicity | {"dose":"SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.","effect":"iders that only the studies performed with pure daidzein are relevant for safety assessment as a cosmetic ingredient. SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these studies, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) in the current assessment.","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_010"} |
| SCCS_vision_codex | NOAEL | =100 | % | rat | oral | 90-day | NOAEL study | {"dose":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein ap...","effect":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 Low observed adverse effect level NOAEL mg/kg bw/d = 5 (90-day, sc, rat*) Bioavailability % = 100% Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety PODsys/SED = 385 * Retana Marquez, 2016 SCCS conclusion Although the Margin of Safety (MoS) calculated on the basis of oral exposure to daidzein comes out at marginally below 100 (96), it is much higher than 100 (385) when exposure via subcutaneous route is taken into account. Taking into view that the value of 25% used for oral bioavailability is very conservative, and that the subcu","page":72,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_032"} |
| SCCS_vision_codex | NOAEL | =119 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 119: Genistein doses and study design | Most sensitive endpoints and generation | NOEL/ NOAEL | LOEL/ LOAEL | BMD10 a | BMDL1 0 | BMD 1 SD | BMDL1 SD | Reference","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_040"} |
| SCCS_vision_codex | NOAEL | =119 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 119: Genistein doses and study design | Most sensitive endpoints and generation | NOEL/ NOAEL | LOEL/ LOAEL | BMD10 a | BMDL1 0 | BMD 1 SD | BMDL1 SD | Reference","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_040"} |
| SCCS_vision_codex | NOAEL | =119 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 119: Genistein doses and study design | Most sensitive endpoints and generation | NOEL/ NOAEL | LOEL/ LOAEL | BMD10 a | BMDL1 0 | BMD 1 SD | BMDL1 SD | Reference","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_040"} |
| SCCS_vision_codex | NOAEL | =119 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 119: Genistein doses and study design | Most sensitive endpoints and generation | NOEL/ NOAEL | LOEL/ LOAEL | BMD10 a | BMDL1 0 | BMD 1 SD | BMDL1 SD | Reference","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_040"} |
| SCCS_vision_codex | NOAEL | =1250 | ppm | - | oral | - | NOAEL study | {"dose":"Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy:","effect":"Unlabeled table on page 119: Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy: 34 | 83 | Delclos et al. (2001)","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_048"} |
| SCCS_vision_codex | NOAEL | =1250 | ppm | - | oral | - | NOAEL study | {"dose":"Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy:","effect":"Unlabeled table on page 119: Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy: 34 | 83 | Delclos et al. (2001)","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_048"} |
| SCCS_vision_codex | NOAEL | =1250 | ppm | - | oral | - | NOAEL study | {"dose":"Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy:","effect":"Unlabeled table on page 119: Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy: 34 | 83 | Delclos et al. (2001)","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_048"} |
| SCCS_vision_codex | NOAEL | =1250 | ppm | - | oral | - | NOAEL study | {"dose":"Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy:","effect":"Unlabeled table on page 119: Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy: 34 | 83 | Delclos et al. (2001)","page":119,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_048"} |
| SCCS_vision_codex | NOAEL | =2000 | mg/kg bw/day | rat | - | developmental | developmental toxicity | {"dose":"has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","effect":"SCCS-rejected applicant NOAEL: has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to daidzein only but to a new Equol-rich soy product (SE5-OH) which contains approximately 0.65% Equol, 0.024% daidzein, 0.022% genistein, and 0.30% Glycitein. This study cannot be used for MoS calculation because the SCCS considers that only the studies performed with pure daidzein are relevant for safety assessmen","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_009"} |
| SCCS_vision_codex | NOAEL | =2000 | mg/kg bw/day | rat | - | developmental | developmental toxicity | {"dose":"has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","effect":"SCCS-rejected applicant NOAEL: has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to daidzein only but to a new Equol-rich soy product (SE5-OH) which contains approximately 0.65% Equol, 0.024% daidzein, 0.022% genistein, and 0.30% Glycitein. This study cannot be used for MoS calculation because the SCCS considers that only the studies performed with pure daidzein are relevant for safety assessmen","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_009"} |
| SCCS_vision_codex | NOAEL | =2000 | mg/kg bw/day | rat | - | developmental | developmental toxicity | {"dose":"has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","effect":"SCCS-rejected applicant NOAEL: has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to daidzein only but to a new Equol-rich soy product (SE5-OH) which contains approximately 0.65% Equol, 0.024% daidzein, 0.022% genistein, and 0.30% Glycitein. This study cannot be used for MoS calculation because the SCCS considers that only the studies performed with pure daidzein are relevant for safety assessmen","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_009"} |
| SCCS_vision_codex | NOAEL | =2000 | mg/kg bw/day | rat | - | developmental | developmental toxicity | {"dose":"has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","effect":"SCCS-rejected applicant NOAEL: has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to daidzein only but to a new Equol-rich soy product (SE5-OH) which contains approximately 0.65% Equol, 0.024% daidzein, 0.022% genistein, and 0.30% Glycitein. This study cannot be used for MoS calculation because the SCCS considers that only the studies performed with pure daidzein are relevant for safety assessmen","page":37,"pdf":"sccs_o_263.pdf","row_type":"noael_study","study_id":"sccs_o_263_noael_009"} |
ToxValDB_HESS 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_HESS | NOEL | =50 | mg/kg bw/day | Rat | oral | - | subchronic | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/60da0deee4b0a676289de876; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.nite.go.jp/en/chem/qsar/hess_update-e.html; TOXICOLOGICAL_EFFECT=Body Weight Changes: decrease|Food Consumption: decrease|Hematology: RBC decrease, Ret increase, , Hgb decrease|Blood Chemistry: gamma-GTP increase, , Cho decrease, TP decrease; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|clinical chemistry|food and/or water consumption|hematology; STUDY_GROUP=HESS:15638543:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_9e202fd70154e0290403826d4288f81e |
ToxValDB_Uterotrophic_Hershberger_DB 30 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =0.00027024 | mg | Mouse | injection | acute; 0.17 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713695:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_f55d0467f3acb308ff4365187f5a20d0 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =0.0025 | mg/kg bw/day | Rat | injection | short-term; 7 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713409_15713524:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_4915b738822e0727db98cc58d8337f4f |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =0.02 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_256d6d030adf5a9b87e8ec84558badb0 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =0.4 | mg | Rat | injection | acute; 1 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713778:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_9ca13a9196f3327673dfbf3881796c07 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =0.5 | mg/day | Mouse | injection | short-term; 10 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713895:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_073273dc259ed7ffbe71f5c989703717 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =0.62 | mg | Rat | injection | acute; 1 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713287:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_37e7e9ce594e3c95fd0667a19c7a5c6d |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =0.8 | mg | Mouse | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713780:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_1239d8a561d7b6d33ae7e952c455c5b3 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =1 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_176e56d5a0a844a1b53b5834316d960d |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =1.25 | mg/day | Mouse | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713350:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_300630ae3524427436e582b157500e1d |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =2 | mg/day | Mouse | injection | short-term; 4 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713355:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_3917739ddbe32455025e1a7f8bf31f9b |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =2.5 | mg/day | Mouse | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713359_15713370:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_7d5d927360d5a67af2817106a4beab58 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =2.5 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_edfe44b08b825db0e1203660df7d145f |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =3 | mg/day | Mouse | injection | short-term; 14 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713357_15713363_15713367:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_1b7e3c3a234e21a8b30c102e7f0db0d0 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =5 | mg/day | Mouse | injection | short-term; 14 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713357_15713363_15713367:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_60d0338333c1da444aa3fae919abd985 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =5 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_55cf8f72e8374d4388adf631831c6cea |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =5.77 | mg | Mouse | oral | short-term; 6 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713298:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_35988c9512ed126434fd60506256f120 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =6 | mg/day | Mouse | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713359_15713370:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_9e7fe150dc9d27959542091055f0b297 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =10 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0 |::| 1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_d64cb6a75fdff5e68796834139379592 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =15 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ebcb7f51b41c0259e650f2ae77b7b969 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =20 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_d1467dcc9c5353d8aeaac79ee8fa90c0 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =25 | mg/kg bw/day | Mouse | injection | short-term; 28 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713548:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_820d53c8b3928dafa3623aca0d4b8f6c |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =30 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_75444e7cb6f88068ef30790f3428ee80 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =35 | mg/kg bw/day | Rat | injection | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0 |::| 1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713459_15713480_15713494_15713509_15713523_15713532_15713549_15713555_15713983:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_c474e5d636776b16da5c9dfca245ed8f |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =50 | mg/kg bw/day | Rat | oral | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713265_15713463_15713534_15713575_15713579_15713610:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_58a73199077536859d98d60cb0a4e254 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =60 | mg/kg bw/day | Rat | oral | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713265_15713463_15713534_15713575_15713579_15713610:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_fa8adb46bc9e0f9596b88db72325294f |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =100 | mg/kg bw/day | Rat | oral | short-term; 3 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB_dup_-_15713265_15713463_15713534_15713575_15713579_15713610:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0acad158d3a7ef6804a97253a36db2b8 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =125 | mg/kg bw/day | Rat | oral | short-term; 30 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713621:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_8c56c0722e211ab176726c5dfd83f391 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =200 | mg/kg bw/day | Mouse | oral | short-term; 7 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=1; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713650:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_888c23ee1d3078e2c4796f2a46bd12c2 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =250 | mg/kg bw/day | Rat | injection | short-term; 14 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713655:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_c1f2f923d75962cc4ea142c6af282526 |
| ToxValDB_Uterotrophic_Hershberger_DB | LEL | =375 | mg/kg bw/day | Rat | oral | short-term; 5 days | uterotrophic | LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713902:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_601656b99a9880b1f69baf3a68868f9d |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 50 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 4 | mg/kg bw/day | - | oral | 2 weeks | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=4; DOSE=Testis weights were unaffected by either dose of genistein.; EFFECT=ornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein Lamartiniere et al., 2002 Guidelines/Guidances: / Test item: daidzein Purity: 98.5% (HPLC) Impurity: 1.5 % Methanol Vehicle: feed (phytoestrogen-free AIN-76A diet) Route of exposure: oral (feed) Duration of exposure: 2 weeks before breedin; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Testis weights were unaffected by either dose of genistein.","duration":"2 weeks","effect":"ornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein Lamartiniere et al., 2002 Guidelines/Guidances: / Test item: daidzein Purity: 98.5% (HPLC) Impurity: 1.5 % Methanol Vehicle: feed (phytoestrogen-free AIN-76A diet) Route of exposure: oral (feed) Duration of exposure: 2 weeks before breedin","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"4","page":32,"route":"oral","species":"","study_id":"sccs_o_263_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 4 | mg/kg bw/day | rat | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=4; DOSE=SAFETY EVALUATION (including calculation of the MoS) Genistein From the NTP study detailed in section 3.3.5.1, the SCCS identified a LOAEL of 100 ppm (equivalent to 7.4 mg/kg bw/day for male and 10.2 mg/kg bw/day for female rat) as the toxicological point of departure (PoD).; LOAEL_VALUE=7.4 mg/kg bw/day; EFFECT=information, the SCCS considers that the toxicological point of departure (PoD) selected for the safety assessment of genistein (see section 3.4) also adequately covers its endocrine-related effects. 3.4. SAFETY EVALUATION (including calculation of the MoS) Genistein From the NTP study detailed in section 3.3.5.1, the SCCS identified a LOAEL of 100 ppm (equivalent to 7.4 mg/kg bw/day for male and 10.2 mg/kg bw/day for female rat) as the toxicological point of departure (PoD). Furthermore, the SCCS identified a NOAEL of 4 mg/kg bw/day as the toxicological PoD for the subcutaneous route from the study by Lewis (2003) that is also detailed in section 3.3.5.1.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"SAFETY EVALUATION (including calculation of the MoS) Genistein From the NTP study detailed in section 3.3.5.1, the SCCS identified a LOAEL of 100 ppm (equivalent to 7.4 mg/kg bw/day for male and 10.2 mg/kg bw/day for female rat) as the toxicological point of departure (PoD).","duration":"","effect":"information, the SCCS considers that the toxicological point of departure (PoD) selected for the safety assessment of genistein (see section 3.4) also adequately covers its endocrine-related effects. 3.4. SAFETY EVALUATION (including calculation of the MoS) Genistein From the NTP study detailed in section 3.3.5.1, the SCCS identified a LOAEL of 100 ppm (equivalent to 7.4 mg/kg bw/day for male and 10.2 mg/kg bw/day for female rat) as the toxicological point of departure (PoD). Furthermore, the SCCS identified a NOAEL of 4 mg/kg bw/day as the toxicological PoD for the subcutaneous route from the study by Lewis (2003) that is also detailed in section 3.3.5.1.","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"7.4 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"4","page":69,"route":"","species":"rat","study_id":"sccs_o_263_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =5 | - | rat | - | 30 days | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=LOEL = 5mk/kg sc; EFFECT=Unlabeled table on page 153: Romero et al., 2019 | Daidzein | Wistar rats | female | ovariecto mized | sc | 5 mg/k g | 30 days | estradiol | In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increased uterine and vaginal epithelium in proestrus and diestrus periods, increased uterine and vaginal relative weights during diestrus, and decreased serum progesterone during proestrus All these effects were similar to those of DAI but lower than E2- induced effects. In OVX females, DAI decreased body weight, induced lordosis, | These results indicate that, in gonadally intact females, LEU (and DAI) can produce antiestrogenic effects in sexual behavior but estrogenic effects on uterine and vaginal weight and epithelia, without modifying serum levels of E2. In OVX females, in total absence of endogenous E2, LEU induced estrogenic effects on vaginal weight and epithelia, as | LOEL = 5mk/kg sc; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"","duration":"30 days","effect":"Unlabeled table on page 153: Romero et al., 2019 | Daidzein | Wistar rats | female | ovariecto mized | sc | 5 mg/k g | 30 days | estradiol | In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increased uterine and vaginal epithelium in proestrus and diestrus periods, increased uterine and vaginal relative weights during diestrus, and decreased serum progesterone during proestrus All these effects were similar to those of DAI but lower than E2- induced effects. In OVX females, DAI decreased body weight, induced lordosis, | These results indicate that, in gonadally intact females, LEU (and DAI) can produce antiestrogenic effects in sexual behavior but estrogenic effects on uterine and vaginal weight and epithelia, without modifying serum levels of E2. In OVX females, in total absence of endogenous E2, LEU induced estrogenic effects on vaginal weight and epithelia, as | LOEL = 5mk/kg sc","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"LOEL = 5mk/kg sc","page":153,"route":"","species":"rat","study_id":"sccs_o_263_noael_050"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 7.4 | mg/kg bw | human | oral | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=7.4; DOSE=Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...; LOAEL_VALUE=7.4 mg/kg bw; EFFECT=______________________ _______________________________________________________________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...","duration":"","effect":"______________________ _______________________________________________________________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed a","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"7.4 mg/kg bw","noael_unit":"mg/kg bw","noael_value":"7.4","page":70,"route":"oral","species":"human","study_id":"sccs_o_263_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 7.4 | mg/kg bw | human | oral | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=7.4; DOSE=Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...; LOAEL_VALUE=7.4 mg/kg bw; EFFECT=______ _______________________________________________________________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect le; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...","duration":"","effect":"______ _______________________________________________________________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect le","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"7.4 mg/kg bw","noael_unit":"mg/kg bw","noael_value":"7.4","page":70,"route":"oral","species":"human","study_id":"sccs_o_263_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 7.4 | mg/kg bw | human | oral | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=7.4; DOSE=Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...; LOAEL_VALUE=7.4 mg/kg bw; EFFECT=_____________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Marg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4...","duration":"","effect":"_____________________ 70 MoS calculation based on PoD by the oral route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 LOAEL 100 ppm (7.4 mg/kg bw) (mg/kg bw/d) 7.4 Adjusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Marg","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"7.4 mg/kg bw","noael_unit":"mg/kg bw","noael_value":"7.4","page":70,"route":"oral","species":"human","study_id":"sccs_o_263_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 15 | mg/kg bw | - | oral | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=15; DOSE=Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al.; EFFECT=Unlabeled table on page 119: Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al. (2004); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al.","duration":"","effect":"Unlabeled table on page 119: Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. | Uterine histomorphometry endpoints | 15 | Hughes et al. (2004)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw","noael_value":"15","page":119,"route":"oral","species":"","study_id":"sccs_o_263_noael_041"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=20; EFFECT=Unlabeled table on page 119: ↓Weight at vaginal opening, | 20 | 87 | 55 | 36 | 59 | 36; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 119: ↓Weight at vaginal opening, | 20 | 87 | 55 | 36 | 59 | 36","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"20","page":119,"route":"","species":"","study_id":"sccs_o_263_noael_043"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=20; EFFECT=Unlabeled table on page 119: ↑Uterus weight on PND 21 | 20 | 87 | 5 | 3 | 24 | 17; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 119: ↑Uterus weight on PND 21 | 20 | 87 | 5 | 3 | 24 | 17","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"20","page":119,"route":"","species":"","study_id":"sccs_o_263_noael_044"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=20; EFFECT=Unlabeled table on page 119: ↑Relative testis weight on PND 21 | 20 | 87 | 171 | 103 | 64 | 38; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 119: ↑Relative testis weight on PND 21 | 20 | 87 | 171 | 103 | 64 | 38","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"20","page":119,"route":"","species":"","study_id":"sccs_o_263_noael_045"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=20; EFFECT=Unlabeled table on page 119: ↑Relative testis weight on PND 56 | 20 | 87 | 180 | 81 | 118 | 54; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 119: ↑Relative testis weight on PND 56 | 20 | 87 | 180 | 81 | 118 | 54","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"20","page":119,"route":"","species":"","study_id":"sccs_o_263_noael_046"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=20; EFFECT=Unlabeled table on page 119: ↓Vental prostate weight | 20 | 87; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 119: ↓Vental prostate weight | 20 | 87","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"20","page":119,"route":"","species":"","study_id":"sccs_o_263_noael_047"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | % | human | oral | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=25; DOSE=djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route:; EFFECT=djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route:","duration":"","effect":"djusted NOAEL (LOAEL to NOAEL) (mg/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"25","page":70,"route":"oral","species":"human","study_id":"sccs_o_263_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | % | human | oral | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=25; DOSE=/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route:; EFFECT=/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the data fr; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route:","duration":"","effect":"/kg bw/d) 2.5 Bioavailability (%) 25 Adjusted NOAEL (mg/kg bw/d) 0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the data fr","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"25","page":70,"route":"oral","species":"human","study_id":"sccs_o_263_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 25 | % | human | oral | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=25; DOSE=Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg...; EFFECT=0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the data from subcutaneous route provides a more reliable indicator of safety,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg...","duration":"","effect":"0.617 Margin of Safety (NOAELadj/SED) 135 MoS calculation based on PoD by the subcutaneous route: Amount of product applied daily (g/day) 7.82 Typical body weight of human (kg) 60 Amount of product applied daily (mg/kg bw) 130 Concentration of genistein (%) 0.007 Amount of genistein applied daily (mg/kg bw) 0.0091 Absorption through the skin (%) 50 Systemic exposure dose (SED) (mg/kg bw/d) 0.0046 No observed adverse effect level (NOAEL mg/kg bw/d) 4.00 Bioavailability (%) 100 Margin of Safety (NOAEL/SED) 876 Because of the large uncertainties associated with oral absorption of genistein in humans, and rapid conjugation of the absorbed genistein aglycone, the SCCS considers that the use of data from subcutaneous studies in this case is also reliable and justified than the data from oral studies, for which 25% oral bioavailability is applied. The SCCS considers that the calculation of margin of safety (MoS) for genistein based on the data from subcutaneous route provides a more reliable indicator of safety,","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"25","page":70,"route":"oral","species":"human","study_id":"sccs_o_263_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =35 | mg/kg | rat | - | 30 days | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT== 35; DOSE=Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation NOAEL = 35 mg/kg sc Romero et al., 2019 Daidzein Wistar rats female ovariecto mized sc 5 mg/k g 30 days estradiol In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increa...; EFFECT=ine compartments as well as LAC and VEGF gene expression. Absence of hyperplastic changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remain unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation NOAEL = 35 mg/kg sc Romero et al., 2019 Daidzein Wistar rats female ovariecto mized sc 5 mg/k g 30 days estradiol In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increased uterine and vaginal epithelium in proestrus and diestrus periods, increased uterine and vaginal relative weights during diestrus, and decreased serum progesterone during proestrus All these effects were similar to those of DAI but lower than E2- induced effects. In OVX; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation NOAEL = 35 mg/kg sc Romero et al., 2019 Daidzein Wistar rats female ovariecto mized sc 5 mg/k g 30 days estradiol In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increa...","duration":"30 days","effect":"ine compartments as well as LAC and VEGF gene expression. Absence of hyperplastic changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remain unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation NOAEL = 35 mg/kg sc Romero et al., 2019 Daidzein Wistar rats female ovariecto mized sc 5 mg/k g 30 days estradiol In intact females, DAI disrupted the estrous cycle and female sexual behavior, decreased the number of follicles and corpora lutea, increased uterine and vaginal epithelium in proestrus and diestrus periods, increased uterine and vaginal relative weights during diestrus, and decreased serum progesterone during proestrus All these effects were similar to those of DAI but lower than E2- induced effects. In OVX","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"= 35","page":153,"route":"","species":"rat","study_id":"sccs_o_263_noael_039"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =35 | mg/kg | rat | - | 12 months | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT== 35; DOSE=Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. | Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation | NOAEL = 35 mg/kg sc; EFFECT=Unlabeled table on page 153: Jaric et al., 2016 PMID: 29217487 | Daidzein | Wistar rats | female | 12 months ovarian intact | sc | 35 mg/k g | 4 weeks | Genistein | DAI did not change the uterine wet weight and stereological features of the main uterine compartments as well as LAC and VEGF gene expression. Absence of hyperplastic changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remain unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. | Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation | NOAEL = 35 mg/kg sc; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. | Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation | NOAEL = 35 mg/kg sc","duration":"12 months","effect":"Unlabeled table on page 153: Jaric et al., 2016 PMID: 29217487 | Daidzein | Wistar rats | female | 12 months ovarian intact | sc | 35 mg/k g | 4 weeks | Genistein | DAI did not change the uterine wet weight and stereological features of the main uterine compartments as well as LAC and VEGF gene expression. Absence of hyperplastic changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remain unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. | Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation | NOAEL = 35 mg/kg sc","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"= 35","page":153,"route":"","species":"rat","study_id":"sccs_o_263_noael_049"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | mg/kg/day | - | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=40; DOSE=_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups.; EFFECT=_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein L; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups.","duration":"","effect":"_____________________________________________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein L","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"40","page":32,"route":"","species":"","study_id":"sccs_o_263_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | mg/kg/day | - | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=40; DOSE=___________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups.; EFFECT=___________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein Lamartin; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"___________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups.","duration":"","effect":"___________________________ 32 opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. From this study, the SCCS identified 4 mg/kg bw/day of genistein as the NOAEL for the subcutaneous route. There were no effects in females dosed with 4 mg/kg genistein. Testis weights (analyzed by litter, with adjustment for body weight) were significantly reduced by DES but were unaffected by either dose of genistein. 3.3.5.2 Daidzein Lamartin","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"40","page":32,"route":"","species":"","study_id":"sccs_o_263_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | mg/kg/day | rat | - | 12 weeks | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=40; DOSE=The time of vaginal opening was four days earlier in females in the high-dose group and in most developing female pups.; EFFECT=l values in mature females at 12 weeks of age. The time of vaginal opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. McClain et al. (2006) reported a feeding study with genistein in rats with 5, 50, and 500 mg/kg/day over 4, 13, and 52 weeks with an interim sacrifice after 26 weeks for histopathology. At 500 mg/kg/day there was an increase in uterus weight after 4 and 13 weeks of treatment. These changes are most probably within the range of physiologica; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"The time of vaginal opening was four days earlier in females in the high-dose group and in most developing female pups.","duration":"12 weeks","effect":"l values in mature females at 12 weeks of age. The time of vaginal opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. McClain et al. (2006) reported a feeding study with genistein in rats with 5, 50, and 500 mg/kg/day over 4, 13, and 52 weeks with an interim sacrifice after 26 weeks for histopathology. At 500 mg/kg/day there was an increase in uterus weight after 4 and 13 weeks of treatment. These changes are most probably within the range of physiologica","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"40","page":60,"route":"","species":"rat","study_id":"sccs_o_263_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 40 | mg/kg/day | rat | - | 52 weeks | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=40; DOSE=The time of vaginal opening was four days earlier in females in the high-dose group and in most developing female pups.; EFFECT=eeks of age. The time of vaginal opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. McClain et al. (2006) reported a feeding study with genistein in rats with 5, 50, and 500 mg/kg/day over 4, 13, and 52 weeks with an interim sacrifice after 26 weeks for histopathology. At 500 mg/kg/day there was an increase in uterus weight after 4 and 13 weeks of treatment. These changes are most probably within the range of physiological varia; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"The time of vaginal opening was four days earlier in females in the high-dose group and in most developing female pups.","duration":"52 weeks","effect":"eeks of age. The time of vaginal opening was four days earlier in females in the high-dose group and in most developing female pups. At 40 mg/kg bw for the animals smeared from the time of vaginal opening, 13/20 showed permanent estrus (persistent cornification) with 19/20 of the animals smeared from day 43 showing this pattern. The time of preputial separation in males was not affected by administration of genistein. Testis weights were unaffected by either dose of genistein. The no observed adverse effect level (NOAEL) of genistein was considered to be between 4 and 40 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. McClain et al. (2006) reported a feeding study with genistein in rats with 5, 50, and 500 mg/kg/day over 4, 13, and 52 weeks with an interim sacrifice after 26 weeks for histopathology. At 500 mg/kg/day there was an increase in uterus weight after 4 and 13 weeks of treatment. These changes are most probably within the range of physiological varia","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"40","page":60,"route":"","species":"rat","study_id":"sccs_o_263_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =100 | % | rat | oral | 90-day | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT== 100; DOSE=____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein ap...; EFFECT=____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 Low observed adverse effect level NOAEL mg/kg bw/d = 5 (90-day, sc, rat*) Bioavailability % = 100% Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety PODsys/SED = 385 * Retana Marquez, 2016 SCCS conclusion Although the Margin of Safety (MoS) calculated on the basis of oral exposure to daidzein comes out at marginally below 100 (96), it is much higher than 100 (385) when exposure via subcutaneous route is taken into account. Taking into view that the value of 25% used for oral bioavailability is very conservative, and that the subcu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein ap...","duration":"90-day","effect":"____________________________________________ _______________________________________________________________________ 72 Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 Low observed adverse effect level NOAEL mg/kg bw/d = 5 (90-day, sc, rat*) Bioavailability % = 100% Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety PODsys/SED = 385 * Retana Marquez, 2016 SCCS conclusion Although the Margin of Safety (MoS) calculated on the basis of oral exposure to daidzein comes out at marginally below 100 (96), it is much higher than 100 (385) when exposure via subcutaneous route is taken into account. Taking into view that the value of 25% used for oral bioavailability is very conservative, and that the subcu","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"= 100","page":72,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_032"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 100 | ppm | rat | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=100; DOSE=Pregnant Sprague-Dawley rats were fed diets containing 0, 20, or 100 ppm genistein [0, 20, or 87 mg/kg bw/day]. | ↑Anogenital distance | 20 | 87 | 54 | 34 | 54 | 34 | Casanova et al.; EFFECT=Unlabeled table on page 119: Pregnant Sprague-Dawley rats were fed diets containing 0, 20, or 100 ppm genistein [0, 20, or 87 mg/kg bw/day]. | ↑Anogenital distance | 20 | 87 | 54 | 34 | 54 | 34 | Casanova et al. (1999); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Pregnant Sprague-Dawley rats were fed diets containing 0, 20, or 100 ppm genistein [0, 20, or 87 mg/kg bw/day]. | ↑Anogenital distance | 20 | 87 | 54 | 34 | 54 | 34 | Casanova et al.","duration":"","effect":"Unlabeled table on page 119: Pregnant Sprague-Dawley rats were fed diets containing 0, 20, or 100 ppm genistein [0, 20, or 87 mg/kg bw/day]. | ↑Anogenital distance | 20 | 87 | 54 | 34 | 54 | 34 | Casanova et al. (1999)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"100","page":119,"route":"","species":"rat","study_id":"sccs_o_263_noael_042"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 119 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=unclear:Unlabeled table on page 119: Genistein doses and study design | Most sensitive endpoints and generation | NOEL/ NOAEL | LOEL/ LOAEL | BMD10 a | BMDL1 0 | BMD 1 SD | BMDL1 SD | Reference; EFFECT=Unlabeled table on page 119: Genistein doses and study design | Most sensitive endpoints and generation | NOEL/ NOAEL | LOEL/ LOAEL | BMD10 a | BMDL1 0 | BMD 1 SD | BMDL1 SD | Reference; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 119: Genistein doses and study design | Most sensitive endpoints and generation | NOEL/ NOAEL | LOEL/ LOAEL | BMD10 a | BMDL1 0 | BMD 1 SD | BMDL1 SD | Reference","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 119: Genistein doses and study design | Most sensitive endpoints and generation | NOEL/ NOAEL | LOEL/ LOAEL | BMD10 a | BMDL1 0 | BMD 1 SD | BMDL1 SD | Reference","page":119,"route":"","species":"","study_id":"sccs_o_263_noael_040"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1250 | ppm | - | oral | - | - | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=1250; DOSE=Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy:; EFFECT=Unlabeled table on page 119: Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy: 34 | 83 | Delclos et al. (2001); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy:","duration":"","effect":"Unlabeled table on page 119: Sprague-Dawley, 0, 5, 25, 100, 250, 625, and 1250 ppm through diet during pregnancy and lactation and until PND 50 | ↓Dams delivering litters; delayed eye opening | Pregnancy: 34 | 83 | Delclos et al. (2001)","endpoint":"","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"1250","page":119,"route":"oral","species":"","study_id":"sccs_o_263_noael_048"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | carcinogenicity | 16 | mg/kg bw/d | pig | oral | Chronic | carcinogenicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=16; DOSE=Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d.; EFFECT=inal version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 28 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, a variety of toxicologically relevant parameters have been investigated in the study, and adverse effects are observed at 400 mg/daidzein/kg diet and a NOAEL of 200 mg daidzein/kg diet. Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d. 3.3.4.2.3 Chronic (> 12 months) toxicity Under the conditions of a 2-year feed study with continuous exposure to the test compound from conception through termination (F1C), there was no evidence of carcinogenic activit; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d.","duration":"Chronic","effect":"inal version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 28 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, a variety of toxicologically relevant parameters have been investigated in the study, and adverse effects are observed at 400 mg/daidzein/kg diet and a NOAEL of 200 mg daidzein/kg diet. Based on the weight range of weaned, growing pigs, a body weight range between 12 and 50 kg and food consumption between 4 and 8 kg (https://agritech.tnau.ac.in/animal_husbandry/ani_pig_feeding%20mgt.html) can be assumed, resulting in an intake level of 16 mg/kg bw/d. 3.3.4.2.3 Chronic (> 12 months) toxicity Under the conditions of a 2-year feed study with continuous exposure to the test compound from conception through termination (F1C), there was no evidence of carcinogenic activit","endpoint":"carcinogenicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"16","page":28,"route":"oral","species":"pig","study_id":"sccs_o_263_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 2000 | mg/kg bw/day | rat | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=2000; DOSE=has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.; EFFECT=SCCS-rejected applicant NOAEL: has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to daidzein only but to a new Equol-rich soy product (SE5-OH) which contains approximately 0.65% Equol, 0.024% daidzein, 0.022% genistein, and 0.30% Glycitein. This study cannot be used for MoS calculation because the SCCS considers that only the studies performed with pure daidzein are relevant for safety assessmen; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","duration":"developmental","effect":"SCCS-rejected applicant NOAEL: has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to daidzein only but to a new Equol-rich soy product (SE5-OH) which contains approximately 0.65% Equol, 0.024% daidzein, 0.022% genistein, and 0.30% Glycitein. This study cannot be used for MoS calculation because the SCCS considers that only the studies performed with pure daidzein are relevant for safety assessmen","endpoint":"developmental toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2000","page":37,"route":"","species":"rat","study_id":"sccs_o_263_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 100 | mg/kg bw/d | pig | oral | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=100; DOSE=However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein.; EFFECT=SCCS/1641/22 Final version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 27 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein. 3.3.4.2.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline/Guidance: / Species/Strain: crossbred [(Large White × Landrace) × Duroc] weaned pigs Group size: 12/sex/dose Test item: daidzein Purity: 98% Control: NRC (1998) standard commercial feed without any soy source Route of exposure: Oral, diet Duration: 70 days Doses: 0, 40, 200 and 400 mg daidzein/kg diet Study period: not stated, publication submitted in 2013 GLP:; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein.","duration":"28-day","effect":"SCCS/1641/22 Final version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 27 SCCS comment This study is described from open literature and the original study report is not available to the SCCS. However, it indicates that the highest dose of 100 mg/kg bw/d can be considered as NOAEL after 28-day repeated oral administration of daidzein. 3.3.4.2.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline/Guidance: / Species/Strain: crossbred [(Large White × Landrace) × Duroc] weaned pigs Group size: 12/sex/dose Test item: daidzein Purity: 98% Control: NRC (1998) standard commercial feed without any soy source Route of exposure: Oral, diet Duration: 70 days Doses: 0, 40, 200 and 400 mg daidzein/kg diet Study period: not stated, publication submitted in 2013 GLP:","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"100","page":27,"route":"oral","species":"pig","study_id":"sccs_o_263_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 100 | mg/kg bw/d | rat | oral | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=100; DOSE=Repeated dose toxicity For genistein, a number of repeated dose toxicological studies are available.; EFFECT=s that the acute toxicity of both genistein and daidzein is low. Repeated dose toxicity For genistein, a number of repeated dose toxicological studies are available. These have been described in sections 3.3.4, section 3.3.10.1 (under level 5), and in the Annex-A Tables. For daidzein, one 28-day oral study in rats and one 700day oral study in pigs were described from the open literature but the original study reports were not available to the SCCS. These studies indicate that 100 mg/kg bw/d can be considered as NOAEL in rats after 28-day repeated oral administration of daidzein and 200 mg/kg bw/d in pigs after 70 days exposure to daidzein/kg diet.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Repeated dose toxicity For genistein, a number of repeated dose toxicological studies are available.","duration":"28-day","effect":"s that the acute toxicity of both genistein and daidzein is low. Repeated dose toxicity For genistein, a number of repeated dose toxicological studies are available. These have been described in sections 3.3.4, section 3.3.10.1 (under level 5), and in the Annex-A Tables. For daidzein, one 28-day oral study in rats and one 700day oral study in pigs were described from the open literature but the original study reports were not available to the SCCS. These studies indicate that 100 mg/kg bw/d can be considered as NOAEL in rats after 28-day repeated oral administration of daidzein and 200 mg/kg bw/d in pigs after 70 days exposure to daidzein/kg diet.","endpoint":"repeated dose toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"100","page":74,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_033"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 0.02 | % | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=0.02; DOSE=(2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL.; EFFECT=alsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"(2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL.","duration":"developmental","effect":"alsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"0.02","page":71,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 0.3 | % | rat | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=0.3; DOSE=In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.; EFFECT=nt, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to da; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein.","duration":"developmental","effect":"nt, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH has been administered, which is an equol-rich soy product prepared by bacterial fermentation and contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein and 0.3 % Glycitein. In that study, the NOAEL for SE5-OH determined for both male and female rats was 1000 mg/kg bw/day (6.5 mg Equol/kg/day), based on a reduction of body weight, implantations, and live births in the F1 and F2 animals at the 1000 mg/kg bw/day dose level. For the developmental part of that study, the study authors concluded that the NOAEL for developmental effects of SE5-OH is 2000 mg/kg bw/day, based on the lack of significant embryo-to-fetal stage effect. SCCS comment In the study from Matulka et al. (2009), the rats were not exposed to da","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"%","noael_value":"0.3","page":37,"route":"","species":"rat","study_id":"sccs_o_263_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | mg/kg bw/d | human | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL.; EFFECT=t risks for human health. SCCS comment This study is described from the open literature and the original study report is not available to the SCCS. It is not a guideline study and not all parameters usually investigated in guideline studies were addressed. Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. With this statement SCCS concurs with the Nordic Council report of Ministers (2020) and with the NTP-CERHR (2010) as both consider thtn even if the study by Talsness et al. (2015) may be potentially relevant, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL.","duration":"","effect":"t risks for human health. SCCS comment This study is described from the open literature and the original study report is not available to the SCCS. It is not a guideline study and not all parameters usually investigated in guideline studies were addressed. Based on the effects described (reduction in cell height of the ovarian surface epithelium, increased rate of follicular atresia and greater prevalence of animals with a longer vaginal estrus), the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. With this statement SCCS concurs with the Nordic Council report of Ministers (2020) and with the NTP-CERHR (2010) as both consider thtn even if the study by Talsness et al. (2015) may be potentially relevant, due to limitations, it is not sufficiently robust to conclude that daidzein has reproductive effects in laboratory animals. In addition to these studies, the submission provided information from a reproductive toxicity study available in the public literature (Matulka et al., 2009). In that study, SE5- OH","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"5","page":37,"route":"","species":"human","study_id":"sccs_o_263_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | mg/kg bw/d | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=(2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility.; EFFECT=ble. Based on the observed effects in the most comprehensive study of Lamartinière et al. (2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility. Other studies have investigated more specific effects of daidzein that could have impact on the fertility or development. The study from Talsness et al. (2015) focused on the changes in the ovaries of female rats and based on the effects reported by the authors, the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. However, the biological consequences of these effects in terms of adversity are not known. As daidzein has also been associated with an estrogenic mode of action, the endocrine potential that may lead to adverse effects needs to be investigated before conclusions can be drawn about the reprotoxicity of this compound (see section 3.3.10) 3.3.6 Mutagenicity / genotoxicity As part of the safety assessment, the SCCS carefully examined all the in vitro and in vivo studies from the published literature until November; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"(2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility.","duration":"","effect":"ble. Based on the observed effects in the most comprehensive study of Lamartinière et al. (2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility. Other studies have investigated more specific effects of daidzein that could have impact on the fertility or development. The study from Talsness et al. (2015) focused on the changes in the ovaries of female rats and based on the effects reported by the authors, the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. However, the biological consequences of these effects in terms of adversity are not known. As daidzein has also been associated with an estrogenic mode of action, the endocrine potential that may lead to adverse effects needs to be investigated before conclusions can be drawn about the reprotoxicity of this compound (see section 3.3.10) 3.3.6 Mutagenicity / genotoxicity As part of the safety assessment, the SCCS carefully examined all the in vitro and in vivo studies from the published literature until November","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"5","page":38,"route":"","species":"rat","study_id":"sccs_o_263_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | mg/kg | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for th...; EFFECT=oute. Moreover, a significant skin penetration of daidzein would be considered because the SCCS considered appropriate to use the default value of 50% skin penetration (the submitter had proposed 100%). Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, derived from Talsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for th...","duration":"","effect":"oute. Moreover, a significant skin penetration of daidzein would be considered because the SCCS considered appropriate to use the default value of 50% skin penetration (the submitter had proposed 100%). Two PoDs are derived from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, derived from Talsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"5","page":71,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | mg/kg | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=d from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, deriv...; EFFECT=d from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, derived from Talsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied dail; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"d from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, deriv...","duration":"","effect":"d from the most sensitive endpoint reported in relevant studies: - A LOEL of 5 mg/kg for the subcutaneous route, derived from Retana–Marquez et al (2016); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. - A LOEL of 5 mg/kg for the oral route, derived from Talsness et al. (2015); as the effects reported were not directly associated with the reduction of fertility performances in rats, 5 mg/kg could be considered as a NOAEL. 1. MoS calculation based on the oral POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Talsness et al (2015) is considered as the POD for the calculation of the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied dail","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"5","page":71,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_027"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | mg/kg | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observe...; EFFECT=the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety adjusted PODsys/SED = 96 * Talsness et al., 2015 2. MoS calculation based on the subcutaneous POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Retana–Marquez et al (2016) is considered as the POD for the calculation of the MoS. As the effects reported were not directly associated to reduce fertility performances in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observe...","duration":"developmental","effect":"the Mos. As the effects reported were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety adjusted PODsys/SED = 96 * Talsness et al., 2015 2. MoS calculation based on the subcutaneous POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Retana–Marquez et al (2016) is considered as the POD for the calculation of the MoS. As the effects reported were not directly associated to reduce fertility performances in","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"5","page":71,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_029"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | mg/kg | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observe...; EFFECT=were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety adjusted PODsys/SED = 96 * Talsness et al., 2015 2. MoS calculation based on the subcutaneous POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Retana–Marquez et al (2016) is considered as the POD for the calculation of the MoS. As the effects reported were not directly associated to reduce fertility performances in male r; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observe...","duration":"developmental","effect":"were not directly associated to reduce fertility performances in the female rats, this LOEL could be considered as a NOAEL. Leave-on products with 0.02% Daidzein Amount of product applied daily: g/day = 7.82 Typical body weight of human: kg = 60 Amount of product applied daily: mg/kg bw = 130 Concentration of Daidzein: % = 0.02 Amount of Daidzein applied daily mg/kg bw = 0.026 Absorption through the skin % = 50 Systemic exposure dose (SED) mg/kg bw = 0.013 No Observed Adverse Effect Level NOAEL mg/kg bw/d = 5 (developmental study*, oral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety adjusted PODsys/SED = 96 * Talsness et al., 2015 2. MoS calculation based on the subcutaneous POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Retana–Marquez et al (2016) is considered as the POD for the calculation of the MoS. As the effects reported were not directly associated to reduce fertility performances in male r","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"5","page":71,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_030"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | mg/kg | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=ral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety adjusted PODsys/SED = 96 * Talsness et al., 2015 2.; EFFECT=ral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety adjusted PODsys/SED = 96 * Talsness et al., 2015 2. MoS calculation based on the subcutaneous POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Retana–Marquez et al (2016) is considered as the POD for the calculation of the MoS. As the effects reported were not directly associated to reduce fertility performances in male rats, this LOEL could be considered as a NOAEL.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"ral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety adjusted PODsys/SED = 96 * Talsness et al., 2015 2.","duration":"","effect":"ral, rat) Bioavailability oral route % = 25 Systemic POD PODsys mg/kg bw/d = 5 Margin of Safety adjusted PODsys/SED = 96 * Talsness et al., 2015 2. MoS calculation based on the subcutaneous POD Based on the analysis of the studies described above, the LOEL of 5 mg/kg derived from Retana–Marquez et al (2016) is considered as the POD for the calculation of the MoS. As the effects reported were not directly associated to reduce fertility performances in male rats, this LOEL could be considered as a NOAEL.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"5","page":71,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_031"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | mg/kg bw/d | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=(2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility.; EFFECT=able. Based on the observed effects in the most comprehensive study of Lamartinière et al. (2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility. Other studies have investigated more specific effects of daidzein that could have impact on the fertility or development. The study from Talsness et al., 2015 focused on the changes in the ovaries of female rats and based on the effects reported by the authors, the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. However, the biological consequences of these effects in terms of adversity are not known. As daidzein has also been associated with an estrogenic mode of action, endocrine potential that may lead to adverse effects needs to be investigated before conclusions can be drawn about the reprotoxicity of this compound (see section 3.3.10) Mutagenicity / genotoxicity Genistein Based on the available studies, genistein shows no evidence for mutagenicity in the bacterial gene mutation test (Ames tests). In contrast, in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"(2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility.","duration":"","effect":"able. Based on the observed effects in the most comprehensive study of Lamartinière et al. (2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility. Other studies have investigated more specific effects of daidzein that could have impact on the fertility or development. The study from Talsness et al., 2015 focused on the changes in the ovaries of female rats and based on the effects reported by the authors, the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. However, the biological consequences of these effects in terms of adversity are not known. As daidzein has also been associated with an estrogenic mode of action, endocrine potential that may lead to adverse effects needs to be investigated before conclusions can be drawn about the reprotoxicity of this compound (see section 3.3.10) Mutagenicity / genotoxicity Genistein Based on the available studies, genistein shows no evidence for mutagenicity in the bacterial gene mutation test (Ames tests). In contrast, in","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"5","page":75,"route":"","species":"rat","study_id":"sccs_o_263_noael_037"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 5 | ppm | rat | oral | Developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=5; DOSE=NTP TR 539 Multigenerational Reproductive study in rats - (Table 67 on Developmental Toxicity Studies in Orally- Exposed Rats from Rozman et al., 2006) Effect levels, mg/kg bw/day Genistein doses and study design Most sensitive endpoints and generation NOEL/ NOAEL LOEL/ LOAEL BMD10 a BMDL1 0 BMD 1 SD BMDL1 SD Reference Sprague-Dawley dams were f...; EFFECT=_____________________________________________________________________________________________________________ 119 Table A9: NTP TR 539 Multigenerational Reproductive study in rats - (Table 67 on Developmental Toxicity Studies in Orally- Exposed Rats from Rozman et al., 2006) Effect levels, mg/kg bw/day Genistein doses and study design Most sensitive endpoints and generation NOEL/ NOAEL LOEL/ LOAEL BMD10 a BMDL1 0 BMD 1 SD BMDL1 SD Reference Sprague-Dawley dams were fed diet containing 0 or 5 ppm genistein from GD 17 throughout the lactation period up to PND 70 in offspring. [Exposure in offspring estimated at ~0.68 mg/kg bw/day over the lifetime.] Changes in ovarian histology at PND 21 and 70 0.68b Awoniyi et al. (1998) Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. Uterine histomorphometry endpoints 15 Hughes et al. (2004) Pregnant Sprague-Dawley rats were fed diets; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"NTP TR 539 Multigenerational Reproductive study in rats - (Table 67 on Developmental Toxicity Studies in Orally- Exposed Rats from Rozman et al., 2006) Effect levels, mg/kg bw/day Genistein doses and study design Most sensitive endpoints and generation NOEL/ NOAEL LOEL/ LOAEL BMD10 a BMDL1 0 BMD 1 SD BMDL1 SD Reference Sprague-Dawley dams were f...","duration":"Developmental","effect":"_____________________________________________________________________________________________________________ 119 Table A9: NTP TR 539 Multigenerational Reproductive study in rats - (Table 67 on Developmental Toxicity Studies in Orally- Exposed Rats from Rozman et al., 2006) Effect levels, mg/kg bw/day Genistein doses and study design Most sensitive endpoints and generation NOEL/ NOAEL LOEL/ LOAEL BMD10 a BMDL1 0 BMD 1 SD BMDL1 SD Reference Sprague-Dawley dams were fed diet containing 0 or 5 ppm genistein from GD 17 throughout the lactation period up to PND 70 in offspring. [Exposure in offspring estimated at ~0.68 mg/kg bw/day over the lifetime.] Changes in ovarian histology at PND 21 and 70 0.68b Awoniyi et al. (1998) Long-Evans, 0 or 15 mg/kg bw by gavage on GD 14 to PND 21. Uterine histomorphometry endpoints 15 Hughes et al. (2004) Pregnant Sprague-Dawley rats were fed diets","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"ppm","noael_value":"5","page":119,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_038"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 19 | mg/kg bw/d | rat | oral | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=19; DOSE=Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL.; LOAEL_VALUE=19 mg/kg bw/d; EFFECT=________________________________________________________________ _______________________________________________________________________ 34 Otherwise, none of the daidzein doses had a significant effect on the weights and histomorphology of the female reproductive tract. SCCS comment This study is described in the open literature and the original study report is not available to the SCCS. Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL. Talsness et al., 2015 Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP Test item: daidzein (DZ) Purity: / Vehicle: 2% Corn starch Positive control: 17α-Ethinyl estradiol (EE) Purity / Vehicle: Peanut Oil Route of exposure: Oral - gavage Duration of exposure: GD 6 –GD 21 Doses: DZ: 0, 5 and 60 mg/kg bw/d; EE: 0.0002 mg/kg bw/d Experimental animals: Species: Rats Strain: Sprague Dawley Sex: Gravid female Animal numbers: 6 groups of 8-10 females (; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL.","duration":"","effect":"________________________________________________________________ _______________________________________________________________________ 34 Otherwise, none of the daidzein doses had a significant effect on the weights and histomorphology of the female reproductive tract. SCCS comment This study is described in the open literature and the original study report is not available to the SCCS. Based on the effects described, the SCCS considers the highest dose of 66 mg/kg bw/d as the LOAEL and 19 mg/kg bw/d as the NOAEL. Talsness et al., 2015 Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP Test item: daidzein (DZ) Purity: / Vehicle: 2% Corn starch Positive control: 17α-Ethinyl estradiol (EE) Purity / Vehicle: Peanut Oil Route of exposure: Oral - gavage Duration of exposure: GD 6 –GD 21 Doses: DZ: 0, 5 and 60 mg/kg bw/d; EE: 0.0002 mg/kg bw/d Experimental animals: Species: Rats Strain: Sprague Dawley Sex: Gravid female Animal numbers: 6 groups of 8-10 females (","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"19 mg/kg bw/d","noael_unit":"mg/kg bw/d","noael_value":"19","page":34,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 19 | mg/kg bw/d | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=19; DOSE=(2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility.; EFFECT=SCCS/1641/22 Final version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 38 Daidzein Only studies published in the literature were used by SCCS, but the original study reports were not available. Based on the observed effects in the most comprehensive study of Lamartinière et al. (2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility. Other studies have investigated more specific effects of daidzein that could have impact on the fertility or development. The study from Talsness et al. (2015) focused on the changes in the ovaries of female rats and based on the effects reported by the authors, the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. However, the biological consequences of these effects in terms of adversity are not known. As daidzein has also been associated with; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"(2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility.","duration":"","effect":"SCCS/1641/22 Final version Corrigendum October 2022 Opinion on genistein and daidzein ________________________________________________________________________________________ _______________________________________________________________________ 38 Daidzein Only studies published in the literature were used by SCCS, but the original study reports were not available. Based on the observed effects in the most comprehensive study of Lamartinière et al. (2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility. Other studies have investigated more specific effects of daidzein that could have impact on the fertility or development. The study from Talsness et al. (2015) focused on the changes in the ovaries of female rats and based on the effects reported by the authors, the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. However, the biological consequences of these effects in terms of adversity are not known. As daidzein has also been associated with","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"19","page":38,"route":"","species":"rat","study_id":"sccs_o_263_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 19 | mg/kg bw/d | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=19; DOSE=eport used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al.; LOAEL_VALUE=20 mg/kg bw; EFFECT=eport used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) for genistein in the current assessment. Daidzein Only studies published in the literature were used by SCCS, but the original study reports were not available. Based on the observed effects in the most comprehensive study of Lamartinière et al. (2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility. Other studies have investigated more specific effects of daidzein that could have impact on the fertility or development. The study from Talsness et al., 2015 focused on the changes in the ovaries of female rats and based on the effects reported by the authors, the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. However, the biological consequences of these effects in terms of adversity are not known. As daidzein has also been associated with; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"eport used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al.","duration":"","effect":"eport used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) for genistein in the current assessment. Daidzein Only studies published in the literature were used by SCCS, but the original study reports were not available. Based on the observed effects in the most comprehensive study of Lamartinière et al. (2002), the SCCS considers 19 mg/kg bw/d as a NOAEL for the effects on reproduction and fertility. Other studies have investigated more specific effects of daidzein that could have impact on the fertility or development. The study from Talsness et al., 2015 focused on the changes in the ovaries of female rats and based on the effects reported by the authors, the SCCS considers 60 mg/kg bw/d as a LO(A)EL and 5 mg/kg bw/d as a NO(A)EL. However, the biological consequences of these effects in terms of adversity are not known. As daidzein has also been associated with","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"20 mg/kg bw","noael_unit":"mg/kg bw/d","noael_value":"19","page":75,"route":"","species":"rat","study_id":"sccs_o_263_noael_036"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 35 | mg/kg | rat | - | 3 months | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=35; DOSE=SCCS comment In this study, 35 mg/kg could be considered as a NOAEL.; EFFECT=changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remained unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. In conclusion, compared to GEN, DAI did not promote events associated with the endometrial cell proliferation. SCCS comment In this study, 35 mg/kg could be considered as a NOAEL. In the study from Sergio et al. (2019), the authors aimed to investigate different female reproductive variables of leucaena and daidzein in ovariectomized or ovary intact rats. Daidzein was administered subcutaneously to ovariectomized or ovary intact Wistar rats (3 months old) at the dose of 5 mg/kg during 30 days. Estradiol was used as a positive control. In intact females, daidzein disrupted the estrous cycle and female sexual behaviour, decreased the number of follicles and corpora lutea, increased uterine; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"SCCS comment In this study, 35 mg/kg could be considered as a NOAEL.","duration":"3 months","effect":"changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remained unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. In conclusion, compared to GEN, DAI did not promote events associated with the endometrial cell proliferation. SCCS comment In this study, 35 mg/kg could be considered as a NOAEL. In the study from Sergio et al. (2019), the authors aimed to investigate different female reproductive variables of leucaena and daidzein in ovariectomized or ovary intact rats. Daidzein was administered subcutaneously to ovariectomized or ovary intact Wistar rats (3 months old) at the dose of 5 mg/kg during 30 days. Estradiol was used as a positive control. In intact females, daidzein disrupted the estrous cycle and female sexual behaviour, decreased the number of follicles and corpora lutea, increased uterine","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg","noael_value":"35","page":67,"route":"","species":"rat","study_id":"sccs_o_263_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 50 | mg/kg/day | - | - | 13 weeks | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=50; DOSE=ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test.; EFFECT=ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test. When comparing the NOELs/LOELs of genistein for different exposure durations there was no apparent difference after 4 and 13 weeks. The treatment-related findings would be expected to occur with a compound with intrinsic estrogenic activity. The no observed adverse effect level (NOAEL) of genistein is considered to be between 5 and 50 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. In a clinical trial by Bitto et al. (2010), genistein aglycone (54 mg) or placebo was given daily to osteopenic post-menopausal women for 24 months. A sub-cohort then continued therapy for an additional 12 months to evaluate the thyroid (THR α and THR β) and retinoid (RAR α, RAR γ, and RXR α) hormone receptors, mRNAs and the levels of thyro; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test.","duration":"13 weeks","effect":"ne dependent tissues (e.g., ovaries, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test. When comparing the NOELs/LOELs of genistein for different exposure durations there was no apparent difference after 4 and 13 weeks. The treatment-related findings would be expected to occur with a compound with intrinsic estrogenic activity. The no observed adverse effect level (NOAEL) of genistein is considered to be between 5 and 50 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. In a clinical trial by Bitto et al. (2010), genistein aglycone (54 mg) or placebo was given daily to osteopenic post-menopausal women for 24 months. A sub-cohort then continued therapy for an additional 12 months to evaluate the thyroid (THR α and THR β) and retinoid (RAR α, RAR γ, and RXR α) hormone receptors, mRNAs and the levels of thyro","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"50","page":60,"route":"","species":"","study_id":"sccs_o_263_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 50 | mg/kg/day | - | - | 13 weeks | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=50; DOSE=s, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test.; EFFECT=s, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test. When comparing the NOELs/LOELs of genistein for different exposure durations there was no apparent difference after 4 and 13 weeks. The treatment-related findings would be expected to occur with a compound with intrinsic estrogenic activity. The no observed adverse effect level (NOAEL) of genistein is considered to be between 5 and 50 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. In a clinical trial by Bitto et al. (2010), genistein aglycone (54 mg) or placebo was given daily to osteopenic post-menopausal women for 24 months. A sub-cohort then continued therapy for an additional 12 months to evaluate the thyroid (THR α and THR β) and retinoid (RAR α, RAR γ, and RXR α) hormone receptors, mRNAs and the levels of thyroid pero; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"s, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test.","duration":"13 weeks","effect":"s, uterus, vagina, mammary gland, testes), in sexual development (time to vaginal opening) and in fertility parameters (number of life pups) at dose levels clearly lower than those leading to slight effects in the ‘‘enhanced TG 407’’ test. When comparing the NOELs/LOELs of genistein for different exposure durations there was no apparent difference after 4 and 13 weeks. The treatment-related findings would be expected to occur with a compound with intrinsic estrogenic activity. The no observed adverse effect level (NOAEL) of genistein is considered to be between 5 and 50 mg/kg/day based on the hormonally induced functional changes at the higher dose due to the expected endocrine effects. In a clinical trial by Bitto et al. (2010), genistein aglycone (54 mg) or placebo was given daily to osteopenic post-menopausal women for 24 months. A sub-cohort then continued therapy for an additional 12 months to evaluate the thyroid (THR α and THR β) and retinoid (RAR α, RAR γ, and RXR α) hormone receptors, mRNAs and the levels of thyroid pero","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"","noael_unit":"mg/kg/day","noael_value":"50","page":60,"route":"","species":"","study_id":"sccs_o_263_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | ppm | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=100; DOSE=SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.; LOAEL_VALUE=20 mg/kg bw; EFFECT=iders that only the studies performed with pure daidzein are relevant for safety assessment as a cosmetic ingredient. SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these studies, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) in the current assessment.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.","duration":"developmental","effect":"iders that only the studies performed with pure daidzein are relevant for safety assessment as a cosmetic ingredient. SCCS overall comments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these studies, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) in the current assessment.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"20 mg/kg bw","noael_unit":"ppm","noael_value":"100","page":37,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | ppm | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=100; DOSE=ments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.; LOAEL_VALUE=20 mg/kg bw; EFFECT=ments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these studies, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) in the current assessment.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"ments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.","duration":"developmental","effect":"ments on reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these studies, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) in the current assessment.","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"20 mg/kg bw","noael_unit":"ppm","noael_value":"100","page":37,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | ppm | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=100; DOSE=_______________________________________________________________ _______________________________________________________________________ 75 Reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights...; LOAEL_VALUE=20 mg/kg bw; EFFECT=_______________________________________________________________ _______________________________________________________________________ 75 Reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) for genistein in the current assessment. Daidzein Only studies publi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"_______________________________________________________________ _______________________________________________________________________ 75 Reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights...","duration":"developmental","effect":"_______________________________________________________________ _______________________________________________________________________ 75 Reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) for genistein in the current assessment. Daidzein Only studies publi","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"20 mg/kg bw","noael_unit":"ppm","noael_value":"100","page":75,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_034"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | ppm | rat | oral | developmental | reproductive toxicity | SOURCE_SUBDIR=sccs_o_263; REPORT_TITLE=OPINION on Genistein and Daidzein; OPINION_NUMBER=SCCS/1641/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 16 September 2022; VALUE_TEXT=100; DOSE=__ 75 Reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.; LOAEL_VALUE=20 mg/kg bw; EFFECT=__ 75 Reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) for genistein in the current assessment. Daidzein Only studies published in the literature were used by SCCS, but the original study reports were not available. Based on the observed effects in the most; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"446-72-0","citation":"","dose":"__ 75 Reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration.","duration":"developmental","effect":"__ 75 Reproductive toxicity Genistein The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration. From the relevant toxicological studies, the SCCS regarded it reasonable to consider that a NOAEL for genistein aglycone is between 5 and 100 ppm. A recent report by the Nordic Council of Ministers (2020) has used 100 ppm as a NOAEL from the NCTR study for pregnant women (equivalent to 8.9 mg/kg bw). However, the same report used 100 ppm as a LOAEL for children (equivalent to 20 mg/kg bw) from a study by Li et al. (2014). In view of these, the SCCS considered it pragmatic to use 100 ppm as a LOAEL for the calculation of Margin of Safety (MoS) for genistein in the current assessment. Daidzein Only studies published in the literature were used by SCCS, but the original study reports were not available. Based on the observed effects in the most","endpoint":"reproductive toxicity","ingredient":"codes ............................................... 10","loael_value":"20 mg/kg bw","noael_unit":"ppm","noael_value":"100","page":75,"route":"oral","species":"rat","study_id":"sccs_o_263_noael_035"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | DH2M523P0H | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C15H10O5","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"DH2M523P0H"} |
| openFDA substances | FDA UNII substance identifier | DH2M523P0H | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C15H10O5","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"DH2M523P0H"} |
| openFDA substances | FDA UNII substance identifier | DH2M523P0H | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C15H10O5","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"DH2M523P0H"} |
| openFDA substances | FDA UNII substance identifier | DH2M523P0H | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C15H10O5","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"DH2M523P0H"} |