NOAEL Studies
Cosmetic Ingredient
Phenyl Methyl Pyrazolone NOAEL Studies
INCI: PHENYL METHYL PYRAZOLONE
CAS: 89-25-8
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
NTP_ICE_acute_oral 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_acute_oral | LD50 | =1915 | mg/kg bw | Rat | oral | acute | Rat Acute Oral Toxicity | NLM ChemIDplus TEST (undated); record_id=acute_oral_11168; row=15371; data_type=In Vivo; mixture=Chemical; chemical_name=1-Phenyl-3-methyl-5-pyrazolone; preferred_name=1-Phenyl-3-methyl-5-pyrazolone; dtxsid=DTXSID9021130; url=https://chem.nlm.nih.gov/chemidplus/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID9021130; source_file=acute_oral.xlsx |
NTP_ICE_adme_parameters 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_adme_parameters | Clint | 2 | uL/min/10^6 cells | Human | - | - | Measured; httk, Human Hepatic Intrinsic Clearance | sheet=Data; excel_row=3536; Record_ID=adme_parameters_620; Data_Type=Measured; DTXSID=DTXSID9021130; Assay=httk, Human Hepatic Intrinsic Clearance; Endpoint=Clint; Response=2.0; Response_Unit=ul/min/10^6 cells; Species=Human; Reference=httk2.3.1, Williamson 2020; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_adme_parameters | Fu | 0.89 | fraction | Human | - | - | Measured; httk, Human Plasma Fraction Unbound | sheet=Data; excel_row=3535; Record_ID=adme_parameters_620; Data_Type=Measured; DTXSID=DTXSID9021130; Assay=httk, Human Plasma Fraction Unbound; Endpoint=Fu; Response=0.89; Response_Unit=Unitless Fraction; Species=Human; Reference=httk2.3.1, Lombardo 2018; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
NTP_ICE_cancer 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_cancer | Top dose | 5000 | ppm | Rat | - | - | In Vivo; NTP Carcinogenicity | sheet=Data; excel_row=9813; Record_ID=cancer_4694; Data_Type=In Vivo; Formulation_Name=1-Phenyl-3-methyl-5-pyrazolone; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=NTP Carcinogenicity; Endpoint=Top dose; Response=5000; Response_Unit=ppm; Species=Rat; Strain=F344/N; Sex=Female; Reference=TR-141; URL=https://ntp.niehs.nih.gov/publications/reports/tr/100s/tr141/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_cancer | Top dose | 15000 | ppm | Mouse | - | - | In Vivo; NTP Carcinogenicity | sheet=Data; excel_row=9817; Record_ID=cancer_4691; Data_Type=In Vivo; Formulation_Name=1-Phenyl-3-methyl-5-pyrazolone; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=NTP Carcinogenicity; Endpoint=Top dose; Response=15000; Response_Unit=ppm; Species=Mouse; Strain=B6C3F1; Sex=Female; Reference=TR-141; URL=https://ntp.niehs.nih.gov/publications/reports/tr/100s/tr141/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
NTP_ICE_skin_sensitization 8 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_skin_sensitization | CV75 | 417 | ug/mL | - | Dermal | - | In Vitro; Urbisch_SkinSensitization2020; h-CLAT | sheet=Data_invitro; excel_row=1666; Record_ID=skin_sensitization_invitro_459; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=h-CLAT; Endpoint=CV75; Reported_Response=417; Reported_Response_Unit=ug/mL; Response=417; Response_Unit=ug/mL; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_skin_sensitization | EC1.5 | 4000 | uM | - | Dermal | - | In Vitro; Urbisch_SkinSensitization2020; KeratinoSens | sheet=Data_invitro; excel_row=6875; Record_ID=skin_sensitization_invitro_1628; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=4000; Reported_Response_Unit=uM; Response=4000; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_skin_sensitization | EC3 | 8.5 | % | Mouse | Dermal | - | In Vivo; Urbisch_SkinSensitization2020; LLNA | sheet=Data_invivo; excel_row=12933; Record_ID=skin_sensitization_invivo_2862; Data_Type=In Vivo; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=LLNA; Endpoint=EC3; Response=8.5; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_skin_sensitization | EC3 | 8.3 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13451; Record_ID=skin_sensitization_invivo_3601; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=LLNA; Endpoint=EC3; Response=8.3; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kern et al. 2010; 20137736; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_skin_sensitization | EC3 | 8.3 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13451; Record_ID=skin_sensitization_invivo_3601; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=LLNA; Endpoint=EC3; Response=8.3; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kern et al. 2010; 20137736; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_skin_sensitization | EC3 | 8.3 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13451; Record_ID=skin_sensitization_invivo_3601; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=LLNA; Endpoint=EC3; Response=8.3; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kern et al. 2010; 20137736; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_skin_sensitization | EC3 | 8.3 | % | Mouse | Dermal | - | In Vivo; LLNAdb2013; LLNA | sheet=Data_invivo; excel_row=13451; Record_ID=skin_sensitization_invivo_3601; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=LLNA; Endpoint=EC3; Response=8.3; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kern et al. 2010; 20137736; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
| NTP_ICE_skin_sensitization | Imax | 1.2 | ratio | - | Dermal | - | In Vitro; Urbisch_SkinSensitization2020; KeratinoSens | sheet=Data_invitro; excel_row=6878; Record_ID=skin_sensitization_invitro_1628; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021130; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=1.199586113; Reported_Response_Unit=Unitless; Response=1.2; Response_Unit=Ratio; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021130; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9021130 |
SCCS_vision_codex 28 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =0.003 | mg/kg bw | rat | dermal | 28-day | dermal absorption | {"dose":"With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg).","effect":"in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing maximal 0.25 % Norantipyrine). With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg). So a margin of safety of 66670 can be calculated between the figure for human exposure to oxidative hair dye and the no effect level found in rats in the 28-day study. It should be noted that the NOAEL stems from a daily exposure for 28 days, whereas human exposure to permanent hair dye is unlikely to be more than once a month. Need for an adequate sensitization test.” Submission II for this substance was submitted in July 1997 by COLIPA². Submission III for this substance was submitted in November 1998 by COLIPA². The Scientific Committee on Cosmetics on Non-Food Products (SCCNFP) adopted at the plenary meeting on 23 June 1999 the opinion (SCCNFP/0134/99) on phenyl methyl pyrazolone with the opinion: “The SC","page":5,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_001"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg/day | - | - | Chronic | NOAEL study | {"citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels.","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels. Plasma levels were comparable after single dosing and at the end of the dosing period. The Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity","page":15,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_002"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw | rat | - | Chronic | genotoxicity | {"citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level.","effect":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA1535, TA1537, TA98, TA100 and TA102 Replicates: Triplicates per concentration in two independent experiments both in the presence and absence of Aroclor 1254 induced rat liver S9 Assay conditions: Direct plate incorporation me","page":15,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg/day | human | - | developmental | developmental toxicity | {"citation":"Ref.: 14 3","dose":"In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group.","effect":"roups pregnancy. In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group. No parental macroscopic changes were seen. There were no treatment-related foetal external or skeletal abnormalities. No foetal soft tissue anomalies were observed in any group. At 1000 mg/kg/day, maternal toxic effects were observed and associated with lower foetal weight and increased incidence of foetuses with reduced ossification. There were no teratogenic effects, and the NOAEL was 200 mg/kg/day for both maternal and developmental toxicity. Ref.: 14 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":24,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | rat | oral | 13-week | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SA...","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SAS x A x 0.001/60 = 0.012 No observed adverse effect level NOAEL = 100 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 8333 3.3.14. Discussion Physico-chemical specification Phenyl methyl pyrazolone is used in oxidative hair dye formulations at a maximum concentration of 0.5%, which after mixing typically in 1:1 ratio with hydrogen peroxide prior to use, corresponds to a concentration of 0.25% upon application. Stability of phenyl methyl pyrazolone in marketed products is not reported General toxicity PMP is not acutely toxic. The median lethal dose (LD5","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | oral | 13 weeks | developmental toxicity | {"dose":"The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg.","effect":"acutely toxic. The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg. 4 different vehicles were used. The repeated daily oral administration of PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to hav","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_008"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg/day | rat | dermal | 13 weeks | developmental toxicity | {"dose":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day.","effect":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to have a strong sensitising potential. Dermal absorption The amounts of phenylmethyl pyrazolone considered as absorbed from a hair colouring formulation containing","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_010"} |
| SCCS_vision_codex | NOAEL | =0.003 | mg/kg bw | rat | dermal | 28-day | dermal absorption | {"dose":"With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg).","effect":"in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing maximal 0.25 % Norantipyrine). With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg). So a margin of safety of 66670 can be calculated between the figure for human exposure to oxidative hair dye and the no effect level found in rats in the 28-day study. It should be noted that the NOAEL stems from a daily exposure for 28 days, whereas human exposure to permanent hair dye is unlikely to be more than once a month. Need for an adequate sensitization test.” Submission II for this substance was submitted in July 1997 by COLIPA². Submission III for this substance was submitted in November 1998 by COLIPA². The Scientific Committee on Cosmetics on Non-Food Products (SCCNFP) adopted at the plenary meeting on 23 June 1999 the opinion (SCCNFP/0134/99) on phenyl methyl pyrazolone with the opinion: “The SC","page":5,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_001"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg/day | - | - | Chronic | NOAEL study | {"citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels.","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels. Plasma levels were comparable after single dosing and at the end of the dosing period. The Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity","page":15,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_002"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw | rat | - | Chronic | genotoxicity | {"citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level.","effect":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA1535, TA1537, TA98, TA100 and TA102 Replicates: Triplicates per concentration in two independent experiments both in the presence and absence of Aroclor 1254 induced rat liver S9 Assay conditions: Direct plate incorporation me","page":15,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg/day | human | - | developmental | developmental toxicity | {"citation":"Ref.: 14 3","dose":"In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group.","effect":"roups pregnancy. In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group. No parental macroscopic changes were seen. There were no treatment-related foetal external or skeletal abnormalities. No foetal soft tissue anomalies were observed in any group. At 1000 mg/kg/day, maternal toxic effects were observed and associated with lower foetal weight and increased incidence of foetuses with reduced ossification. There were no teratogenic effects, and the NOAEL was 200 mg/kg/day for both maternal and developmental toxicity. Ref.: 14 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":24,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | rat | oral | 13-week | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SA...","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SAS x A x 0.001/60 = 0.012 No observed adverse effect level NOAEL = 100 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 8333 3.3.14. Discussion Physico-chemical specification Phenyl methyl pyrazolone is used in oxidative hair dye formulations at a maximum concentration of 0.5%, which after mixing typically in 1:1 ratio with hydrogen peroxide prior to use, corresponds to a concentration of 0.25% upon application. Stability of phenyl methyl pyrazolone in marketed products is not reported General toxicity PMP is not acutely toxic. The median lethal dose (LD5","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | oral | 13 weeks | developmental toxicity | {"dose":"The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg.","effect":"acutely toxic. The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg. 4 different vehicles were used. The repeated daily oral administration of PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to hav","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_008"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg/day | rat | dermal | 13 weeks | developmental toxicity | {"dose":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day.","effect":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to have a strong sensitising potential. Dermal absorption The amounts of phenylmethyl pyrazolone considered as absorbed from a hair colouring formulation containing","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_010"} |
| SCCS_vision_codex | NOAEL | =0.003 | mg/kg bw | rat | dermal | 28-day | dermal absorption | {"dose":"With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg).","effect":"in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing maximal 0.25 % Norantipyrine). With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg). So a margin of safety of 66670 can be calculated between the figure for human exposure to oxidative hair dye and the no effect level found in rats in the 28-day study. It should be noted that the NOAEL stems from a daily exposure for 28 days, whereas human exposure to permanent hair dye is unlikely to be more than once a month. Need for an adequate sensitization test.” Submission II for this substance was submitted in July 1997 by COLIPA². Submission III for this substance was submitted in November 1998 by COLIPA². The Scientific Committee on Cosmetics on Non-Food Products (SCCNFP) adopted at the plenary meeting on 23 June 1999 the opinion (SCCNFP/0134/99) on phenyl methyl pyrazolone with the opinion: “The SC","page":5,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_001"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg/day | - | - | Chronic | NOAEL study | {"citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels.","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels. Plasma levels were comparable after single dosing and at the end of the dosing period. The Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity","page":15,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_002"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw | rat | - | Chronic | genotoxicity | {"citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level.","effect":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA1535, TA1537, TA98, TA100 and TA102 Replicates: Triplicates per concentration in two independent experiments both in the presence and absence of Aroclor 1254 induced rat liver S9 Assay conditions: Direct plate incorporation me","page":15,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg/day | human | - | developmental | developmental toxicity | {"citation":"Ref.: 14 3","dose":"In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group.","effect":"roups pregnancy. In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group. No parental macroscopic changes were seen. There were no treatment-related foetal external or skeletal abnormalities. No foetal soft tissue anomalies were observed in any group. At 1000 mg/kg/day, maternal toxic effects were observed and associated with lower foetal weight and increased incidence of foetuses with reduced ossification. There were no teratogenic effects, and the NOAEL was 200 mg/kg/day for both maternal and developmental toxicity. Ref.: 14 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":24,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | rat | oral | 13-week | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SA...","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SAS x A x 0.001/60 = 0.012 No observed adverse effect level NOAEL = 100 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 8333 3.3.14. Discussion Physico-chemical specification Phenyl methyl pyrazolone is used in oxidative hair dye formulations at a maximum concentration of 0.5%, which after mixing typically in 1:1 ratio with hydrogen peroxide prior to use, corresponds to a concentration of 0.25% upon application. Stability of phenyl methyl pyrazolone in marketed products is not reported General toxicity PMP is not acutely toxic. The median lethal dose (LD5","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | oral | 13 weeks | developmental toxicity | {"dose":"The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg.","effect":"acutely toxic. The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg. 4 different vehicles were used. The repeated daily oral administration of PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to hav","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_008"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg/day | rat | dermal | 13 weeks | developmental toxicity | {"dose":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day.","effect":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to have a strong sensitising potential. Dermal absorption The amounts of phenylmethyl pyrazolone considered as absorbed from a hair colouring formulation containing","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_010"} |
| SCCS_vision_codex | NOAEL | =0.003 | mg/kg bw | rat | dermal | 28-day | dermal absorption | {"dose":"With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg).","effect":"in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing maximal 0.25 % Norantipyrine). With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg). So a margin of safety of 66670 can be calculated between the figure for human exposure to oxidative hair dye and the no effect level found in rats in the 28-day study. It should be noted that the NOAEL stems from a daily exposure for 28 days, whereas human exposure to permanent hair dye is unlikely to be more than once a month. Need for an adequate sensitization test.” Submission II for this substance was submitted in July 1997 by COLIPA². Submission III for this substance was submitted in November 1998 by COLIPA². The Scientific Committee on Cosmetics on Non-Food Products (SCCNFP) adopted at the plenary meeting on 23 June 1999 the opinion (SCCNFP/0134/99) on phenyl methyl pyrazolone with the opinion: “The SC","page":5,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_001"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg/day | - | - | Chronic | NOAEL study | {"citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels.","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels. Plasma levels were comparable after single dosing and at the end of the dosing period. The Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity","page":15,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_002"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw | rat | - | Chronic | genotoxicity | {"citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level.","effect":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA1535, TA1537, TA98, TA100 and TA102 Replicates: Triplicates per concentration in two independent experiments both in the presence and absence of Aroclor 1254 induced rat liver S9 Assay conditions: Direct plate incorporation me","page":15,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_003"} |
| SCCS_vision_codex | NOAEL | =200 | mg/kg/day | human | - | developmental | developmental toxicity | {"citation":"Ref.: 14 3","dose":"In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group.","effect":"roups pregnancy. In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group. No parental macroscopic changes were seen. There were no treatment-related foetal external or skeletal abnormalities. No foetal soft tissue anomalies were observed in any group. At 1000 mg/kg/day, maternal toxic effects were observed and associated with lower foetal weight and increased incidence of foetuses with reduced ossification. There were no teratogenic effects, and the NOAEL was 200 mg/kg/day for both maternal and developmental toxicity. Ref.: 14 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":24,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | rat | oral | 13-week | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SA...","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SAS x A x 0.001/60 = 0.012 No observed adverse effect level NOAEL = 100 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 8333 3.3.14. Discussion Physico-chemical specification Phenyl methyl pyrazolone is used in oxidative hair dye formulations at a maximum concentration of 0.5%, which after mixing typically in 1:1 ratio with hydrogen peroxide prior to use, corresponds to a concentration of 0.25% upon application. Stability of phenyl methyl pyrazolone in marketed products is not reported General toxicity PMP is not acutely toxic. The median lethal dose (LD5","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg/day | rat | oral | 13 weeks | developmental toxicity | {"dose":"The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg.","effect":"acutely toxic. The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg. 4 different vehicles were used. The repeated daily oral administration of PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to hav","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_008"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg/day | rat | dermal | 13 weeks | developmental toxicity | {"dose":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day.","effect":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to have a strong sensitising potential. Dermal absorption The amounts of phenylmethyl pyrazolone considered as absorbed from a hair colouring formulation containing","page":25,"pdf":"sccp_o_087.pdf","row_type":"noael_study","study_id":"sccp_o_087_noael_010"} |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 10 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20 | mg/kg/day | - | - | Chronic | - | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=20; DOSE=SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels.; EFFECT=SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels. Plasma levels were comparable after single dosing and at the end of the dosing period. The Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity; CITATION=Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher; CITATION_NUMBERS=[6,100]; REFERENCE=Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher; DETAILS_JSON={"cas_number":"89-25-8","citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels.","duration":"Chronic","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 15 PMP was detected in the plasma at all dose levels. Plasma levels were comparable after single dosing and at the end of the dosing period. The Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity","endpoint":"","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg/day","noael_value":"20","page":15,"route":"","species":"","study_id":"sccp_o_087_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 0.003 | mg/kg bw | rat | dermal | 28-day | dermal absorption | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=0.003; DOSE=With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg).; EFFECT=in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing maximal 0.25 % Norantipyrine). With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg). So a margin of safety of 66670 can be calculated between the figure for human exposure to oxidative hair dye and the no effect level found in rats in the 28-day study. It should be noted that the NOAEL stems from a daily exposure for 28 days, whereas human exposure to permanent hair dye is unlikely to be more than once a month. Need for an adequate sensitization test.” Submission II for this substance was submitted in July 1997 by COLIPA². Submission III for this substance was submitted in November 1998 by COLIPA². The Scientific Committee on Cosmetics on Non-Food Products (SCCNFP) adopted at the plenary meeting on 23 June 1999 the opinion (SCCNFP/0134/99) on phenyl methyl pyrazolone with the opinion: “The SC; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"89-25-8","citation":"","dose":"With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg).","duration":"28-day","effect":"in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing maximal 0.25 % Norantipyrine). With a maximal penetration, under normal condition, of 0.08 %, this results in a dermal absorption of 0.2 mg per treatment, which is 0.003 mg/kg bw (assuming a body weight of 60 kg). So a margin of safety of 66670 can be calculated between the figure for human exposure to oxidative hair dye and the no effect level found in rats in the 28-day study. It should be noted that the NOAEL stems from a daily exposure for 28 days, whereas human exposure to permanent hair dye is unlikely to be more than once a month. Need for an adequate sensitization test.” Submission II for this substance was submitted in July 1997 by COLIPA². Submission III for this substance was submitted in November 1998 by COLIPA². The Scientific Committee on Cosmetics on Non-Food Products (SCCNFP) adopted at the plenary meeting on 23 June 1999 the opinion (SCCNFP/0134/99) on phenyl methyl pyrazolone with the opinion: “The SC","endpoint":"dermal absorption","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg bw","noael_value":"0.003","page":5,"route":"dermal","species":"rat","study_id":"sccp_o_087_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | =100 | mg/kg bw | rat | oral | 13-week | dermal absorption | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT== 100; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SA...; EFFECT=SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SAS x A x 0.001/60 = 0.012 No observed adverse effect level NOAEL = 100 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 8333 3.3.14. Discussion Physico-chemical specification Phenyl methyl pyrazolone is used in oxidative hair dye formulations at a maximum concentration of 0.5%, which after mixing typically in 1:1 ratio with hydrogen peroxide prior to use, corresponds to a concentration of 0.25% upon application. Stability of phenyl methyl pyrazolone in marketed products is not reported General toxicity PMP is not acutely toxic. The median lethal dose (LD5; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"89-25-8","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SA...","duration":"13-week","effect":"SCCP/1033/06 OPINION ON PHENYL METHYL PYRAZOLONE 25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SAS x A x 0.001/60 = 0.012 No observed adverse effect level NOAEL = 100 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 8333 3.3.14. Discussion Physico-chemical specification Phenyl methyl pyrazolone is used in oxidative hair dye formulations at a maximum concentration of 0.5%, which after mixing typically in 1:1 ratio with hydrogen peroxide prior to use, corresponds to a concentration of 0.25% upon application. Stability of phenyl methyl pyrazolone in marketed products is not reported General toxicity PMP is not acutely toxic. The median lethal dose (LD5","endpoint":"dermal absorption","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 100","page":25,"route":"oral","species":"rat","study_id":"sccp_o_087_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | =100 | mg/kg bw | rat | oral | 13-week | dermal absorption | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT== 100; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SA...; EFFECT=6 OPINION ON PHENYL METHYL PYRAZOLONE 25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SAS x A x 0.001/60 = 0.012 No observed adverse effect level NOAEL = 100 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 8333 3.3.14. Discussion Physico-chemical specification Phenyl methyl pyrazolone is used in oxidative hair dye formulations at a maximum concentration of 0.5%, which after mixing typically in 1:1 ratio with hydrogen peroxide prior to use, corresponds to a concentration of 0.25% upon application. Stability of phenyl methyl pyrazolone in marketed products is not reported General toxicity PMP is not acutely toxic. The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg. 4 different vehicles; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"89-25-8","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SA...","duration":"13-week","effect":"6 OPINION ON PHENYL METHYL PYRAZOLONE 25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (phenyl methyl pyrazolone) (Oxidative/permanent) Maximum absorption through the skin A = 1.01 µg/cm² Skin Area surface SAS = 700 Dermal absorption per treatment SAS x A x 0.001 = 0.707 mg Typical body weight of human = 60 kg Systemic exposure dosage (SED) SAS x A x 0.001/60 = 0.012 No observed adverse effect level NOAEL = 100 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 8333 3.3.14. Discussion Physico-chemical specification Phenyl methyl pyrazolone is used in oxidative hair dye formulations at a maximum concentration of 0.5%, which after mixing typically in 1:1 ratio with hydrogen peroxide prior to use, corresponds to a concentration of 0.25% upon application. Stability of phenyl methyl pyrazolone in marketed products is not reported General toxicity PMP is not acutely toxic. The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg. 4 different vehicles","endpoint":"dermal absorption","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 100","page":25,"route":"oral","species":"rat","study_id":"sccp_o_087_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 200 | mg/kg/day | human | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group.; EFFECT=roups pregnancy. In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group. No parental macroscopic changes were seen. There were no treatment-related foetal external or skeletal abnormalities. No foetal soft tissue anomalies were observed in any group. At 1000 mg/kg/day, maternal toxic effects were observed and associated with lower foetal weight and increased incidence of foetuses with reduced ossification. There were no teratogenic effects, and the NOAEL was 200 mg/kg/day for both maternal and developmental toxicity. Ref.: 14 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted; CITATION=Ref.: 14 3; CITATION_NUMBERS=[14,3]; REFERENCE=Ref.: 14 3; DETAILS_JSON={"cas_number":"89-25-8","citation":"Ref.: 14 3","dose":"In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group.","duration":"developmental","effect":"roups pregnancy. In the 1000 mg/kg/day, the body weight gain of the dams during the treatment period was 8% less than in the control group. No parental macroscopic changes were seen. There were no treatment-related foetal external or skeletal abnormalities. No foetal soft tissue anomalies were observed in any group. At 1000 mg/kg/day, maternal toxic effects were observed and associated with lower foetal weight and increased incidence of foetuses with reduced ossification. There were no teratogenic effects, and the NOAEL was 200 mg/kg/day for both maternal and developmental toxicity. Ref.: 14 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","endpoint":"developmental toxicity","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg/day","noael_value":"200","page":24,"route":"","species":"human","study_id":"sccp_o_087_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 100 | mg/kg/day | rat | oral | 13 weeks | developmental toxicity | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=100; DOSE=The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg.; EFFECT=acutely toxic. The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg. 4 different vehicles were used. The repeated daily oral administration of PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to hav; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"89-25-8","citation":"","dose":"The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg.","duration":"13 weeks","effect":"acutely toxic. The median lethal dose (LD50) of PMP was consistently above 2000 mg/kg. 4 different vehicles were used. The repeated daily oral administration of PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to hav","endpoint":"developmental toxicity","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":25,"route":"oral","species":"rat","study_id":"sccp_o_087_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 100 | mg/kg/day | rat | oral | 13 weeks | developmental toxicity | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=100; DOSE=f PMP was consistently above 2000 mg/kg.; EFFECT=f PMP was consistently above 2000 mg/kg. 4 different vehicles were used. The repeated daily oral administration of PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to have a strong sensitising potential. Dermal abs; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"89-25-8","citation":"","dose":"f PMP was consistently above 2000 mg/kg.","duration":"13 weeks","effect":"f PMP was consistently above 2000 mg/kg. 4 different vehicles were used. The repeated daily oral administration of PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to have a strong sensitising potential. Dermal abs","endpoint":"developmental toxicity","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":25,"route":"oral","species":"rat","study_id":"sccp_o_087_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | 1000 | mg/kg/day | rat | dermal | 13 weeks | developmental toxicity | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=1000; DOSE=f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day.; EFFECT=f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to have a strong sensitising potential. Dermal absorption The amounts of phenylmethyl pyrazolone considered as absorbed from a hair colouring formulation containing; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"89-25-8","citation":"","dose":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day.","duration":"13 weeks","effect":"f PMP to rats for 13 weeks at 20, 100, and 500 mg/kg/day was mainly associated with changes indicative of regenerative haemolytic anaemia at 500 mg/kg/day. Clinical signs attributed to PMP but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The NOAEL was determined to be 100 mg/kg/day. The NOEL was set at 20 mg/kg bw. PMP had no teratogenic potential. Maternal toxicity was seen at 1000 mg/kg/day. The NOAEL of maternal and developmental toxicity was 200 mg/kg/day. Irritation / sensitisation Under the conditions of the tests study, 1-phenyl-3-methyl-5-pyrazolone at 1% in propylene glycol caused transient mild irritation to rabbit skin. It was non-irritating to rabbit eyes. Phenylmethyl pyrazolone induced delayed contact hypersensitivity. It is considered to have a strong sensitising potential. Dermal absorption The amounts of phenylmethyl pyrazolone considered as absorbed from a hair colouring formulation containing","endpoint":"developmental toxicity","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":25,"route":"dermal","species":"rat","study_id":"sccp_o_087_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | genotoxicity | 20 | mg/kg bw | rat | - | Chronic | genotoxicity | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=20; DOSE=Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level.; EFFECT=Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA1535, TA1537, TA98, TA100 and TA102 Replicates: Triplicates per concentration in two independent experiments both in the presence and absence of Aroclor 1254 induced rat liver S9 Assay conditions: Direct plate incorporation me; CITATION=Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher; CITATION_NUMBERS=[6,100]; REFERENCE=Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher; DETAILS_JSON={"cas_number":"89-25-8","citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level.","duration":"Chronic","effect":"Cmax was measured 0.5 h after dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA1535, TA1537, TA98, TA100 and TA102 Replicates: Triplicates per concentration in two independent experiments both in the presence and absence of Aroclor 1254 induced rat liver S9 Assay conditions: Direct plate incorporation me","endpoint":"genotoxicity","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg bw","noael_value":"20","page":15,"route":"","species":"rat","study_id":"sccp_o_087_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | genotoxicity | 20 | mg/kg bw | rat | - | Chronic | genotoxicity | SOURCE_SUBDIR=sccp_o_087; REPORT_TITLE=OPINION ON PHENYL METHYL PYRAZOLONE COLIPA N° A39; OPINION_NUMBER=SCCP/1033/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=20; DOSE=dosing, and systemic exposure increased with dose level.; EFFECT=dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA1535, TA1537, TA98, TA100 and TA102 Replicates: Triplicates per concentration in two independent experiments both in the presence and absence of Aroclor 1254 induced rat liver S9 Assay conditions: Direct plate incorporation method, apart from the second test; CITATION=Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher; CITATION_NUMBERS=[6,100]; REFERENCE=Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher; DETAILS_JSON={"cas_number":"89-25-8","citation":"Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher","dose":"dosing, and systemic exposure increased with dose level.","duration":"Chronic","effect":"dosing, and systemic exposure increased with dose level. The NOAEL of the study was 20 mg/kg/day, a dose level associated in week 13 with systemic exposure (AUC 0-24) values of 4.3 µg.h/ml in males and 15.1 µg.h/ml in females. Ref.: 6 Comment Clinical signs attributed to phenyl methyl pyrazolone but related to the mode of administration were observed at 100 mg/kg/day and higher. In males, the exposure of 100 mg/kg/day resulted in lower blood levels of glucose. The SCCP considers the NOEL to be 20 mg/kg bw and the NOAEL to be 100 mg/kg bw. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA1535, TA1537, TA98, TA100 and TA102 Replicates: Triplicates per concentration in two independent experiments both in the presence and absence of Aroclor 1254 induced rat liver S9 Assay conditions: Direct plate incorporation method, apart from the second test","endpoint":"genotoxicity","ingredient":"Phenyl methyl pyrazolone","loael_value":"","noael_unit":"mg/kg bw","noael_value":"20","page":15,"route":"","species":"rat","study_id":"sccp_o_087_noael_004"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | S798V6YJRP | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C10H10N2O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S798V6YJRP"} |
| openFDA substances | FDA UNII substance identifier | S798V6YJRP | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C10H10N2O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S798V6YJRP"} |
| openFDA substances | FDA UNII substance identifier | S798V6YJRP | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C10H10N2O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S798V6YJRP"} |
| openFDA substances | FDA UNII substance identifier | S798V6YJRP | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C10H10N2O","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S798V6YJRP"} |