NOAEL Studies
Active Ingredient
Beta-Arbutin NOAEL Studies
INCI: BETA-ARBUTIN
CAS: 497-76-7
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
SCCS_vision_codex 80 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | {"citation":"Ref.: 10 3","dose":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species.","effect":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species. Necropsy at the end of the dosing period revealed some spontaneous anomalies, but no test compound-related changes. There were no histopathological findings related to administration of the test substance. Conclusion The study authors conclude that, since no changes attributed to β-arbutin were observed up to a dosage of 1000 mg/kg bw/day, the latter can be considered as the NOEL value. Ref.: 10 3.3.5.2 Sub-chronic (90 days) dermal toxicity Guideline: Not stated, though mainly according to Annex V to Dir. 67/548/EEC, Method B.28: Repeated dose (90 days) toxicity (dermal), OECD Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents Date of test: September - November 1986 Species/strain: Sprague Dawley rat (SPF Crj:CD) Group size: 10 animals/sex/dosage group Test substance: β-arbutin dissolved in 50% aqueous ethanol solution (vehicle) Batch: Lot A Purity: 99.7% Dosages: 0 (untr","page":17,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_001"} |
| SCCS_vision_codex | NOAEL | =618 | mg/kg bw/day | - | oral | 28 day | NOAEL study | {"citation":"Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the a","dose":"56 mg/kg/day within the normal range of variation (no dose-dependency observed).","effect":"56 mg/kg/day within the normal range of variation (no dose-dependency observed). The same is claimed for the increased monocyte ratio (618 mg/kg bw/day) and the decreased Ca++ level in females (294 mg/kg bw/day), which are regarded as being within normal physiological variation. Conclusion The study authors conclude that, since no test substance-related changes attributed to β-arbutin were observed up to a dosage of 618 mg/kg bw/day (the maximum technically applicable dosage), the latter can be considered as the NOEL value. Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. 3.3.5.3 Chronic (≥ 12 months) toxicity No data.","page":18,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_002"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | - | 28 day | repeated dose toxicity | {"citation":"Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats)","dose":"Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice.","effect":"spleen, calcification in brain thalamus, subcapsular hyperplasia in the adrenal gland, ovary cysts, cystoic endometrial hyperplasia in the uterus and detachment or hypertrophy of articular chondrocytes in the joint. Tumour lesions included hepatocellular adenoma, bronchiolar/alveolar adenoma and malignant lymphoma. These lesions occurred in all groups (also in the control group). Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice. It is also concluded that the test substance is not carcinogenic under the conditions of the performed study. Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats). In addition, the weight variation in the animals at the beginning of the study exceeded 20% (± 50%) and the intermediate haematological examinatio","page":21,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_003"} |
| SCCS_vision_codex | NOAEL | =0.522 | µg/cm | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Posi","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) i","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_005"} |
| SCCS_vision_codex | NOAEL | =74 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivoca","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_006"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage le","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_007"} |
| SCCS_vision_codex | NOAEL | =75 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"citation":"Ref.: 26, 29 Hydroquinone has been used for many year","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many year","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_008"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"citation":"Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"ns Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%. It does not directly bleach the skin,","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_009"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | dermal | - | reproductive toxicity | {"dose":"Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin.","effect":"the presence of metabolic activation system in the presented in vitro mammalian chromosome aberration test. Therefore β-arbutin is considered to be non-mutagenic. Not all three tests as mentioned in the SCCP Notes of Guidance have been presented. Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin. Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day. Photo-induced adverse effects The presented summaries of a phototoxicity and photosensitisation assay with β-arbutin in the guinea pig conclude that the substance displays neither photototoxic nor photoallergic potential. The human repeated open application test with so-called \"exposure to sunlight\" lacks stan","page":33,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_011"} |
| SCCS_vision_codex | NOAEL | =150 | mg/kg/day | rat | - | - | reproductive toxicity | {"dose":"NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","effect":"Unlabeled table on page 30: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_017"} |
| SCCS_vision_codex | NOAEL | =1550 | - | - | - | - | reproductive toxicity | {"citation":"Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 29 Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; yet, subcutaneous injection is an uncommon application route in one-generation reproductive toxicity tests. 3.3.8.2 Teratogenicity No data submitted. 3.3.9 Toxicokinetics ß-Arbutin is hydrolysed into hydroquinone and glucose in the presence of weak acids. Cosmetics with ß-arbutin may contain small amounts of hydroquinone (HQ) as impurity. Hydrolysis of dermally applied arbutin may also occur to some extent on the skin surface (by microflora) and in the skin (by hydrolases). Data on skin metab","page":29,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_005"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/ kg bw | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 8)","dose":"3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref.","effect":"butin. For the safety evaluation of HQ exposure resulting from the use of skin bleaching products in comparison to internal HQ doses which may induce ochronosis, the SCCS will use 50% dermal absorption for HQ. 3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref. 8). The no observed effect level (NOEL) from the 28-day oral toxicity rat study (ref. 10) of 1000 mg/ kg bw was adjusted by a factor of 3 for time. Absorption through the skin A = 0.339 µg/cm² Skin Area surface SAS = 565 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.192 mg (x 2) Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0064 mg/kg bw","page":36,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_012"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg bw/d | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considera","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_013"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considerations will focus on ingredient-related exposure to hydroquinone as resulting from topical application of β-arbutin. Safety","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_014"} |
| SCCS_vision_codex | NOAEL | =0.0005 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","effect":"ef. 8) is absorbed or 240 µg/person/day (internal); – the fraction of HQ in skin, relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) –","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_015"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","effect":"relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_016"} |
| SCCS_vision_codex | NOAEL | =0.00076 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e.","effect":"/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e. 1.6 g creme), one may add 1.6 µg HQ (external) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day The internal HQ exposure amounts to 45.8 µg per day; divided by 60 kg body weight SED = 0.763 µg/kg bw/d or 0.00076 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 19737 or 26315","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_017"} |
| SCCS_vision_codex | NOAEL | =1 | % | - | - | - | NOAEL study | {"dose":"As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis:","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 38 2. For exogenous ochronosis HQ is suspected to cause exogenous ochronosis. As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis: 1% has been adopted as the minimum exposure level of HQ causing EO since no publication available suggests EO with products formulated with 1% or less HQ. Exposure Dose of HQ that may cause ochronosis was calculated as 8 mg/day [1 x 0.8 x 1000 x 2 x 50 / 100 x 100] – Lowest concentration in product 1% – Maximum quantity of application","page":38,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_019"} |
| SCCS_vision_codex | NOAEL | =37 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 37: NOAEL / SED results in MOS of 19737 or 26315","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_029"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | {"citation":"Ref.: 10 3","dose":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species.","effect":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species. Necropsy at the end of the dosing period revealed some spontaneous anomalies, but no test compound-related changes. There were no histopathological findings related to administration of the test substance. Conclusion The study authors conclude that, since no changes attributed to β-arbutin were observed up to a dosage of 1000 mg/kg bw/day, the latter can be considered as the NOEL value. Ref.: 10 3.3.5.2 Sub-chronic (90 days) dermal toxicity Guideline: Not stated, though mainly according to Annex V to Dir. 67/548/EEC, Method B.28: Repeated dose (90 days) toxicity (dermal), OECD Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents Date of test: September - November 1986 Species/strain: Sprague Dawley rat (SPF Crj:CD) Group size: 10 animals/sex/dosage group Test substance: β-arbutin dissolved in 50% aqueous ethanol solution (vehicle) Batch: Lot A Purity: 99.7% Dosages: 0 (untr","page":17,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_001"} |
| SCCS_vision_codex | NOAEL | =618 | mg/kg bw/day | - | oral | 28 day | NOAEL study | {"citation":"Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the a","dose":"56 mg/kg/day within the normal range of variation (no dose-dependency observed).","effect":"56 mg/kg/day within the normal range of variation (no dose-dependency observed). The same is claimed for the increased monocyte ratio (618 mg/kg bw/day) and the decreased Ca++ level in females (294 mg/kg bw/day), which are regarded as being within normal physiological variation. Conclusion The study authors conclude that, since no test substance-related changes attributed to β-arbutin were observed up to a dosage of 618 mg/kg bw/day (the maximum technically applicable dosage), the latter can be considered as the NOEL value. Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. 3.3.5.3 Chronic (≥ 12 months) toxicity No data.","page":18,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_002"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | - | 28 day | repeated dose toxicity | {"citation":"Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats)","dose":"Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice.","effect":"spleen, calcification in brain thalamus, subcapsular hyperplasia in the adrenal gland, ovary cysts, cystoic endometrial hyperplasia in the uterus and detachment or hypertrophy of articular chondrocytes in the joint. Tumour lesions included hepatocellular adenoma, bronchiolar/alveolar adenoma and malignant lymphoma. These lesions occurred in all groups (also in the control group). Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice. It is also concluded that the test substance is not carcinogenic under the conditions of the performed study. Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats). In addition, the weight variation in the animals at the beginning of the study exceeded 20% (± 50%) and the intermediate haematological examinatio","page":21,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_003"} |
| SCCS_vision_codex | NOAEL | =0.522 | µg/cm | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Posi","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) i","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_005"} |
| SCCS_vision_codex | NOAEL | =74 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivoca","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_006"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage le","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_007"} |
| SCCS_vision_codex | NOAEL | =75 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"citation":"Ref.: 26, 29 Hydroquinone has been used for many year","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many year","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_008"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"citation":"Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"ns Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%. It does not directly bleach the skin,","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_009"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | dermal | - | reproductive toxicity | {"dose":"Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin.","effect":"the presence of metabolic activation system in the presented in vitro mammalian chromosome aberration test. Therefore β-arbutin is considered to be non-mutagenic. Not all three tests as mentioned in the SCCP Notes of Guidance have been presented. Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin. Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day. Photo-induced adverse effects The presented summaries of a phototoxicity and photosensitisation assay with β-arbutin in the guinea pig conclude that the substance displays neither photototoxic nor photoallergic potential. The human repeated open application test with so-called \"exposure to sunlight\" lacks stan","page":33,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_011"} |
| SCCS_vision_codex | NOAEL | =150 | mg/kg/day | rat | - | - | reproductive toxicity | {"dose":"NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","effect":"Unlabeled table on page 30: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_017"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | {"citation":"Ref.: 10 3","dose":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species.","effect":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species. Necropsy at the end of the dosing period revealed some spontaneous anomalies, but no test compound-related changes. There were no histopathological findings related to administration of the test substance. Conclusion The study authors conclude that, since no changes attributed to β-arbutin were observed up to a dosage of 1000 mg/kg bw/day, the latter can be considered as the NOEL value. Ref.: 10 3.3.5.2 Sub-chronic (90 days) dermal toxicity Guideline: Not stated, though mainly according to Annex V to Dir. 67/548/EEC, Method B.28: Repeated dose (90 days) toxicity (dermal), OECD Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents Date of test: September - November 1986 Species/strain: Sprague Dawley rat (SPF Crj:CD) Group size: 10 animals/sex/dosage group Test substance: β-arbutin dissolved in 50% aqueous ethanol solution (vehicle) Batch: Lot A Purity: 99.7% Dosages: 0 (untr","page":17,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_001"} |
| SCCS_vision_codex | NOAEL | =618 | mg/kg bw/day | - | oral | 28 day | NOAEL study | {"citation":"Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the a","dose":"56 mg/kg/day within the normal range of variation (no dose-dependency observed).","effect":"56 mg/kg/day within the normal range of variation (no dose-dependency observed). The same is claimed for the increased monocyte ratio (618 mg/kg bw/day) and the decreased Ca++ level in females (294 mg/kg bw/day), which are regarded as being within normal physiological variation. Conclusion The study authors conclude that, since no test substance-related changes attributed to β-arbutin were observed up to a dosage of 618 mg/kg bw/day (the maximum technically applicable dosage), the latter can be considered as the NOEL value. Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. 3.3.5.3 Chronic (≥ 12 months) toxicity No data.","page":18,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_002"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | - | 28 day | repeated dose toxicity | {"citation":"Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats)","dose":"Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice.","effect":"spleen, calcification in brain thalamus, subcapsular hyperplasia in the adrenal gland, ovary cysts, cystoic endometrial hyperplasia in the uterus and detachment or hypertrophy of articular chondrocytes in the joint. Tumour lesions included hepatocellular adenoma, bronchiolar/alveolar adenoma and malignant lymphoma. These lesions occurred in all groups (also in the control group). Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice. It is also concluded that the test substance is not carcinogenic under the conditions of the performed study. Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats). In addition, the weight variation in the animals at the beginning of the study exceeded 20% (± 50%) and the intermediate haematological examinatio","page":21,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_003"} |
| SCCS_vision_codex | NOAEL | =0.522 | µg/cm | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Posi","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) i","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_005"} |
| SCCS_vision_codex | NOAEL | =74 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivoca","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_006"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage le","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_007"} |
| SCCS_vision_codex | NOAEL | =75 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"citation":"Ref.: 26, 29 Hydroquinone has been used for many year","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many year","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_008"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"citation":"Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"ns Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%. It does not directly bleach the skin,","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_009"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | dermal | - | reproductive toxicity | {"dose":"Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin.","effect":"the presence of metabolic activation system in the presented in vitro mammalian chromosome aberration test. Therefore β-arbutin is considered to be non-mutagenic. Not all three tests as mentioned in the SCCP Notes of Guidance have been presented. Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin. Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day. Photo-induced adverse effects The presented summaries of a phototoxicity and photosensitisation assay with β-arbutin in the guinea pig conclude that the substance displays neither photototoxic nor photoallergic potential. The human repeated open application test with so-called \"exposure to sunlight\" lacks stan","page":33,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_011"} |
| SCCS_vision_codex | NOAEL | =150 | mg/kg/day | rat | - | - | reproductive toxicity | {"dose":"NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","effect":"Unlabeled table on page 30: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_017"} |
| SCCS_vision_codex | NOAEL | =1550 | - | - | - | - | reproductive toxicity | {"citation":"Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 29 Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; yet, subcutaneous injection is an uncommon application route in one-generation reproductive toxicity tests. 3.3.8.2 Teratogenicity No data submitted. 3.3.9 Toxicokinetics ß-Arbutin is hydrolysed into hydroquinone and glucose in the presence of weak acids. Cosmetics with ß-arbutin may contain small amounts of hydroquinone (HQ) as impurity. Hydrolysis of dermally applied arbutin may also occur to some extent on the skin surface (by microflora) and in the skin (by hydrolases). Data on skin metab","page":29,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_005"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/ kg bw | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 8)","dose":"3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref.","effect":"butin. For the safety evaluation of HQ exposure resulting from the use of skin bleaching products in comparison to internal HQ doses which may induce ochronosis, the SCCS will use 50% dermal absorption for HQ. 3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref. 8). The no observed effect level (NOEL) from the 28-day oral toxicity rat study (ref. 10) of 1000 mg/ kg bw was adjusted by a factor of 3 for time. Absorption through the skin A = 0.339 µg/cm² Skin Area surface SAS = 565 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.192 mg (x 2) Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0064 mg/kg bw","page":36,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_012"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg bw/d | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considera","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_013"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considerations will focus on ingredient-related exposure to hydroquinone as resulting from topical application of β-arbutin. Safety","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_014"} |
| SCCS_vision_codex | NOAEL | =0.0005 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","effect":"ef. 8) is absorbed or 240 µg/person/day (internal); – the fraction of HQ in skin, relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) –","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_015"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","effect":"relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_016"} |
| SCCS_vision_codex | NOAEL | =0.00076 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e.","effect":"/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e. 1.6 g creme), one may add 1.6 µg HQ (external) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day The internal HQ exposure amounts to 45.8 µg per day; divided by 60 kg body weight SED = 0.763 µg/kg bw/d or 0.00076 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 19737 or 26315","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_017"} |
| SCCS_vision_codex | NOAEL | =1 | % | - | - | - | NOAEL study | {"dose":"As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis:","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 38 2. For exogenous ochronosis HQ is suspected to cause exogenous ochronosis. As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis: 1% has been adopted as the minimum exposure level of HQ causing EO since no publication available suggests EO with products formulated with 1% or less HQ. Exposure Dose of HQ that may cause ochronosis was calculated as 8 mg/day [1 x 0.8 x 1000 x 2 x 50 / 100 x 100] – Lowest concentration in product 1% – Maximum quantity of application","page":38,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_019"} |
| SCCS_vision_codex | NOAEL | =37 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 37: NOAEL / SED results in MOS of 19737 or 26315","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_029"} |
| SCCS_vision_codex | NOAEL | =1550 | - | - | - | - | reproductive toxicity | {"citation":"Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 29 Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; yet, subcutaneous injection is an uncommon application route in one-generation reproductive toxicity tests. 3.3.8.2 Teratogenicity No data submitted. 3.3.9 Toxicokinetics ß-Arbutin is hydrolysed into hydroquinone and glucose in the presence of weak acids. Cosmetics with ß-arbutin may contain small amounts of hydroquinone (HQ) as impurity. Hydrolysis of dermally applied arbutin may also occur to some extent on the skin surface (by microflora) and in the skin (by hydrolases). Data on skin metab","page":29,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_005"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/ kg bw | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 8)","dose":"3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref.","effect":"butin. For the safety evaluation of HQ exposure resulting from the use of skin bleaching products in comparison to internal HQ doses which may induce ochronosis, the SCCS will use 50% dermal absorption for HQ. 3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref. 8). The no observed effect level (NOEL) from the 28-day oral toxicity rat study (ref. 10) of 1000 mg/ kg bw was adjusted by a factor of 3 for time. Absorption through the skin A = 0.339 µg/cm² Skin Area surface SAS = 565 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.192 mg (x 2) Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0064 mg/kg bw","page":36,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_012"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg bw/d | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considera","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_013"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considerations will focus on ingredient-related exposure to hydroquinone as resulting from topical application of β-arbutin. Safety","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_014"} |
| SCCS_vision_codex | NOAEL | =0.0005 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","effect":"ef. 8) is absorbed or 240 µg/person/day (internal); – the fraction of HQ in skin, relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) –","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_015"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","effect":"relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_016"} |
| SCCS_vision_codex | NOAEL | =0.00076 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e.","effect":"/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e. 1.6 g creme), one may add 1.6 µg HQ (external) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day The internal HQ exposure amounts to 45.8 µg per day; divided by 60 kg body weight SED = 0.763 µg/kg bw/d or 0.00076 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 19737 or 26315","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_017"} |
| SCCS_vision_codex | NOAEL | =1 | % | - | - | - | NOAEL study | {"dose":"As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis:","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 38 2. For exogenous ochronosis HQ is suspected to cause exogenous ochronosis. As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis: 1% has been adopted as the minimum exposure level of HQ causing EO since no publication available suggests EO with products formulated with 1% or less HQ. Exposure Dose of HQ that may cause ochronosis was calculated as 8 mg/day [1 x 0.8 x 1000 x 2 x 50 / 100 x 100] – Lowest concentration in product 1% – Maximum quantity of application","page":38,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_019"} |
| SCCS_vision_codex | NOAEL | =37 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 37: NOAEL / SED results in MOS of 19737 or 26315","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_029"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | {"citation":"Ref.: 10 3","dose":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species.","effect":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species. Necropsy at the end of the dosing period revealed some spontaneous anomalies, but no test compound-related changes. There were no histopathological findings related to administration of the test substance. Conclusion The study authors conclude that, since no changes attributed to β-arbutin were observed up to a dosage of 1000 mg/kg bw/day, the latter can be considered as the NOEL value. Ref.: 10 3.3.5.2 Sub-chronic (90 days) dermal toxicity Guideline: Not stated, though mainly according to Annex V to Dir. 67/548/EEC, Method B.28: Repeated dose (90 days) toxicity (dermal), OECD Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents Date of test: September - November 1986 Species/strain: Sprague Dawley rat (SPF Crj:CD) Group size: 10 animals/sex/dosage group Test substance: β-arbutin dissolved in 50% aqueous ethanol solution (vehicle) Batch: Lot A Purity: 99.7% Dosages: 0 (untr","page":17,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_001"} |
| SCCS_vision_codex | NOAEL | =618 | mg/kg bw/day | - | oral | 28 day | NOAEL study | {"citation":"Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the a","dose":"56 mg/kg/day within the normal range of variation (no dose-dependency observed).","effect":"56 mg/kg/day within the normal range of variation (no dose-dependency observed). The same is claimed for the increased monocyte ratio (618 mg/kg bw/day) and the decreased Ca++ level in females (294 mg/kg bw/day), which are regarded as being within normal physiological variation. Conclusion The study authors conclude that, since no test substance-related changes attributed to β-arbutin were observed up to a dosage of 618 mg/kg bw/day (the maximum technically applicable dosage), the latter can be considered as the NOEL value. Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. 3.3.5.3 Chronic (≥ 12 months) toxicity No data.","page":18,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_002"} |
| SCCS_vision_codex | NOAEL | =400 | mg/kg bw/day | rat | - | 28 day | repeated dose toxicity | {"citation":"Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats)","dose":"Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice.","effect":"spleen, calcification in brain thalamus, subcapsular hyperplasia in the adrenal gland, ovary cysts, cystoic endometrial hyperplasia in the uterus and detachment or hypertrophy of articular chondrocytes in the joint. Tumour lesions included hepatocellular adenoma, bronchiolar/alveolar adenoma and malignant lymphoma. These lesions occurred in all groups (also in the control group). Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice. It is also concluded that the test substance is not carcinogenic under the conditions of the performed study. Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats). In addition, the weight variation in the animals at the beginning of the study exceeded 20% (± 50%) and the intermediate haematological examinatio","page":21,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_003"} |
| SCCS_vision_codex | NOAEL | =0.522 | µg/cm | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Posi","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_004"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) i","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_005"} |
| SCCS_vision_codex | NOAEL | =74 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivoca","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_006"} |
| SCCS_vision_codex | NOAEL | =25 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage le","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_007"} |
| SCCS_vision_codex | NOAEL | =75 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"citation":"Ref.: 26, 29 Hydroquinone has been used for many year","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many year","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_008"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg/day | rat | oral | 28d | reproductive toxicity | {"citation":"Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","effect":"ns Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%. It does not directly bleach the skin,","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_009"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | dermal | - | reproductive toxicity | {"dose":"Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin.","effect":"the presence of metabolic activation system in the presented in vitro mammalian chromosome aberration test. Therefore β-arbutin is considered to be non-mutagenic. Not all three tests as mentioned in the SCCP Notes of Guidance have been presented. Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin. Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day. Photo-induced adverse effects The presented summaries of a phototoxicity and photosensitisation assay with β-arbutin in the guinea pig conclude that the substance displays neither photototoxic nor photoallergic potential. The human repeated open application test with so-called \"exposure to sunlight\" lacks stan","page":33,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_011"} |
| SCCS_vision_codex | NOAEL | =150 | mg/kg/day | rat | - | - | reproductive toxicity | {"dose":"NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","effect":"Unlabeled table on page 30: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","page":30,"pdf":"sccp_o_134.pdf","row_type":"noael_study","study_id":"sccp_o_134_noael_017"} |
| SCCS_vision_codex | NOAEL | =1550 | - | - | - | - | reproductive toxicity | {"citation":"Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 29 Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; yet, subcutaneous injection is an uncommon application route in one-generation reproductive toxicity tests. 3.3.8.2 Teratogenicity No data submitted. 3.3.9 Toxicokinetics ß-Arbutin is hydrolysed into hydroquinone and glucose in the presence of weak acids. Cosmetics with ß-arbutin may contain small amounts of hydroquinone (HQ) as impurity. Hydrolysis of dermally applied arbutin may also occur to some extent on the skin surface (by microflora) and in the skin (by hydrolases). Data on skin metab","page":29,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_005"} |
| SCCS_vision_codex | NOAEL | =1000 | mg/ kg bw | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 8)","dose":"3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref.","effect":"butin. For the safety evaluation of HQ exposure resulting from the use of skin bleaching products in comparison to internal HQ doses which may induce ochronosis, the SCCS will use 50% dermal absorption for HQ. 3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref. 8). The no observed effect level (NOEL) from the 28-day oral toxicity rat study (ref. 10) of 1000 mg/ kg bw was adjusted by a factor of 3 for time. Absorption through the skin A = 0.339 µg/cm² Skin Area surface SAS = 565 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.192 mg (x 2) Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0064 mg/kg bw","page":36,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_012"} |
| SCCS_vision_codex | NOAEL | =333 | mg/kg bw/d | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considera","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_013"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw | rat | oral | 28-day | dermal absorption | {"citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considerations will focus on ingredient-related exposure to hydroquinone as resulting from topical application of β-arbutin. Safety","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_014"} |
| SCCS_vision_codex | NOAEL | =0.0005 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","effect":"ef. 8) is absorbed or 240 µg/person/day (internal); – the fraction of HQ in skin, relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) –","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_015"} |
| SCCS_vision_codex | NOAEL | =20 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","effect":"relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_016"} |
| SCCS_vision_codex | NOAEL | =0.00076 | mg/kg bw/d | - | dermal | - | dermal absorption | {"citation":"(ref. 9)","dose":"9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e.","effect":"/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e. 1.6 g creme), one may add 1.6 µg HQ (external) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day The internal HQ exposure amounts to 45.8 µg per day; divided by 60 kg body weight SED = 0.763 µg/kg bw/d or 0.00076 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 19737 or 26315","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_017"} |
| SCCS_vision_codex | NOAEL | =1 | % | - | - | - | NOAEL study | {"dose":"As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis:","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 38 2. For exogenous ochronosis HQ is suspected to cause exogenous ochronosis. As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis: 1% has been adopted as the minimum exposure level of HQ causing EO since no publication available suggests EO with products formulated with 1% or less HQ. Exposure Dose of HQ that may cause ochronosis was calculated as 8 mg/day [1 x 0.8 x 1000 x 2 x 50 / 100 x 100] – Lowest concentration in product 1% – Maximum quantity of application","page":38,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_019"} |
| SCCS_vision_codex | NOAEL | =37 | - | - | - | - | NOAEL study | {"effect":"Unlabeled table on page 37: NOAEL / SED results in MOS of 19737 or 26315","page":37,"pdf":"sccs_o_169.pdf","row_type":"noael_study","study_id":"sccs_o_169_noael_029"} |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 46 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 618 | mg/kg bw/day | - | oral | 28 day | - | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT=618; DOSE=56 mg/kg/day within the normal range of variation (no dose-dependency observed).; EFFECT=56 mg/kg/day within the normal range of variation (no dose-dependency observed). The same is claimed for the increased monocyte ratio (618 mg/kg bw/day) and the decreased Ca++ level in females (294 mg/kg bw/day), which are regarded as being within normal physiological variation. Conclusion The study authors conclude that, since no test substance-related changes attributed to β-arbutin were observed up to a dosage of 618 mg/kg bw/day (the maximum technically applicable dosage), the latter can be considered as the NOEL value. Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. 3.3.5.3 Chronic (≥ 12 months) toxicity No data.; CITATION=Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the a; CITATION_NUMBERS=[11,28]; REFERENCE=Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the a; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the a","dose":"56 mg/kg/day within the normal range of variation (no dose-dependency observed).","duration":"28 day","effect":"56 mg/kg/day within the normal range of variation (no dose-dependency observed). The same is claimed for the increased monocyte ratio (618 mg/kg bw/day) and the decreased Ca++ level in females (294 mg/kg bw/day), which are regarded as being within normal physiological variation. Conclusion The study authors conclude that, since no test substance-related changes attributed to β-arbutin were observed up to a dosage of 618 mg/kg bw/day (the maximum technically applicable dosage), the latter can be considered as the NOEL value. Ref.: 11 Remark The evolution of the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28 day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. 3.3.5.3 Chronic (≥ 12 months) toxicity No data.","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"618","page":18,"route":"oral","species":"","study_id":"sccp_o_134_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =20 | mg/kg/day | rat | oral | 28d | - | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 20; DOSE=NOEL (28d/90d-oral-rat) = 20 mg/kg/day; EFFECT=Unlabeled table on page 30: NOEL (28d/90d-oral-rat) = 20 mg/kg/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (28d/90d-oral-rat) = 20 mg/kg/day","duration":"28d","effect":"Unlabeled table on page 30: NOEL (28d/90d-oral-rat) = 20 mg/kg/day","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 20","page":30,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =74 | mg/kg/day | rat | dermal | 28d | - | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 74; DOSE=NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day; EFFECT=Unlabeled table on page 30: NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day","duration":"28d","effect":"Unlabeled table on page 30: NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 74","page":30,"route":"dermal","species":"rat","study_id":"sccp_o_134_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =15 | mg/kg/day | rat | - | - | - | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 15; DOSE=NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).; EFFECT=Unlabeled table on page 30: NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).","duration":"","effect":"Unlabeled table on page 30: NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 15","page":30,"route":"","species":"rat","study_id":"sccp_o_134_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1 | % | - | - | - | - | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=1; DOSE=As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis:; EFFECT=SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 38 2. For exogenous ochronosis HQ is suspected to cause exogenous ochronosis. As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis: 1% has been adopted as the minimum exposure level of HQ causing EO since no publication available suggests EO with products formulated with 1% or less HQ. Exposure Dose of HQ that may cause ochronosis was calculated as 8 mg/day [1 x 0.8 x 1000 x 2 x 50 / 100 x 100] – Lowest concentration in product 1% – Maximum quantity of application; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis:","duration":"","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 38 2. For exogenous ochronosis HQ is suspected to cause exogenous ochronosis. As a NOAEL has not been established for exogenous ochronosis (EO), the lowest effect level described in a case report was used to calculate the Exposure Dose of HQ that might cause ochronosis: 1% has been adopted as the minimum exposure level of HQ causing EO since no publication available suggests EO with products formulated with 1% or less HQ. Exposure Dose of HQ that may cause ochronosis was calculated as 8 mg/day [1 x 0.8 x 1000 x 2 x 50 / 100 x 100] – Lowest concentration in product 1% – Maximum quantity of application","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"%","noael_value":"1","page":38,"route":"","species":"","study_id":"sccs_o_169_noael_019"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =20 | mg/kg/day | rat | oral | 28d | - | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 20; DOSE=NOEL (28d/90d-oral-rat) = 20 mg/kg/day; EFFECT=Unlabeled table on page 35: NOEL (28d/90d-oral-rat) = 20 mg/kg/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (28d/90d-oral-rat) = 20 mg/kg/day","duration":"28d","effect":"Unlabeled table on page 35: NOEL (28d/90d-oral-rat) = 20 mg/kg/day","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 20","page":35,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_022"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =74 | mg/kg/day | rat | dermal | 28d | - | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 74; DOSE=NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day; EFFECT=Unlabeled table on page 35: NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day","duration":"28d","effect":"Unlabeled table on page 35: NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 74","page":35,"route":"dermal","species":"rat","study_id":"sccs_o_169_noael_023"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | =15 | mg/kg/day | rat | - | - | - | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 15; DOSE=NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).; EFFECT=Unlabeled table on page 35: NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).","duration":"","effect":"Unlabeled table on page 35: NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 15","page":35,"route":"","species":"rat","study_id":"sccs_o_169_noael_026"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 20 | mg/kg bw/d | - | - | - | - | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=20; DOSE=NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d; EFFECT=Unlabeled table on page 37: NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d","duration":"","effect":"Unlabeled table on page 37: NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"20","page":37,"route":"","species":"","study_id":"sccs_o_169_noael_028"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 37 | - | - | - | - | - | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=unclear:Unlabeled table on page 37: NOAEL / SED results in MOS of 19737 or 26315; EFFECT=Unlabeled table on page 37: NOAEL / SED results in MOS of 19737 or 26315; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 37: NOAEL / SED results in MOS of 19737 or 26315","endpoint":"","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 37: NOAEL / SED results in MOS of 19737 or 26315","page":37,"route":"","species":"","study_id":"sccs_o_169_noael_029"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 1000 | mg/ kg bw | rat | oral | 28-day | dermal absorption | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=1000; DOSE=3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref.; EFFECT=butin. For the safety evaluation of HQ exposure resulting from the use of skin bleaching products in comparison to internal HQ doses which may induce ochronosis, the SCCS will use 50% dermal absorption for HQ. 3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref. 8). The no observed effect level (NOEL) from the 28-day oral toxicity rat study (ref. 10) of 1000 mg/ kg bw was adjusted by a factor of 3 for time. Absorption through the skin A = 0.339 µg/cm² Skin Area surface SAS = 565 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.192 mg (x 2) Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0064 mg/kg bw; CITATION=(ref. 8); CITATION_NUMBERS=[8]; REFERENCE=(ref. 8); DETAILS_JSON={"cas_number":"497-76-7","citation":"(ref. 8)","dose":"3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref.","duration":"28-day","effect":"butin. For the safety evaluation of HQ exposure resulting from the use of skin bleaching products in comparison to internal HQ doses which may induce ochronosis, the SCCS will use 50% dermal absorption for HQ. 3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for ß-arbutin (7% a.i. in face creams, applied 2 times per day) The systemic exposure dose (SED) was calculated for µg/cm2 derived from the in vitro dermal penetration study (ref. 8). The no observed effect level (NOEL) from the 28-day oral toxicity rat study (ref. 10) of 1000 mg/ kg bw was adjusted by a factor of 3 for time. Absorption through the skin A = 0.339 µg/cm² Skin Area surface SAS = 565 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.192 mg (x 2) Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0064 mg/kg bw","endpoint":"dermal absorption","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/ kg bw","noael_value":"1000","page":36,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_012"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | =333 | mg/kg bw/d | rat | oral | 28-day | dermal absorption | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 333; DOSE=3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.; EFFECT=SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considera; CITATION=(ref. 15); CITATION_NUMBERS=[15]; REFERENCE=(ref. 15); DETAILS_JSON={"cas_number":"497-76-7","citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","duration":"28-day","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considera","endpoint":"dermal absorption","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 333","page":37,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_013"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 100 | mg/kg bw | rat | oral | 28-day | dermal absorption | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=100; DOSE=3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.; EFFECT=SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considerations will focus on ingredient-related exposure to hydroquinone as resulting from topical application of β-arbutin. Safety; CITATION=(ref. 15); CITATION_NUMBERS=[15]; REFERENCE=(ref. 15); DETAILS_JSON={"cas_number":"497-76-7","citation":"(ref. 15)","dose":"3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref.","duration":"28-day","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 37 No observed effect level NOEL for 28-day, oral, rat : 3 = 333 mg/kg bw/d Margin of Safety NOEL/SED = 52082 Additional MOS calculations for the NOAEL of 100 mg/kg bw from the rat reprotoxicity study with subcutaneous administration (ref. 15) also arrive at very high value (MOS=15625). An SED calculation based on a dermal absorption of 0.214% of dose (instead of µg/cm2) arrives at 0.004 mg/kg bw (lower than the 0.0064 mg/kg bw above). Accordingly, the MoS values for ß-arbutin would be even higher (83250 and 25000). Further safety considerations will focus on ingredient-related exposure to hydroquinone as resulting from topical application of β-arbutin. Safety","endpoint":"dermal absorption","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw","noael_value":"100","page":37,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 0.0005 | mg/kg bw/d | - | dermal | - | dermal absorption | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=0.0005; DOSE=9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.; EFFECT=ef. 8) is absorbed or 240 µg/person/day (internal); – the fraction of HQ in skin, relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) –; CITATION=(ref. 9); CITATION_NUMBERS=[9]; REFERENCE=(ref. 9); DETAILS_JSON={"cas_number":"497-76-7","citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","duration":"","effect":"ef. 8) is absorbed or 240 µg/person/day (internal); – the fraction of HQ in skin, relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) –","endpoint":"dermal absorption","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0005","page":37,"route":"dermal","species":"","study_id":"sccs_o_169_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 20 | mg/kg bw/d | - | dermal | - | dermal absorption | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=20; DOSE=9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.; EFFECT=relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i; CITATION=(ref. 9); CITATION_NUMBERS=[9]; REFERENCE=(ref. 9); DETAILS_JSON={"cas_number":"497-76-7","citation":"(ref. 9)","dose":"9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day.","duration":"","effect":"relative to total absorbed, was up 12 parts (11.8% ref. 9) or in total 29 µg HQ. – For a possible presence of HQ as impurity (<1 ppm) in the applied product, one may add another 1.6 µg HQ (if 1 ppm in 1.6 g product as worst case) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day. The internal HQ exposure amounts to ≤31 µg per day; divided by 60 kg body weight = (SED) 0.517 µg/kg bw/d or 0.0005 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 25000 or 33333 B) Exposure to hydroquinone (HQ) from application of products containing up to 7% β-arbutin (and its dermal absorption in µg/cm2 instead of % of dose) is derived as follows: – For ß-arbutin (see above) SED = 0.0064 mg/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i","endpoint":"dermal absorption","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"20","page":37,"route":"dermal","species":"","study_id":"sccs_o_169_noael_016"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 0.00076 | mg/kg bw/d | - | dermal | - | dermal absorption | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=0.00076; DOSE=9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e.; EFFECT=/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e. 1.6 g creme), one may add 1.6 µg HQ (external) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day The internal HQ exposure amounts to 45.8 µg per day; divided by 60 kg body weight SED = 0.763 µg/kg bw/d or 0.00076 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 19737 or 26315; CITATION=(ref. 9); CITATION_NUMBERS=[9]; REFERENCE=(ref. 9); DETAILS_JSON={"cas_number":"497-76-7","citation":"(ref. 9)","dose":"9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e.","duration":"","effect":"/kg bw/d or 6.4 µg/kg bw/d – the fraction of HQ in skin, relative to total absorbed, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e. 1.6 g creme), one may add 1.6 µg HQ (external) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day The internal HQ exposure amounts to 45.8 µg per day; divided by 60 kg body weight SED = 0.763 µg/kg bw/d or 0.00076 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 19737 or 26315","endpoint":"dermal absorption","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.00076","page":37,"route":"dermal","species":"","study_id":"sccs_o_169_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 20 | mg/kg bw/d | - | dermal | - | dermal absorption | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=20; DOSE=9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e.; EFFECT=d, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e. 1.6 g creme), one may add 1.6 µg HQ (external) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day The internal HQ exposure amounts to 45.8 µg per day; divided by 60 kg body weight SED = 0.763 µg/kg bw/d or 0.00076 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 19737 or 26315; CITATION=(ref. 9); CITATION_NUMBERS=[9]; REFERENCE=(ref. 9); DETAILS_JSON={"cas_number":"497-76-7","citation":"(ref. 9)","dose":"9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e.","duration":"","effect":"d, is up to 11.8% (ref. 9) which is equivalent to 0.755 µg/kg bw HQ (x 60 kg = 45 µg HQ per day) – For a possible presence of HQ as impurity (below 1 ppm) in the applied product (i.e. 1.6 g creme), one may add 1.6 µg HQ (external) and use 50% dermal absorption for HQ, resulting in an extra 0.8 µg HQ per day The internal HQ exposure amounts to 45.8 µg per day; divided by 60 kg body weight SED = 0.763 µg/kg bw/d or 0.00076 mg/kg bw/d NOAEL reported for HQ repeated toxicity (section 3.3.13) are 15 or 20 mg/kg bw/d NOAEL / SED results in MOS of 19737 or 26315","endpoint":"dermal absorption","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"20","page":37,"route":"dermal","species":"","study_id":"sccs_o_169_noael_018"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | =25 | mg/kg/day | rabbit | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 25; DOSE=NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams).; EFFECT=Unlabeled table on page 30: NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams).","duration":"developmental","effect":"Unlabeled table on page 30: NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams).","endpoint":"developmental toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 25","page":30,"route":"","species":"rabbit","study_id":"sccp_o_134_noael_014"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | =75 | mg/kg/day | rabbit | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 75; DOSE=NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).; EFFECT=Unlabeled table on page 30: NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).","duration":"developmental","effect":"Unlabeled table on page 30: NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).","endpoint":"developmental toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 75","page":30,"route":"","species":"rabbit","study_id":"sccp_o_134_noael_015"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | =25 | mg/kg/day | rabbit | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 25; DOSE=NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams); EFFECT=Unlabeled table on page 35: NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams)","duration":"developmental","effect":"Unlabeled table on page 35: NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams)","endpoint":"developmental toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 25","page":35,"route":"","species":"rabbit","study_id":"sccs_o_169_noael_024"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | developmental toxicity | =75 | mg/kg/day | rabbit | - | developmental | developmental toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 75; DOSE=NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).; EFFECT=Unlabeled table on page 35: NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).","duration":"developmental","effect":"Unlabeled table on page 35: NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).","endpoint":"developmental toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 75","page":35,"route":"","species":"rabbit","study_id":"sccs_o_169_noael_025"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 1000 | mg/kg bw/day | rat | oral | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT=1000; DOSE=no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species.; EFFECT=no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species. Necropsy at the end of the dosing period revealed some spontaneous anomalies, but no test compound-related changes. There were no histopathological findings related to administration of the test substance. Conclusion The study authors conclude that, since no changes attributed to β-arbutin were observed up to a dosage of 1000 mg/kg bw/day, the latter can be considered as the NOEL value. Ref.: 10 3.3.5.2 Sub-chronic (90 days) dermal toxicity Guideline: Not stated, though mainly according to Annex V to Dir. 67/548/EEC, Method B.28: Repeated dose (90 days) toxicity (dermal), OECD Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents Date of test: September - November 1986 Species/strain: Sprague Dawley rat (SPF Crj:CD) Group size: 10 animals/sex/dosage group Test substance: β-arbutin dissolved in 50% aqueous ethanol solution (vehicle) Batch: Lot A Purity: 99.7% Dosages: 0 (untr; CITATION=Ref.: 10 3; CITATION_NUMBERS=[10,3]; REFERENCE=Ref.: 10 3; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 10 3","dose":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species.","duration":"Sub-chronic","effect":"no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species. Necropsy at the end of the dosing period revealed some spontaneous anomalies, but no test compound-related changes. There were no histopathological findings related to administration of the test substance. Conclusion The study authors conclude that, since no changes attributed to β-arbutin were observed up to a dosage of 1000 mg/kg bw/day, the latter can be considered as the NOEL value. Ref.: 10 3.3.5.2 Sub-chronic (90 days) dermal toxicity Guideline: Not stated, though mainly according to Annex V to Dir. 67/548/EEC, Method B.28: Repeated dose (90 days) toxicity (dermal), OECD Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents Date of test: September - November 1986 Species/strain: Sprague Dawley rat (SPF Crj:CD) Group size: 10 animals/sex/dosage group Test substance: β-arbutin dissolved in 50% aqueous ethanol solution (vehicle) Batch: Lot A Purity: 99.7% Dosages: 0 (untr","endpoint":"repeated dose toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":17,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 400 | mg/kg bw/day | rat | - | 28 day | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT=400; DOSE=Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice.; EFFECT=spleen, calcification in brain thalamus, subcapsular hyperplasia in the adrenal gland, ovary cysts, cystoic endometrial hyperplasia in the uterus and detachment or hypertrophy of articular chondrocytes in the joint. Tumour lesions included hepatocellular adenoma, bronchiolar/alveolar adenoma and malignant lymphoma. These lesions occurred in all groups (also in the control group). Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice. It is also concluded that the test substance is not carcinogenic under the conditions of the performed study. Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats). In addition, the weight variation in the animals at the beginning of the study exceeded 20% (± 50%) and the intermediate haematological examinatio; CITATION=Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats); CITATION_NUMBERS=[14,28,90]; REFERENCE=Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats); DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats)","dose":"Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice.","duration":"28 day","effect":"spleen, calcification in brain thalamus, subcapsular hyperplasia in the adrenal gland, ovary cysts, cystoic endometrial hyperplasia in the uterus and detachment or hypertrophy of articular chondrocytes in the joint. Tumour lesions included hepatocellular adenoma, bronchiolar/alveolar adenoma and malignant lymphoma. These lesions occurred in all groups (also in the control group). Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for β-arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice. It is also concluded that the test substance is not carcinogenic under the conditions of the performed study. Ref.: 14 Remarks No rationale is given for the choice of another species than the one used in the 28 day or 90 day repeated dose study (mice instead of rats). In addition, the weight variation in the animals at the beginning of the study exceeded 20% (± 50%) and the intermediate haematological examinatio","endpoint":"repeated dose toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":21,"route":"","species":"rat","study_id":"sccp_o_134_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 1000 | mg/kg bw/day | rat | oral | 28 day | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT=1000; DOSE=Systemic toxicity The acute toxicity profile of β-arbutin can be considered low, viewing the LD50-oral-rat value of 8715 mg/kg/day and the LD50-dermal-rat of > 928 mg/kg (maximum practically applicable dosage).; EFFECT=n (6.3%) was slightly below the requested maximum concentration (7.0%). Systemic toxicity The acute toxicity profile of β-arbutin can be considered low, viewing the LD50-oral-rat value of 8715 mg/kg/day and the LD50-dermal-rat of > 928 mg/kg (maximum practically applicable dosage). A repeated dose 28 day oral study and 90 day dermal study with the rat only revealed some sporadic observations which could not be related to the test substance. Therefore in both tests, the highest dosage tested could be designated as NOEL, i.e. 1000 mg/kg bw/day for the repeated dose oral study and 618 mg/kg bw/day for the repeated dose dermal study. Toxicokinetics A human skin metabolism study revealed that daily topical application for 4 consecutive days of a gel containing 6.3% (w/w) β-arbutin led to detectable amounts of β-arbutin and HQ in skin. Based on a large variation in the established urinary total HQ results, changes in urinary HQ levels due to topical treatment of β-arbutin could not be established. When the HQ content in the skin sam; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"Systemic toxicity The acute toxicity profile of β-arbutin can be considered low, viewing the LD50-oral-rat value of 8715 mg/kg/day and the LD50-dermal-rat of > 928 mg/kg (maximum practically applicable dosage).","duration":"28 day","effect":"n (6.3%) was slightly below the requested maximum concentration (7.0%). Systemic toxicity The acute toxicity profile of β-arbutin can be considered low, viewing the LD50-oral-rat value of 8715 mg/kg/day and the LD50-dermal-rat of > 928 mg/kg (maximum practically applicable dosage). A repeated dose 28 day oral study and 90 day dermal study with the rat only revealed some sporadic observations which could not be related to the test substance. Therefore in both tests, the highest dosage tested could be designated as NOEL, i.e. 1000 mg/kg bw/day for the repeated dose oral study and 618 mg/kg bw/day for the repeated dose dermal study. Toxicokinetics A human skin metabolism study revealed that daily topical application for 4 consecutive days of a gel containing 6.3% (w/w) β-arbutin led to detectable amounts of β-arbutin and HQ in skin. Based on a large variation in the established urinary total HQ results, changes in urinary HQ levels due to topical treatment of β-arbutin could not be established. When the HQ content in the skin sam","endpoint":"repeated dose toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":32,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 1000 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=1000; DOSE=hough no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species.; EFFECT=hough no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species. Necropsy at the end of the dosing period revealed some spontaneous anomalies, but no test compound-related changes. There were no histopathological findings related to administration of the test substance. Conclusion The study authors conclude that, since no changes attributed to -arbutin were observed up to a dosage of 1000 mg/kg bw/day, this can be considered as the NOEL value. Ref.: 10 3.3.5.2 Sub-chronic (90 days) dermal toxicity Guideline: OECD Guideline 411: Repeated Dose 90-Day Dermal Toxicity Study in Rodents Date of test: February - May 1986 Species/strain: Sprague Dawley rat (SPF Crj:CD) Group size: 10 animals/sex/dosage group Test substance: -arbutin dissolved in 50% aqueous ethanol solution (vehicle) Batch: Lot A Purity: 99.7% Dosages: 0 (untreated) - 0 (vehicle) - 56 - 294 - 618 mg/kg bw/day in 2.0 mL/kg bw Observation period: 90 days GLP/QAU: / Prepared test subs; CITATION=Ref.: 10 3; CITATION_NUMBERS=[10,3]; REFERENCE=Ref.: 10 3; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 10 3","dose":"hough no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species.","duration":"Sub-chronic","effect":"hough no dose-dependency could be observed and the observed changes were small and reported to be within the normal ranges for the tested species. Necropsy at the end of the dosing period revealed some spontaneous anomalies, but no test compound-related changes. There were no histopathological findings related to administration of the test substance. Conclusion The study authors conclude that, since no changes attributed to -arbutin were observed up to a dosage of 1000 mg/kg bw/day, this can be considered as the NOEL value. Ref.: 10 3.3.5.2 Sub-chronic (90 days) dermal toxicity Guideline: OECD Guideline 411: Repeated Dose 90-Day Dermal Toxicity Study in Rodents Date of test: February - May 1986 Species/strain: Sprague Dawley rat (SPF Crj:CD) Group size: 10 animals/sex/dosage group Test substance: -arbutin dissolved in 50% aqueous ethanol solution (vehicle) Batch: Lot A Purity: 99.7% Dosages: 0 (untreated) - 0 (vehicle) - 56 - 294 - 618 mg/kg bw/day in 2.0 mL/kg bw Observation period: 90 days GLP/QAU: / Prepared test subs","endpoint":"repeated dose toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":23,"route":"dermal","species":"rat","study_id":"sccs_o_169_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 618 | mg/kg bw/day | rat | oral | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=618; DOSE=ght at 56 mg/kg/day within the normal range of variation (no dose-dependency observed).; EFFECT=ght at 56 mg/kg/day within the normal range of variation (no dose-dependency observed). The same is claimed for the increased monocyte ratio (618 mg/kg bw/day) and the decreased Ca2+ level in females (294 mg/kg bw/day), which are regarded as being within normal physiological variation. Conclusion The study authors conclude that, since no test substance-related changes attributed to -arbutin were observed up to a dosage of 618 mg/kg bw/day (the maximum technically applicable dosage), this can be considered as the NOEL value. Ref.: 11 SCCS comment The change in the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28-day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. SCCS conclusion on repeated dose toxicity A repeated dose 28-day oral study and 90-day dermal study with the rat only revealed some sporadic observations that could not be related to the test substance. Th; CITATION=Ref.: 11 SCCS comment The change in the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28-day oral study, supporting th; CITATION_NUMBERS=[11,28]; REFERENCE=Ref.: 11 SCCS comment The change in the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28-day oral study, supporting th; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 11 SCCS comment The change in the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28-day oral study, supporting th","dose":"ght at 56 mg/kg/day within the normal range of variation (no dose-dependency observed).","duration":"28-day","effect":"ght at 56 mg/kg/day within the normal range of variation (no dose-dependency observed). The same is claimed for the increased monocyte ratio (618 mg/kg bw/day) and the decreased Ca2+ level in females (294 mg/kg bw/day), which are regarded as being within normal physiological variation. Conclusion The study authors conclude that, since no test substance-related changes attributed to -arbutin were observed up to a dosage of 618 mg/kg bw/day (the maximum technically applicable dosage), this can be considered as the NOEL value. Ref.: 11 SCCS comment The change in the relative thymus weight (increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28-day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. SCCS conclusion on repeated dose toxicity A repeated dose 28-day oral study and 90-day dermal study with the rat only revealed some sporadic observations that could not be related to the test substance. Th","endpoint":"repeated dose toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"618","page":24,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 1000 | mg/kg bw/day | rat | oral | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=1000; DOSE=SCCS conclusion on repeated dose toxicity A repeated dose 28-day oral study and 90-day dermal study with the rat only revealed some sporadic observations that could not be related to the test substance.; EFFECT=(increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28-day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. SCCS conclusion on repeated dose toxicity A repeated dose 28-day oral study and 90-day dermal study with the rat only revealed some sporadic observations that could not be related to the test substance. Therefore in both tests, the highest dosage tested could be designated as NOEL, i.e. 1000 mg/kg bw/day for the repeated dose oral study and 618 mg/kg bw/day for the repeated dose dermal study. 3.3.5.3 Chronic ( 12 months) toxicity No data. 3.3.6 Mutagenicity / Genotoxicity Taken from SCCP/1158/08 (with minor modifications) 3.3.6.1 Mutagenicity/Genotoxicity in vitro Gene mutation test in bacteria Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA Replicates: Triplicates per test concentration Test substance: β-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"SCCS conclusion on repeated dose toxicity A repeated dose 28-day oral study and 90-day dermal study with the rat only revealed some sporadic observations that could not be related to the test substance.","duration":"28-day","effect":"(increase at lower dosage level and decrease at higher dosage levels) did not occur in the 28-day oral study, supporting the authors' finding that the observed variations were within the normal range of variation and not substance- related. SCCS conclusion on repeated dose toxicity A repeated dose 28-day oral study and 90-day dermal study with the rat only revealed some sporadic observations that could not be related to the test substance. Therefore in both tests, the highest dosage tested could be designated as NOEL, i.e. 1000 mg/kg bw/day for the repeated dose oral study and 618 mg/kg bw/day for the repeated dose dermal study. 3.3.5.3 Chronic ( 12 months) toxicity No data. 3.3.6 Mutagenicity / Genotoxicity Taken from SCCP/1158/08 (with minor modifications) 3.3.6.1 Mutagenicity/Genotoxicity in vitro Gene mutation test in bacteria Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium, TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA Replicates: Triplicates per test concentration Test substance: β-","endpoint":"repeated dose toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":24,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 400 | mg/kg bw/day | rat | - | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=400; DOSE=Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for -arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice.; EFFECT=spleen, calcification in brain thalamus, subcapsular hyperplasia in the adrenal gland, ovary cysts, cystic endometrial hyperplasia in the uterus and detachment or hypertrophy of articular chondrocytes in the joint. Tumour lesions included hepatocellular adenoma, bronchiolar/alveolar adenoma and malignant lymphoma. These lesions occurred in all groups (also in the control group). Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for -arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice. It is also concluded that the test substance is not carcinogenic under the conditions of the performed study. Ref.: 14 SCCS comment No rationale is given for the choice of another species than the one used in the 28-day or 90-day repeated dose study (mice instead of rats). In addition, the weight variation in the animals at the beginning of the study exceeded 20% ( 50%) and the intermediate haematological examin; CITATION=Ref.: 14 SCCS comment No rationale is given for the choice of another species than the one used in the 28-day or 90-day repeated dose study (mice instead of rats); CITATION_NUMBERS=[14,28,90]; REFERENCE=Ref.: 14 SCCS comment No rationale is given for the choice of another species than the one used in the 28-day or 90-day repeated dose study (mice instead of rats); DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 14 SCCS comment No rationale is given for the choice of another species than the one used in the 28-day or 90-day repeated dose study (mice instead of rats)","dose":"Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for -arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice.","duration":"28-day","effect":"spleen, calcification in brain thalamus, subcapsular hyperplasia in the adrenal gland, ovary cysts, cystic endometrial hyperplasia in the uterus and detachment or hypertrophy of articular chondrocytes in the joint. Tumour lesions included hepatocellular adenoma, bronchiolar/alveolar adenoma and malignant lymphoma. These lesions occurred in all groups (also in the control group). Conclusion The study authors conclude that, since the observed (non-)tumour lesions are the ones frequently observed in aging mice, the NOEL value for -arbutin in the present study is estimated to be 400 mg/kg bw/day in male and female mice. It is also concluded that the test substance is not carcinogenic under the conditions of the performed study. Ref.: 14 SCCS comment No rationale is given for the choice of another species than the one used in the 28-day or 90-day repeated dose study (mice instead of rats). In addition, the weight variation in the animals at the beginning of the study exceeded 20% ( 50%) and the intermediate haematological examin","endpoint":"repeated dose toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":27,"route":"","species":"rat","study_id":"sccs_o_169_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 1000 | mg/kg bw/day | rat | oral | 28-day | repeated dose toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=1000; DOSE=Systemic toxicity The acute oral toxicity profile of β-arbutin can be considered low, viewing the LD50-oral-rat value of 8715 mg/kg/day whereas the LD50-dermal-rat was >928 mg/kg (maximum practically applicable dosage).; EFFECT=arbutin and hydroquinone content (see below “Toxicokinetics”). Systemic toxicity The acute oral toxicity profile of β-arbutin can be considered low, viewing the LD50-oral-rat value of 8715 mg/kg/day whereas the LD50-dermal-rat was >928 mg/kg (maximum practically applicable dosage). A repeated dose 28-day oral study and 90-day dermal study with the rat only revealed some sporadic observations which could not be related to the test substance. Therefore in both tests, the highest dosage tested could be designated as NOEL, i.e. 1000 mg/kg bw/day for the repeated dose oral study and 618 mg/kg bw/day for the repeated dose dermal study. Toxicokinetics Hydrolysis to hydroquinone (HQ) has been described as significantly taking place in the case of oral intake of β-arbutin (stomach acids), but also to a lesser extent after dermal exposure [43, 38]. Subsequent enzymatic biotransformation (by phase II enzymes) of HQ may be expected in both cases [40, 42]. A human skin metabolism study revealed that daily topical application for 4 consecut; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"Systemic toxicity The acute oral toxicity profile of β-arbutin can be considered low, viewing the LD50-oral-rat value of 8715 mg/kg/day whereas the LD50-dermal-rat was >928 mg/kg (maximum practically applicable dosage).","duration":"28-day","effect":"arbutin and hydroquinone content (see below “Toxicokinetics”). Systemic toxicity The acute oral toxicity profile of β-arbutin can be considered low, viewing the LD50-oral-rat value of 8715 mg/kg/day whereas the LD50-dermal-rat was >928 mg/kg (maximum practically applicable dosage). A repeated dose 28-day oral study and 90-day dermal study with the rat only revealed some sporadic observations which could not be related to the test substance. Therefore in both tests, the highest dosage tested could be designated as NOEL, i.e. 1000 mg/kg bw/day for the repeated dose oral study and 618 mg/kg bw/day for the repeated dose dermal study. Toxicokinetics Hydrolysis to hydroquinone (HQ) has been described as significantly taking place in the case of oral intake of β-arbutin (stomach acids), but also to a lesser extent after dermal exposure [43, 38]. Subsequent enzymatic biotransformation (by phase II enzymes) of HQ may be expected in both cases [40, 42]. A human skin metabolism study revealed that daily topical application for 4 consecut","endpoint":"repeated dose toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":40,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_020"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 0.522 | µg/cm | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT=0.522; DOSE=LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.; EFFECT=SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Posi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","duration":"28d","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Posi","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"µg/cm","noael_value":"0.522","page":30,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =20 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 20; DOSE=LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.; EFFECT=SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) i; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","duration":"28d","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) i","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 20","page":30,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =74 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 74; DOSE=LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.; EFFECT=SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivoca; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","duration":"28d","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivoca","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 74","page":30,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =25 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 25; DOSE=LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.; EFFECT=SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage le; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","duration":"28d","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage le","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 25","page":30,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =75 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 75; DOSE=LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.; EFFECT=SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many year; CITATION=Ref.: 26, 29 Hydroquinone has been used for many year; CITATION_NUMBERS=[26,29]; REFERENCE=Ref.: 26, 29 Hydroquinone has been used for many year; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 26, 29 Hydroquinone has been used for many year","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","duration":"28d","effect":"SCCP/1158/08 Opinion on β-arbutin 30 3.3.12 Special investigations Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many year","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 75","page":30,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =15 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 15; DOSE=LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.; EFFECT=ns Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%. It does not directly bleach the skin,; CITATION=Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%; CITATION_NUMBERS=[26,29,2]; REFERENCE=Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%","dose":"LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin.","duration":"28d","effect":"ns Additional information on the impurity hydroquinone (1,4-Benzenediol): LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin. Absorption rate (5% aqueous solution)-human skin: 0.522 µg/cm²/h NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams). NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels ≥ 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%. It does not directly bleach the skin,","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 15","page":30,"route":"oral","species":"rat","study_id":"sccp_o_134_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | mg/kg bw/day | rat | dermal | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT=100; DOSE=Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin.; EFFECT=the presence of metabolic activation system in the presented in vitro mammalian chromosome aberration test. Therefore β-arbutin is considered to be non-mutagenic. Not all three tests as mentioned in the SCCP Notes of Guidance have been presented. Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin. Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day. Photo-induced adverse effects The presented summaries of a phototoxicity and photosensitisation assay with β-arbutin in the guinea pig conclude that the substance displays neither photototoxic nor photoallergic potential. The human repeated open application test with so-called "exposure to sunlight" lacks stan; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin.","duration":"","effect":"the presence of metabolic activation system in the presented in vitro mammalian chromosome aberration test. Therefore β-arbutin is considered to be non-mutagenic. Not all three tests as mentioned in the SCCP Notes of Guidance have been presented. Carcinogenicity A dermal carcinogenicity study in mice revealed that dosages up to 400 mg/kg bw/day failed to induce dose-related tumour formation due to the administration of β-arbutin. Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day. Photo-induced adverse effects The presented summaries of a phototoxicity and photosensitisation assay with β-arbutin in the guinea pig conclude that the substance displays neither photototoxic nor photoallergic potential. The human repeated open application test with so-called \"exposure to sunlight\" lacks stan","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":33,"route":"dermal","species":"rat","study_id":"sccp_o_134_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =150 | mg/kg/day | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_134; REPORT_TITLE=OPINION ON β-ARBUTIN; OPINION_NUMBER=SCCP/1158/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=15 April 2008; VALUE_TEXT== 150; DOSE=NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).; EFFECT=Unlabeled table on page 30: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","duration":"","effect":"Unlabeled table on page 30: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 150","page":30,"route":"","species":"rat","study_id":"sccp_o_134_noael_017"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 1550 | - | - | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=unclear:SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 29 Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; yet, subcutaneous injection is an uncommon application route in one-generation reproductive toxicity tests. 3.3.8.2 Teratogenicity No data submitted. 3.3.9 Toxicokinetics ß-Arbutin is hydrolysed into hydroquinone and glucose in the presence of weak acids. Cosmetics with ß-arbutin may contain small amounts of hydroquinone (HQ) as impurity. Hydrolysis of dermally applied arbutin may also occur to some extent on the skin surface (by microflora) and in the skin (by hydrolases). Data on skin metab; EFFECT=SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 29 Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; yet, subcutaneous injection is an uncommon application route in one-generation reproductive toxicity tests. 3.3.8.2 Teratogenicity No data submitted. 3.3.9 Toxicokinetics ß-Arbutin is hydrolysed into hydroquinone and glucose in the presence of weak acids. Cosmetics with ß-arbutin may contain small amounts of hydroquinone (HQ) as impurity. Hydrolysis of dermally applied arbutin may also occur to some extent on the skin surface (by microflora) and in the skin (by hydrolases). Data on skin metab; CITATION=Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; CITATION_NUMBERS=[15]; REFERENCE=Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin","dose":"","duration":"","effect":"SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 29 Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; yet, subcutaneous injection is an uncommon application route in one-generation reproductive toxicity tests. 3.3.8.2 Teratogenicity No data submitted. 3.3.9 Toxicokinetics ß-Arbutin is hydrolysed into hydroquinone and glucose in the presence of weak acids. Cosmetics with ß-arbutin may contain small amounts of hydroquinone (HQ) as impurity. Hydrolysis of dermally applied arbutin may also occur to some extent on the skin surface (by microflora) and in the skin (by hydrolases). Data on skin metab","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1550/15 Opinion on β-arbutin ________________________________________________________________________________________ 29 Ref.: 15 SCCS comment This is the lowest NOEL for -arbutin; yet, subcutaneous injection is an uncommon application route in one-generation reproductive toxicity tests. 3.3.8.2 Teratogenicity No data submitted. 3.3.9 Toxicokinetics ß-Arbutin is hydrolysed into hydroquinone and glucose in the presence of weak acids. Cosmetics with ß-arbutin may contain small amounts of hydroquinone (HQ) as impurity. Hydrolysis of dermally applied arbutin may also occur to some extent on the skin surface (by microflora) and in the skin (by hydrolases). Data on skin metab","page":29,"route":"","species":"","study_id":"sccs_o_169_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =20 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 20; DOSE=3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...; EFFECT=tin inhibits melanin production in guinea pig B16 cells and decreases tyrosinase activity in a cell-free system (Lim et al. 2005). Using A375 human malignant melanoma cells in a proteomic approach, ß-arbutin was shown to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Posit; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...","duration":"28d","effect":"tin inhibits melanin production in guinea pig B16 cells and decreases tyrosinase activity in a cell-free system (Lim et al. 2005). Using A375 human malignant melanoma cells in a proteomic approach, ß-arbutin was shown to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Posit","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 20","page":35,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =20 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 20; DOSE=3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...; EFFECT=ea pig B16 cells and decreases tyrosinase activity in a cell-free system (Lim et al. 2005). Using A375 human malignant melanoma cells in a proteomic approach, ß-arbutin was shown to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...","duration":"28d","effect":"ea pig B16 cells and decreases tyrosinase activity in a cell-free system (Lim et al. 2005). Using A375 human malignant melanoma cells in a proteomic approach, ß-arbutin was shown to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 20","page":35,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =74 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 74; DOSE=3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...; EFFECT=activity in a cell-free system (Lim et al. 2005). Using A375 human malignant melanoma cells in a proteomic approach, ß-arbutin was shown to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...","duration":"28d","effect":"activity in a cell-free system (Lim et al. 2005). Using A375 human malignant melanoma cells in a proteomic approach, ß-arbutin was shown to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 74","page":35,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =25 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 25; DOSE=3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...; EFFECT=5 human malignant melanoma cells in a proteomic approach, ß-arbutin was shown to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage le; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...","duration":"28d","effect":"5 human malignant melanoma cells in a proteomic approach, ß-arbutin was shown to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage le","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 25","page":35,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =75 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 75; DOSE=3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...; EFFECT=wn to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many year; CITATION=Ref.: 26, 29 Hydroquinone has been used for many year; CITATION_NUMBERS=[26,29]; REFERENCE=Ref.: 26, 29 Hydroquinone has been used for many year; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 26, 29 Hydroquinone has been used for many year","dose":"3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...","duration":"28d","effect":"wn to have a role in tumour suppression, as found by regulation of p53 and cell apoptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many year","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 75","page":35,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =15 | mg/kg/day | rat | oral | 28d | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 15; DOSE=3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...; EFFECT=poptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%. It does not directly bleach the skin,; CITATION=Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%; CITATION_NUMBERS=[26,29,2]; REFERENCE=Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%; DETAILS_JSON={"cas_number":"497-76-7","citation":"Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%","dose":"3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental...","duration":"28d","effect":"poptosis (Nawarak et al. 2005). 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated LD50-oral-rat = 298 mg/kg Slightly irritating to the eye Sensitising to the skin NOEL (28d/90d-oral-rat) = 20 mg/kg/day NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams) NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects). NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity). NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity). Negative in the Ames test, the dominant lethal assay and the mouse spot test. Positive in the in vitro chromosome aberration test (+S9) Positive (i.p.) and weakly positive (oral) in the in vivo micronucleus test. Equivocal conclusions on potential carcinogenic effects at dosage levels 25 mg/kg/day. Ref.: 26, 29 Hydroquinone has been used for many years in skin-bleaching preparations up to 2%. It does not directly bleach the skin,","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 15","page":35,"route":"oral","species":"rat","study_id":"sccs_o_169_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | mg/kg bw/day | rat | - | 12 months | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT=100; DOSE=Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day.; EFFECT=in the animals at the beginning of the study exceeded 20% (50%) and the intermediate haematological examination (after 12 months) was not performed. Finally, the non-tumour and the tumour lesions observed in all animals (including the control group) reveal that, whether or not caused by aging alone, the general condition of the animals appeared to be poor. No conclusion with regard to carcinogenicity can be drawn from this study. Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day. Photo-induced adverse effects The presented summaries of a phototoxicity and photosensitisation assay with β-arbutin in the guinea pig conclude that the substance displays neither phototoxic nor photoallergic potential. The human repeated open application test with so-called "exposure to sunlight" lacks standa; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day.","duration":"12 months","effect":"in the animals at the beginning of the study exceeded 20% (50%) and the intermediate haematological examination (after 12 months) was not performed. Finally, the non-tumour and the tumour lesions observed in all animals (including the control group) reveal that, whether or not caused by aging alone, the general condition of the animals appeared to be poor. No conclusion with regard to carcinogenicity can be drawn from this study. Reproductive toxicity A one-generation reproduction study with β-arbutin revealed a NOEL for reproduction toxicity of 100 mg/kg bw/day based upon the observation of body weight decrease in female foetuses and decreased organ weights of the unilateral ovary of female F1 rats at 400 mg/kg bw/day. Photo-induced adverse effects The presented summaries of a phototoxicity and photosensitisation assay with β-arbutin in the guinea pig conclude that the substance displays neither phototoxic nor photoallergic potential. The human repeated open application test with so-called \"exposure to sunlight\" lacks standa","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":41,"route":"","species":"rat","study_id":"sccs_o_169_noael_021"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | =150 | mg/kg/day | rat | - | - | reproductive toxicity | SOURCE_SUBDIR=sccs_o_169; REPORT_TITLE=OPINION ON β-arbutin; OPINION_NUMBER=SCCS/1550/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 March 2015; VALUE_TEXT== 150; DOSE=NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).; EFFECT=Unlabeled table on page 35: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"497-76-7","citation":"","dose":"NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","duration":"","effect":"Unlabeled table on page 35: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","endpoint":"reproductive toxicity","ingredient":"Beta-Arbutin","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 150","page":35,"route":"","species":"rat","study_id":"sccs_o_169_noael_027"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | C5INA23HXF | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C12H16O7","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"C5INA23HXF"} |
| openFDA substances | FDA UNII substance identifier | C5INA23HXF | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C12H16O7","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"C5INA23HXF"} |
| openFDA substances | FDA UNII substance identifier | C5INA23HXF | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C12H16O7","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"C5INA23HXF"} |
| openFDA substances | FDA UNII substance identifier | C5INA23HXF | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C12H16O7","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"C5INA23HXF"} |