Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal, THPuric acid (4-(Tetrahydropyranyloxy)phenol)

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 15; DOSE=NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).; EFFECT=Unlabeled table on page 38: NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).","duration":"","effect":"Unlabeled table on page 38: NOEL (1-generation reproduction toxicity-rat) = 15 mg/kg/day (general toxicity).","endpoint":"","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 15","page":38,"route":"","species":"rat","study_id":"sccs_o_183_noael_026"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 20; DOSE=NOEL (28d/90d-oral-rat) = 20 mg/kg/day; EFFECT=Unlabeled table on page 38: NOEL (28d/90d-oral-rat) = 20 mg/kg/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"NOEL (28d/90d-oral-rat) = 20 mg/kg/day","duration":"28d","effect":"Unlabeled table on page 38: NOEL (28d/90d-oral-rat) = 20 mg/kg/day","endpoint":"","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 20","page":38,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_022"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 74; DOSE=NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day; EFFECT=Unlabeled table on page 38: NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day","duration":"28d","effect":"Unlabeled table on page 38: NOAEL (28d/90d-dermal-rat) = 74 mg/kg/day","endpoint":"","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 74","page":38,"route":"dermal","species":"rat","study_id":"sccs_o_183_noael_023"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=316; DOSE=dication of any neurological impairment at any dose level in any of the treated animals.; EFFECT=dication of any neurological impairment at any dose level in any of the treated animals. Conclusion Deoxyarbutin was tolerated without mortality up to the high dose level of 1000 mg/kg bw. Slight signs of systemic toxicity occurred only at 1000 mg/kg bw in male and female rats but no specific mode of action or target organ was identified. There were no gross or histopathological findings and no impairment of any parameter in the comprehensive functional observation battery. Thus, the study authors stated that the no observed adverse effect level (NOAEL) was 316 mg/kg bw for male and female F344 rats under the conditions of this study. Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin Batch: HT0059.01-04 Purity: 99% Dose levels: 3% deoxyarbutin in a cream formulation Control: Vehicle cream formulation Dose volume: 2 ml/kg bw Route: Dermal (open, intact skin) Exposure period: 28 days Exposure frequency: once daily for 6 h,; CITATION=Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin; CITATION_NUMBERS=[18,28,5]; REFERENCE=Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin; DETAILS_JSON={"cas_number":"53936-56-4","citation":"Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin","dose":"dication of any neurological impairment at any dose level in any of the treated animals.","duration":"28 day","effect":"dication of any neurological impairment at any dose level in any of the treated animals. Conclusion Deoxyarbutin was tolerated without mortality up to the high dose level of 1000 mg/kg bw. Slight signs of systemic toxicity occurred only at 1000 mg/kg bw in male and female rats but no specific mode of action or target organ was identified. There were no gross or histopathological findings and no impairment of any parameter in the comprehensive functional observation battery. Thus, the study authors stated that the no observed adverse effect level (NOAEL) was 316 mg/kg bw for male and female F344 rats under the conditions of this study. Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin Batch: HT0059.01-04 Purity: 99% Dose levels: 3% deoxyarbutin in a cream formulation Control: Vehicle cream formulation Dose volume: 2 ml/kg bw Route: Dermal (open, intact skin) Exposure period: 28 days Exposure frequency: once daily for 6 h,","endpoint":"","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw","noael_value":"316","page":23,"route":"dermal","species":"rat","study_id":"sccs_o_183_noael_001"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=316; DOSE=rment at any dose level in any of the treated animals.; EFFECT=rment at any dose level in any of the treated animals. Conclusion Deoxyarbutin was tolerated without mortality up to the high dose level of 1000 mg/kg bw. Slight signs of systemic toxicity occurred only at 1000 mg/kg bw in male and female rats but no specific mode of action or target organ was identified. There were no gross or histopathological findings and no impairment of any parameter in the comprehensive functional observation battery. Thus, the study authors stated that the no observed adverse effect level (NOAEL) was 316 mg/kg bw for male and female F344 rats under the conditions of this study. Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin Batch: HT0059.01-04 Purity: 99% Dose levels: 3% deoxyarbutin in a cream formulation Control: Vehicle cream formulation Dose volume: 2 ml/kg bw Route: Dermal (open, intact skin) Exposure period: 28 days Exposure frequency: once daily for 6 h, 7days/w; CITATION=Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin; CITATION_NUMBERS=[18,28,5]; REFERENCE=Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin; DETAILS_JSON={"cas_number":"53936-56-4","citation":"Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin","dose":"rment at any dose level in any of the treated animals.","duration":"28 day","effect":"rment at any dose level in any of the treated animals. Conclusion Deoxyarbutin was tolerated without mortality up to the high dose level of 1000 mg/kg bw. Slight signs of systemic toxicity occurred only at 1000 mg/kg bw in male and female rats but no specific mode of action or target organ was identified. There were no gross or histopathological findings and no impairment of any parameter in the comprehensive functional observation battery. Thus, the study authors stated that the no observed adverse effect level (NOAEL) was 316 mg/kg bw for male and female F344 rats under the conditions of this study. Ref: 18 28 day dermal toxicity study in the rabbit Guideline/method: / Species/strain: Rabbit/New Zealand White Group size: 5 males and 5 females per group Test substance: deoxyarbutin Batch: HT0059.01-04 Purity: 99% Dose levels: 3% deoxyarbutin in a cream formulation Control: Vehicle cream formulation Dose volume: 2 ml/kg bw Route: Dermal (open, intact skin) Exposure period: 28 days Exposure frequency: once daily for 6 h, 7days/w","endpoint":"","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw","noael_value":"316","page":23,"route":"dermal","species":"rat","study_id":"sccs_o_183_noael_002"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=316; DOSE=NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS:; EFFECT=ose. 90-day dermal rabbit toxicity study for deoxyarbutin: NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS: 800 / 0.77 = 1039 NOTE: An additional MOS calculation - based on the systemic exposure dose (SED) for deoxyarbutin using the mean+2 SD, i.e. 80.04% or 134 µg/cm2 from the in vitro dermal penetration study (ref. 27) and the NOAEL of 316 mg/kg bw from the 28-day oral toxicity study in rats (ref. 18) - arrives also at a sufficient margin of safety (of 250). The oral NOAEL is considered as worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity. Safety evaluation for the Hydroquinone (HQ) formed Other than alpha- or beta-arbutin (SCCS/1550/2015 and SCCS 1552/2015) where partial hydrolysis of the absorbed fraction can occur within the skin, the dermally absorbed deoxyarbutin undergoes apparently extensive phase-II metabolism with no measurable release of hydroquinone in skin. Ho; CITATION=(ref. 27); CITATION_NUMBERS=[27]; REFERENCE=(ref. 27); DETAILS_JSON={"cas_number":"53936-56-4","citation":"(ref. 27)","dose":"NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS:","duration":"90-day","effect":"ose. 90-day dermal rabbit toxicity study for deoxyarbutin: NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS: 800 / 0.77 = 1039 NOTE: An additional MOS calculation - based on the systemic exposure dose (SED) for deoxyarbutin using the mean+2 SD, i.e. 80.04% or 134 µg/cm2 from the in vitro dermal penetration study (ref. 27) and the NOAEL of 316 mg/kg bw from the 28-day oral toxicity study in rats (ref. 18) - arrives also at a sufficient margin of safety (of 250). The oral NOAEL is considered as worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity. Safety evaluation for the Hydroquinone (HQ) formed Other than alpha- or beta-arbutin (SCCS/1550/2015 and SCCS 1552/2015) where partial hydrolysis of the absorbed fraction can occur within the skin, the dermally absorbed deoxyarbutin undergoes apparently extensive phase-II metabolism with no measurable release of hydroquinone in skin. Ho","endpoint":"","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw","noael_value":"316","page":40,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_014"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 25; DOSE=NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams); EFFECT=Unlabeled table on page 38: NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams)","duration":"developmental","effect":"Unlabeled table on page 38: NOEL (developmental toxicity-rabbit) = 25 mg/kg/day (dams)","endpoint":"developmental toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 25","page":38,"route":"","species":"rabbit","study_id":"sccs_o_183_noael_024"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 75; DOSE=NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).; EFFECT=Unlabeled table on page 38: NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).","duration":"developmental","effect":"Unlabeled table on page 38: NOEL (developmental toxicity-rabbit) = 75 mg/kg/day (teratogenic effects).","endpoint":"developmental toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 75","page":38,"route":"","species":"rabbit","study_id":"sccs_o_183_noael_025"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=0.0218; DOSE=Q) from application of deoxyarbutin containing cosmetic products is assessed below and compared to risks related to a) repeated dose toxicity, b) induction of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with h...; EFFECT=Q) from application of deoxyarbutin containing cosmetic products is assessed below and compared to risks related to a) repeated dose toxicity, b) induction of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat): 20 mg/kg bw/day NOAEL (1-generation reprotox - rat) 15 mg/kg bw/day SED for HQ: 0.0218 mg/kg bw/day  MOS (NOAEL/SED) values would be 917 (90 day) or 688 (reprotox) b) HQ induction of ochronosis HQ is also suspected to cause exogenous ochronosis (EO). As a NOAEL has not been established for exogenous ochronosis, 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; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"Q) from application of deoxyarbutin containing cosmetic products is assessed below and compared to risks related to a) repeated dose toxicity, b) induction of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with h...","duration":"chronic","effect":"Q) from application of deoxyarbutin containing cosmetic products is assessed below and compared to risks related to a) repeated dose toxicity, b) induction of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat): 20 mg/kg bw/day NOAEL (1-generation reprotox - rat) 15 mg/kg bw/day SED for HQ: 0.0218 mg/kg bw/day  MOS (NOAEL/SED) values would be 917 (90 day) or 688 (reprotox) b) HQ induction of ochronosis HQ is also suspected to cause exogenous ochronosis (EO). As a NOAEL has not been established for exogenous ochronosis, 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","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"0.0218","page":41,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_017"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=0.0218; DOSE=tion of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat):; EFFECT=tion of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat): 20 mg/kg bw/day NOAEL (1-generation reprotox - rat) 15 mg/kg bw/day SED for HQ: 0.0218 mg/kg bw/day  MOS (NOAEL/SED) values would be 917 (90 day) or 688 (reprotox) b) HQ induction of ochronosis HQ is also suspected to cause exogenous ochronosis (EO). As a NOAEL has not been established for exogenous ochronosis, 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 HQ-induced ochronosis: 1 % Maximum quantity of a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"tion of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat):","duration":"chronic","effect":"tion of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat): 20 mg/kg bw/day NOAEL (1-generation reprotox - rat) 15 mg/kg bw/day SED for HQ: 0.0218 mg/kg bw/day  MOS (NOAEL/SED) values would be 917 (90 day) or 688 (reprotox) b) HQ induction of ochronosis HQ is also suspected to cause exogenous ochronosis (EO). As a NOAEL has not been established for exogenous ochronosis, 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 HQ-induced ochronosis: 1 % Maximum quantity of a","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"0.0218","page":41,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_018"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 0.77; DOSE=3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for deoxyarbutin (3% in face cream, applied once per day) Application of face cream (1.54 g/day, according to the SCCS NoG, Table 3) with 3% a.i. equals 46.2 mg deoxyarbutin/person/day; adjusted to 60 kg b.w. = 0.77 mg/kg x day.; EFFECT=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 deoxyarbutin (3% in face cream, applied once per day) Application of face cream (1.54 g/day, according to the SCCS NoG, Table 3) with 3% a.i. equals 46.2 mg deoxyarbutin/person/day; adjusted to 60 kg b.w. = 0.77 mg/kg x day. For calculation of a margin of safety, the NOAEL of a subchronic dermal study (ref. 40) is divided by the human external dose. 90-day dermal rabbit toxicity study for deoxyarbutin: NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS: 800 / 0.77 = 1039 NOTE: An additional MOS calculation - based on the systemic exposure dose (SED) for deoxyarbutin using the mean+2 SD, i.e. 80.04% or 134 µg/cm2 from the in vitro dermal penetration study (ref. 27) and the NOAEL of 316 mg/kg bw from the 28-day oral toxicity study in rats (re; CITATION=(ref. 40); CITATION_NUMBERS=[40]; REFERENCE=(ref. 40); DETAILS_JSON={"cas_number":"53936-56-4","citation":"(ref. 40)","dose":"3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for deoxyarbutin (3% in face cream, applied once per day) Application of face cream (1.54 g/day, according to the SCCS NoG, Table 3) with 3% a.i. equals 46.2 mg deoxyarbutin/person/day; adjusted to 60 kg b.w. = 0.77 mg/kg x day.","duration":"subchronic","effect":"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 deoxyarbutin (3% in face cream, applied once per day) Application of face cream (1.54 g/day, according to the SCCS NoG, Table 3) with 3% a.i. equals 46.2 mg deoxyarbutin/person/day; adjusted to 60 kg b.w. = 0.77 mg/kg x day. For calculation of a margin of safety, the NOAEL of a subchronic dermal study (ref. 40) is divided by the human external dose. 90-day dermal rabbit toxicity study for deoxyarbutin: NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS: 800 / 0.77 = 1039 NOTE: An additional MOS calculation - based on the systemic exposure dose (SED) for deoxyarbutin using the mean+2 SD, i.e. 80.04% or 134 µg/cm2 from the in vitro dermal penetration study (ref. 27) and the NOAEL of 316 mg/kg bw from the 28-day oral toxicity study in rats (re","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg","noael_value":"= 0.77","page":40,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_011"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 0.77; DOSE=3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for deoxyarbutin (3% in face cream, applied once per day) Application of face cream (1.54 g/day, according to the SCCS NoG, Table 3) with 3% a.i. equals 46.2 mg deoxyarbutin/person/day; adjusted to 60 kg b.w. = 0.77 mg/kg x day.; EFFECT=ption for HQ. 3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for deoxyarbutin (3% in face cream, applied once per day) Application of face cream (1.54 g/day, according to the SCCS NoG, Table 3) with 3% a.i. equals 46.2 mg deoxyarbutin/person/day; adjusted to 60 kg b.w. = 0.77 mg/kg x day. For calculation of a margin of safety, the NOAEL of a subchronic dermal study (ref. 40) is divided by the human external dose. 90-day dermal rabbit toxicity study for deoxyarbutin: NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS: 800 / 0.77 = 1039 NOTE: An additional MOS calculation - based on the systemic exposure dose (SED) for deoxyarbutin using the mean+2 SD, i.e. 80.04% or 134 µg/cm2 from the in vitro dermal penetration study (ref. 27) and the NOAEL of 316 mg/kg bw from the 28-day oral toxicity study in rats (ref. 18) - arrives also at a sufficient margin of safety (of 250). The oral NOAEL is considered as worst-case scenario for deoxyarbutin since; CITATION=(ref. 40); CITATION_NUMBERS=[40]; REFERENCE=(ref. 40); DETAILS_JSON={"cas_number":"53936-56-4","citation":"(ref. 40)","dose":"3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for deoxyarbutin (3% in face cream, applied once per day) Application of face cream (1.54 g/day, according to the SCCS NoG, Table 3) with 3% a.i. equals 46.2 mg deoxyarbutin/person/day; adjusted to 60 kg b.w. = 0.77 mg/kg x day.","duration":"subchronic","effect":"ption for HQ. 3.3.14 Safety evaluation (including calculation of the Margin of Safety) Safety evaluation for deoxyarbutin (3% in face cream, applied once per day) Application of face cream (1.54 g/day, according to the SCCS NoG, Table 3) with 3% a.i. equals 46.2 mg deoxyarbutin/person/day; adjusted to 60 kg b.w. = 0.77 mg/kg x day. For calculation of a margin of safety, the NOAEL of a subchronic dermal study (ref. 40) is divided by the human external dose. 90-day dermal rabbit toxicity study for deoxyarbutin: NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS: 800 / 0.77 = 1039 NOTE: An additional MOS calculation - based on the systemic exposure dose (SED) for deoxyarbutin using the mean+2 SD, i.e. 80.04% or 134 µg/cm2 from the in vitro dermal penetration study (ref. 27) and the NOAEL of 316 mg/kg bw from the 28-day oral toxicity study in rats (ref. 18) - arrives also at a sufficient margin of safety (of 250). The oral NOAEL is considered as worst-case scenario for deoxyarbutin since","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg","noael_value":"= 0.77","page":40,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_012"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=3; DOSE=Repeated dermal application of deoxyarbutin in rabbits either as 3% cream formulation for 28 days or as 1, 5 and 40% propylene glycol/ethanol solution for 91 days did not lead to any substance-related systemic findings up to the highest dose level investigated.; EFFECT=nsidered as the worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity. Also in light of the pronounced route effect observed in the in vivo genotoxicity tests (see 3.3.6.), the SCCS concluded that the oral application route should be considered as inappropriate for investigating safety of desoxyarbutin in the context of its dermal application, and therefore chose the subchronic dermal toxicity study to derive a NOAEL for the calculation of a margin of safety. Repeated dermal application of deoxyarbutin in rabbits either as 3% cream formulation for 28 days or as 1, 5 and 40% propylene glycol/ethanol solution for 91 days did not lead to any substance-related systemic findings up to the highest dose level investigated. The respective NOAEL for systemic toxicity in rabbits was 40% deoxyarbutin corresponding to about 800 mg/kg bw. This value will be used for risk assessment and the calculation of the margin of safety (MoS). Mutage; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"Repeated dermal application of deoxyarbutin in rabbits either as 3% cream formulation for 28 days or as 1, 5 and 40% propylene glycol/ethanol solution for 91 days did not lead to any substance-related systemic findings up to the highest dose level investigated.","duration":"subchronic","effect":"nsidered as the worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity. Also in light of the pronounced route effect observed in the in vivo genotoxicity tests (see 3.3.6.), the SCCS concluded that the oral application route should be considered as inappropriate for investigating safety of desoxyarbutin in the context of its dermal application, and therefore chose the subchronic dermal toxicity study to derive a NOAEL for the calculation of a margin of safety. Repeated dermal application of deoxyarbutin in rabbits either as 3% cream formulation for 28 days or as 1, 5 and 40% propylene glycol/ethanol solution for 91 days did not lead to any substance-related systemic findings up to the highest dose level investigated. The respective NOAEL for systemic toxicity in rabbits was 40% deoxyarbutin corresponding to about 800 mg/kg bw. This value will be used for risk assessment and the calculation of the margin of safety (MoS). Mutage","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"%","noael_value":"3","page":43,"route":"oral","species":"rabbit","study_id":"sccs_o_183_noael_020"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=20; DOSE=uld result in internal HQ dose of 1.31 mg/day and (:; EFFECT=uld result in internal HQ dose of 1.31 mg/day and (: 60 kg) SED for HQ of 0.0281 mg/kg bw/day. The estimated exposure to hydroquinone (HQ) from application of deoxyarbutin containing cosmetic products is assessed below and compared to risks related to a) repeated dose toxicity, b) induction of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat): 20 mg/kg bw/day NOAEL (1-generation reprotox - rat) 15 mg/kg bw/day SED for HQ: 0.0218 mg/kg bw/day  MOS (NOAEL/SED) values would be 917 (90 day) or 688 (reprotox) b) HQ induction of ochronosis HQ is also suspected to cause exogenous ochronosis (EO). As a NOAEL has not been established for exogenous ochronosis, 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; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"uld result in internal HQ dose of 1.31 mg/day and (:","duration":"chronic","effect":"uld result in internal HQ dose of 1.31 mg/day and (: 60 kg) SED for HQ of 0.0281 mg/kg bw/day. The estimated exposure to hydroquinone (HQ) from application of deoxyarbutin containing cosmetic products is assessed below and compared to risks related to a) repeated dose toxicity, b) induction of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat): 20 mg/kg bw/day NOAEL (1-generation reprotox - rat) 15 mg/kg bw/day SED for HQ: 0.0218 mg/kg bw/day  MOS (NOAEL/SED) values would be 917 (90 day) or 688 (reprotox) b) HQ induction of ochronosis HQ is also suspected to cause exogenous ochronosis (EO). As a NOAEL has not been established for exogenous ochronosis, 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","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":41,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_015"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=20; DOSE=60 kg) SED for HQ of 0.0281 mg/kg bw/day.; EFFECT=and (: 60 kg) SED for HQ of 0.0281 mg/kg bw/day. The estimated exposure to hydroquinone (HQ) from application of deoxyarbutin containing cosmetic products is assessed below and compared to risks related to a) repeated dose toxicity, b) induction of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat): 20 mg/kg bw/day NOAEL (1-generation reprotox - rat) 15 mg/kg bw/day SED for HQ: 0.0218 mg/kg bw/day  MOS (NOAEL/SED) values would be 917 (90 day) or 688 (reprotox) b) HQ induction of ochronosis HQ is also suspected to cause exogenous ochronosis (EO). As a NOAEL has not been established for exogenous ochronosis, 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; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"60 kg) SED for HQ of 0.0281 mg/kg bw/day.","duration":"chronic","effect":"and (: 60 kg) SED for HQ of 0.0281 mg/kg bw/day. The estimated exposure to hydroquinone (HQ) from application of deoxyarbutin containing cosmetic products is assessed below and compared to risks related to a) repeated dose toxicity, b) induction of ochronosis, and c) carcinogenicity. a) HQ repeated dose toxicity In this part of the safety assessment, MOS values are calculated from literature data on sub/-chronic toxicity tests with hydroquinone (see section 3.3.13) NOAEL (90 day oral - rat): 20 mg/kg bw/day NOAEL (1-generation reprotox - rat) 15 mg/kg bw/day SED for HQ: 0.0218 mg/kg bw/day  MOS (NOAEL/SED) values would be 917 (90 day) or 688 (reprotox) b) HQ induction of ochronosis HQ is also suspected to cause exogenous ochronosis (EO). As a NOAEL has not been established for exogenous ochronosis, 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","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":41,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_016"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=40; DOSE=Repeated dermal application of deoxyarbutin in rabbits either as 3% cream formulation for 28 days or as 1, 5 and 40% propylene glycol/ethanol solution for 91 days did not lead to any substance-related systemic findings up to the highest dose level investigated.; EFFECT=te should be considered as inappropriate for investigating safety of desoxyarbutin in the context of its dermal application, and therefore chose the subchronic dermal toxicity study to derive a NOAEL for the calculation of a margin of safety. Repeated dermal application of deoxyarbutin in rabbits either as 3% cream formulation for 28 days or as 1, 5 and 40% propylene glycol/ethanol solution for 91 days did not lead to any substance-related systemic findings up to the highest dose level investigated. The respective NOAEL for systemic toxicity in rabbits was 40% deoxyarbutin corresponding to about 800 mg/kg bw. This value will be used for risk assessment and the calculation of the margin of safety (MoS). Mutagenicity/Genotoxicity Overall, the genotoxicity of deoxyarbutin is sufficiently investigated in valid genotoxicity tests for the 3 endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Deoxyarbutin did not induce gene mutations in bacteria. In human lymphocytes deoxyarbutin showed a clastogenic pote; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"Repeated dermal application of deoxyarbutin in rabbits either as 3% cream formulation for 28 days or as 1, 5 and 40% propylene glycol/ethanol solution for 91 days did not lead to any substance-related systemic findings up to the highest dose level investigated.","duration":"subchronic","effect":"te should be considered as inappropriate for investigating safety of desoxyarbutin in the context of its dermal application, and therefore chose the subchronic dermal toxicity study to derive a NOAEL for the calculation of a margin of safety. Repeated dermal application of deoxyarbutin in rabbits either as 3% cream formulation for 28 days or as 1, 5 and 40% propylene glycol/ethanol solution for 91 days did not lead to any substance-related systemic findings up to the highest dose level investigated. The respective NOAEL for systemic toxicity in rabbits was 40% deoxyarbutin corresponding to about 800 mg/kg bw. This value will be used for risk assessment and the calculation of the margin of safety (MoS). Mutagenicity/Genotoxicity Overall, the genotoxicity of deoxyarbutin is sufficiently investigated in valid genotoxicity tests for the 3 endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Deoxyarbutin did not induce gene mutations in bacteria. In human lymphocytes deoxyarbutin showed a clastogenic pote","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"%","noael_value":"40","page":43,"route":"dermal","species":"rabbit","study_id":"sccs_o_183_noael_021"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=316; DOSE=The functional observation battery revealed no indication of any neurological impairment at any dose level.; EFFECT=eased, but without any histopathological correlates. The functional observation battery revealed no indication of any neurological impairment at any dose level. Clear or severe organ toxicity was not observed morphologically even at the limit dose of 1000 mg/kg bw. Oral dosing may be considered as worst-case scenario for deoxyarbutin since it is likely that the acidic stomach environment led to the formation of a (non-quantifiable) portion of hydroquinone, causing the observed effects. The No-Adverse-Effect-Level (NOAEL) for subacute toxicity after 28-day oral treatment was 316 mg/kg bw in male and female rats. This value may be considered as the worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"The functional observation battery revealed no indication of any neurological impairment at any dose level.","duration":"subacute","effect":"eased, but without any histopathological correlates. The functional observation battery revealed no indication of any neurological impairment at any dose level. Clear or severe organ toxicity was not observed morphologically even at the limit dose of 1000 mg/kg bw. Oral dosing may be considered as worst-case scenario for deoxyarbutin since it is likely that the acidic stomach environment led to the formation of a (non-quantifiable) portion of hydroquinone, causing the observed effects. The No-Adverse-Effect-Level (NOAEL) for subacute toxicity after 28-day oral treatment was 316 mg/kg bw in male and female rats. This value may be considered as the worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity.","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw","noael_value":"316","page":25,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_003"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=316; DOSE=40) is divided by the human external dose.; EFFECT== 0.77 mg/kg x day. For calculation of a margin of safety, the NOAEL of a subchronic dermal study (ref. 40) is divided by the human external dose. 90-day dermal rabbit toxicity study for deoxyarbutin: NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS: 800 / 0.77 = 1039 NOTE: An additional MOS calculation - based on the systemic exposure dose (SED) for deoxyarbutin using the mean+2 SD, i.e. 80.04% or 134 µg/cm2 from the in vitro dermal penetration study (ref. 27) and the NOAEL of 316 mg/kg bw from the 28-day oral toxicity study in rats (ref. 18) - arrives also at a sufficient margin of safety (of 250). The oral NOAEL is considered as worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity. Safety evaluation for the Hydroquinone (HQ) formed Other than alpha- or beta-arbutin (SCCS/1550/2015 and SCCS 1552/2015) where partial hydrolysis of the absorbed fraction can occur within the ski; CITATION=(ref. 40); CITATION_NUMBERS=[40]; REFERENCE=(ref. 40); DETAILS_JSON={"cas_number":"53936-56-4","citation":"(ref. 40)","dose":"40) is divided by the human external dose.","duration":"subchronic","effect":"= 0.77 mg/kg x day. For calculation of a margin of safety, the NOAEL of a subchronic dermal study (ref. 40) is divided by the human external dose. 90-day dermal rabbit toxicity study for deoxyarbutin: NOAEL for systemic toxicity (mg/kg bw) about 800 Human external dose (mg/kg bw) 0.77 MOS: 800 / 0.77 = 1039 NOTE: An additional MOS calculation - based on the systemic exposure dose (SED) for deoxyarbutin using the mean+2 SD, i.e. 80.04% or 134 µg/cm2 from the in vitro dermal penetration study (ref. 27) and the NOAEL of 316 mg/kg bw from the 28-day oral toxicity study in rats (ref. 18) - arrives also at a sufficient margin of safety (of 250). The oral NOAEL is considered as worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity. Safety evaluation for the Hydroquinone (HQ) formed Other than alpha- or beta-arbutin (SCCS/1550/2015 and SCCS 1552/2015) where partial hydrolysis of the absorbed fraction can occur within the ski","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw","noael_value":"316","page":40,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_013"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=316; DOSE=e level of 1000 mg/kg bw consisting of transient clinical findings, slightly reduced food consumption and retarded bodyweight gain, minor haematological effects in females and slight impairment of single clinical chemistry parameters.; EFFECT=e level of 1000 mg/kg bw consisting of transient clinical findings, slightly reduced food consumption and retarded bodyweight gain, minor haematological effects in females and slight impairment of single clinical chemistry parameters. The relative liver weights of both sexes and the relative kidney weights of the males were increased but without any histopathological correlation. The functional observation battery revealed no indication of any neurological impairment at any dose level. The No-Adverse-Effect-Level (NOAEL) for subacute toxicity in rats after 28-day oral treatment was 316 mg/kg bw. This value may be considered as the worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity. Also in light of the pronounced route effect observed in the in vivo genotoxicity tests (see 3.3.6.), the SCCS concluded that the oral application route should be considered as inappropriate for investigating safety of desoxyarbutin in the contex; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"e level of 1000 mg/kg bw consisting of transient clinical findings, slightly reduced food consumption and retarded bodyweight gain, minor haematological effects in females and slight impairment of single clinical chemistry parameters.","duration":"subacute","effect":"e level of 1000 mg/kg bw consisting of transient clinical findings, slightly reduced food consumption and retarded bodyweight gain, minor haematological effects in females and slight impairment of single clinical chemistry parameters. The relative liver weights of both sexes and the relative kidney weights of the males were increased but without any histopathological correlation. The functional observation battery revealed no indication of any neurological impairment at any dose level. The No-Adverse-Effect-Level (NOAEL) for subacute toxicity in rats after 28-day oral treatment was 316 mg/kg bw. This value may be considered as the worst-case scenario for deoxyarbutin since the acidic stomach environment will lead to its degradation to hydroquinone which then causes the observed toxicity. Also in light of the pronounced route effect observed in the in vivo genotoxicity tests (see 3.3.6.), the SCCS concluded that the oral application route should be considered as inappropriate for investigating safety of desoxyarbutin in the contex","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw","noael_value":"316","page":43,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_019"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT=800; DOSE=For subchronic dermal treatment; the highest dose of 40% deoxyarbutin in propylene glycol/ethanol vehicle, corresponding to about 800 mg/kg bw, was the No-Adverse-Effect-Level (NOAEL) for systemic toxicity in male and female rabbits.; EFFECT=l investigated. The cumulative dermal irritation potential of deoxyarbutin cannot be assessed from these studies as the vehicle cream formulation led to more pronounced findings than the cream with 3% deoxyarbutin, and the propylene glycol/ethanol vehicle used in the 91-day study was per se irritating and led to chronic dermal inflammation. For subchronic dermal treatment; the highest dose of 40% deoxyarbutin in propylene glycol/ethanol vehicle, corresponding to about 800 mg/kg bw, was the No-Adverse-Effect-Level (NOAEL) for systemic toxicity in male and female rabbits. This value will be used for risk assessment and the calculation of the margin of safety (MoS). 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial reverse mutation assay Guideline/method: Comparable to OECD 471 Test system: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 and Escherichia coli strain WP2 uvrA and WP2 Replicates: triplicate plates Test substance: deoxyarbutin Batch: HT0059.01 Purity: 99.2%; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"For subchronic dermal treatment; the highest dose of 40% deoxyarbutin in propylene glycol/ethanol vehicle, corresponding to about 800 mg/kg bw, was the No-Adverse-Effect-Level (NOAEL) for systemic toxicity in male and female rabbits.","duration":"91-day","effect":"l investigated. The cumulative dermal irritation potential of deoxyarbutin cannot be assessed from these studies as the vehicle cream formulation led to more pronounced findings than the cream with 3% deoxyarbutin, and the propylene glycol/ethanol vehicle used in the 91-day study was per se irritating and led to chronic dermal inflammation. For subchronic dermal treatment; the highest dose of 40% deoxyarbutin in propylene glycol/ethanol vehicle, corresponding to about 800 mg/kg bw, was the No-Adverse-Effect-Level (NOAEL) for systemic toxicity in male and female rabbits. This value will be used for risk assessment and the calculation of the margin of safety (MoS). 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial reverse mutation assay Guideline/method: Comparable to OECD 471 Test system: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 and Escherichia coli strain WP2 uvrA and WP2 Replicates: triplicate plates Test substance: deoxyarbutin Batch: HT0059.01 Purity: 99.2%","endpoint":"repeated dose toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg bw","noael_value":"800","page":26,"route":"dermal","species":"rabbit","study_id":"sccs_o_183_noael_004"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 15; DOSE=30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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...; EFFECT=noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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. [HQ Refs. A, B]; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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...","duration":"28d","effect":"noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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. [HQ Refs. A, B]","endpoint":"reproductive toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 15","page":38,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_010"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 20; DOSE=Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied.; EFFECT=igmentation was reached, then topical treatment with 5% deoxyarbutin or HQ or tert-butylphenol containing emulsions was started. Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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":"53936-56-4","citation":"","dose":"Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied.","duration":"8 weeks","effect":"igmentation was reached, then topical treatment with 5% deoxyarbutin or HQ or tert-butylphenol containing emulsions was started. Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 20","page":38,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_005"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 20; DOSE=Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied.; EFFECT=reatment with 5% deoxyarbutin or HQ or tert-butylphenol containing emulsions was started. Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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":"53936-56-4","citation":"","dose":"Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied.","duration":"8 weeks","effect":"reatment with 5% deoxyarbutin or HQ or tert-butylphenol containing emulsions was started. Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 20","page":38,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_006"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 25; DOSE=30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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...; EFFECT=se-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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":"53936-56-4","citation":"","dose":"30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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...","duration":"8 weeks","effect":"se-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 25","page":38,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_008"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 74; DOSE=Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied.; EFFECT=t-butylphenol containing emulsions was started. Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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":"53936-56-4","citation":"","dose":"Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied.","duration":"8 weeks","effect":"t-butylphenol containing emulsions was started. Also the dose-response (0.1, 0.3, 1, 3%) and reversibility (8 weeks after termination of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 74","page":38,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_007"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 75; DOSE=30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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...; EFFECT=of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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. [HQ Refs. A, B]; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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...","duration":"28d","effect":"of treatment) were studied. No signs of inflammation or abnormal morphology were noted. Ref. 30 3.3.13 Information on the toxicity of hydroquinone Taken in part from the SCCP/1158/08 Opinion and updated in SCCS/1550/2015 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. [HQ Refs. A, B]","endpoint":"reproductive toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 75","page":38,"route":"oral","species":"rat","study_id":"sccs_o_183_noael_009"}

sccs_o_183.pdf

SOURCE_SUBDIR=sccs_o_183; REPORT_TITLE=OPINION ON deoxyarbutin Tetrahydropyranyloxy Phenol; OPINION_NUMBER=SCCS/1554/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=25 June 2015; VALUE_TEXT== 150; DOSE=NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).; EFFECT=Unlabeled table on page 38: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"53936-56-4","citation":"","dose":"NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","duration":"","effect":"Unlabeled table on page 38: NOEL (1-generation reproduction toxicity-rat) = 150 mg/kg/day (reproductive toxicity).","endpoint":"reproductive toxicity","ingredient":"Tetrahydropyranyloxy Phenol is a skin lightening agent synthesised through removal","loael_value":"","noael_unit":"mg/kg/day","noael_value":"= 150","page":38,"route":"","species":"rat","study_id":"sccs_o_183_noael_027"}

sccs_o_183.pdf