Alpha-Arbutin, Alpha-Arbutin; Beta-Arbutin, the safety of alpha-arbutin and

SOURCE_SUBDIR=sccs_o_264; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on the safety of alpha-arbutin and beta-arbutin in cosmetic products; OPINION_NUMBER=SCCS/1642/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 31 January 2023; VALUE_TEXT=100; DOSE=In the reproduction toxicity study with subcutaneous administration of beta-arbutin, the conservative NOAEL was 100 mg/kg bw/day (SCCS 2015).; EFFECT=. 3.4.2.2. SCCS comments on the safety evaluation of beta-arbutin by the applicant after the commenting period As no new data have been submitted by the applicant for beta-arbutin, calculations can only be done for beta-arbutin and for aggregate exposure of both arbutins, using for beta-arbutin the numbers as present in the SCCS opinion 2015. The maximum exposure to beta-arbutin is 6.8 μg/kg bw/day (SCCS 2015). In the reproduction toxicity study with subcutaneous administration of beta-arbutin, the conservative NOAEL was 100 mg/kg bw/day (SCCS 2015). If this NOAEL is applied, the MoS is 14700. 3.4.3 Hydroquinone 3.4.3.1. Safety evaluation of hydroquinone submitted by applicant during the commenting period ALPHA-ARBUTIN The exposure to hydroquinone via alpha- and/or beta-arbutin can occur via: 1. Cleavage of alpha- or beta-arbutin to hydroquinone in skin upon dermal penetration; 2. Hydroquinone as an impurity of alpha- or beta-arbutin; 3. Formation of hydroquinone from alpha- or beta-arbutin by skin microbiome on the skin.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84380-01-8","citation":"","dose":"In the reproduction toxicity study with subcutaneous administration of beta-arbutin, the conservative NOAEL was 100 mg/kg bw/day (SCCS 2015).","duration":"","effect":". 3.4.2.2. SCCS comments on the safety evaluation of beta-arbutin by the applicant after the commenting period As no new data have been submitted by the applicant for beta-arbutin, calculations can only be done for beta-arbutin and for aggregate exposure of both arbutins, using for beta-arbutin the numbers as present in the SCCS opinion 2015. The maximum exposure to beta-arbutin is 6.8 μg/kg bw/day (SCCS 2015). In the reproduction toxicity study with subcutaneous administration of beta-arbutin, the conservative NOAEL was 100 mg/kg bw/day (SCCS 2015). If this NOAEL is applied, the MoS is 14700. 3.4.3 Hydroquinone 3.4.3.1. Safety evaluation of hydroquinone submitted by applicant during the commenting period ALPHA-ARBUTIN The exposure to hydroquinone via alpha- and/or beta-arbutin can occur via: 1. Cleavage of alpha- or beta-arbutin to hydroquinone in skin upon dermal penetration; 2. Hydroquinone as an impurity of alpha- or beta-arbutin; 3. Formation of hydroquinone from alpha- or beta-arbutin by skin microbiome on the skin.","endpoint":"","ingredient":"Alpha-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":42,"route":"dermal","species":"","study_id":"sccs_o_264_noael_003"}

sccs_o_264.pdf

SOURCE_SUBDIR=sccs_o_264; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on the safety of alpha-arbutin and beta-arbutin in cosmetic products; OPINION_NUMBER=SCCS/1642/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 31 January 2023; VALUE_TEXT=100; DOSE=In the reproduction toxicity study with subcutaneous administration of beta-arbutin, the conservative NOAEL was 100 mg/kg bw/day (SCCS 2015).; EFFECT=on of beta-arbutin by the applicant after the commenting period As no new data have been submitted by the applicant for beta-arbutin, calculations can only be done for beta-arbutin and for aggregate exposure of both arbutins, using for beta-arbutin the numbers as present in the SCCS opinion 2015. The maximum exposure to beta-arbutin is 6.8 μg/kg bw/day (SCCS 2015). In the reproduction toxicity study with subcutaneous administration of beta-arbutin, the conservative NOAEL was 100 mg/kg bw/day (SCCS 2015). If this NOAEL is applied, the MoS is 14700. 3.4.3 Hydroquinone 3.4.3.1. Safety evaluation of hydroquinone submitted by applicant during the commenting period ALPHA-ARBUTIN The exposure to hydroquinone via alpha- and/or beta-arbutin can occur via: 1. Cleavage of alpha- or beta-arbutin to hydroquinone in skin upon dermal penetration; 2. Hydroquinone as an impurity of alpha- or beta-arbutin; 3. Formation of hydroquinone from alpha- or beta-arbutin by skin microbiome on the skin. The exposure to hydroquinone from each of these; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84380-01-8","citation":"","dose":"In the reproduction toxicity study with subcutaneous administration of beta-arbutin, the conservative NOAEL was 100 mg/kg bw/day (SCCS 2015).","duration":"","effect":"on of beta-arbutin by the applicant after the commenting period As no new data have been submitted by the applicant for beta-arbutin, calculations can only be done for beta-arbutin and for aggregate exposure of both arbutins, using for beta-arbutin the numbers as present in the SCCS opinion 2015. The maximum exposure to beta-arbutin is 6.8 μg/kg bw/day (SCCS 2015). In the reproduction toxicity study with subcutaneous administration of beta-arbutin, the conservative NOAEL was 100 mg/kg bw/day (SCCS 2015). If this NOAEL is applied, the MoS is 14700. 3.4.3 Hydroquinone 3.4.3.1. Safety evaluation of hydroquinone submitted by applicant during the commenting period ALPHA-ARBUTIN The exposure to hydroquinone via alpha- and/or beta-arbutin can occur via: 1. Cleavage of alpha- or beta-arbutin to hydroquinone in skin upon dermal penetration; 2. Hydroquinone as an impurity of alpha- or beta-arbutin; 3. Formation of hydroquinone from alpha- or beta-arbutin by skin microbiome on the skin. The exposure to hydroquinone from each of these","endpoint":"","ingredient":"Alpha-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":42,"route":"dermal","species":"","study_id":"sccs_o_264_noael_004"}

sccs_o_264.pdf

SOURCE_SUBDIR=sccs_o_264; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on the safety of alpha-arbutin and beta-arbutin in cosmetic products; OPINION_NUMBER=SCCS/1642/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 31 January 2023; VALUE_TEXT=15; DOSE=SED hydroquinone from beta-arbutin exposure is 45.8 μg /day or 0.763 μg /kg bw/day for a 60-kg person MoS calculations HQ-SED MoS SED conservative MoS conservativ e Repeated dose toxicity NOAEL 20 mg/kg bw/d Alpha-arbutin 0.00211 20/0.00211 =9500* 0.00211 9500* Beta-arbutin 0.000763 (2015opinion) 26200* 0.003853 (+microbiom e) 5200* Aggregate de...; EFFECT=Beta-Arbutin, and therefore the exposure to hydroquinone is taken from the SCCS 2015 opinion. SED hydroquinone from beta-arbutin exposure is 45.8 μg /day or 0.763 μg /kg bw/day for a 60-kg person MoS calculations HQ-SED MoS SED conservative MoS conservativ e Repeated dose toxicity NOAEL 20 mg/kg bw/d Alpha-arbutin 0.00211 20/0.00211 =9500* 0.00211 9500* Beta-arbutin 0.000763 (2015opinion) 26200* 0.003853 (+microbiom e) 5200* Aggregate deterministic exposure 0.00287 7000* 0.005963 3300* Reproduction toxicity NOAEL 15 mg/kg bw/d Alpha-arbutin 0.00211 15/0.00211 =7100* 0.00211 9500* Beta-arbutin 0.000763 19700* 0.003853 3900*; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84380-01-8","citation":"","dose":"SED hydroquinone from beta-arbutin exposure is 45.8 μg /day or 0.763 μg /kg bw/day for a 60-kg person MoS calculations HQ-SED MoS SED conservative MoS conservativ e Repeated dose toxicity NOAEL 20 mg/kg bw/d Alpha-arbutin 0.00211 20/0.00211 =9500* 0.00211 9500* Beta-arbutin 0.000763 (2015opinion) 26200* 0.003853 (+microbiom e) 5200* Aggregate de...","duration":"","effect":"Beta-Arbutin, and therefore the exposure to hydroquinone is taken from the SCCS 2015 opinion. SED hydroquinone from beta-arbutin exposure is 45.8 μg /day or 0.763 μg /kg bw/day for a 60-kg person MoS calculations HQ-SED MoS SED conservative MoS conservativ e Repeated dose toxicity NOAEL 20 mg/kg bw/d Alpha-arbutin 0.00211 20/0.00211 =9500* 0.00211 9500* Beta-arbutin 0.000763 (2015opinion) 26200* 0.003853 (+microbiom e) 5200* Aggregate deterministic exposure 0.00287 7000* 0.005963 3300* Reproduction toxicity NOAEL 15 mg/kg bw/d Alpha-arbutin 0.00211 15/0.00211 =7100* 0.00211 9500* Beta-arbutin 0.000763 19700* 0.003853 3900*","endpoint":"repeated dose toxicity","ingredient":"Alpha-Arbutin","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"15","page":43,"route":"","species":"","study_id":"sccs_o_264_noael_006"}

sccs_o_264.pdf

SOURCE_SUBDIR=sccs_o_264; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on the safety of alpha-arbutin and beta-arbutin in cosmetic products; OPINION_NUMBER=SCCS/1642/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 31 January 2023; VALUE_TEXT=20; DOSE=SED hydroquinone from beta-arbutin exposure is 45.8 μg /day or 0.763 μg /kg bw/day for a 60-kg person MoS calculations HQ-SED MoS SED conservative MoS conservativ e Repeated dose toxicity NOAEL 20 mg/kg bw/d Alpha-arbutin 0.00211 20/0.00211 =9500* 0.00211 9500* Beta-arbutin 0.000763 (2015opinion) 26200* 0.003853 (+microbiom e) 5200* Aggregate de...; EFFECT=RBUTIN upon absorption) 1.23 μg/kg bw/day 2 (impurity of ALPHA-ARBUTIN) 0.00175 μg/kg bw/day 3 (formation from ALPHA-ARBUTIN via skin microbiome) 0.883 μg/kg bw/day Total 2.11 μg/kg bw/day BETA-ARBUTIN No new data are available for Beta-Arbutin, and therefore the exposure to hydroquinone is taken from the SCCS 2015 opinion. SED hydroquinone from beta-arbutin exposure is 45.8 μg /day or 0.763 μg /kg bw/day for a 60-kg person MoS calculations HQ-SED MoS SED conservative MoS conservativ e Repeated dose toxicity NOAEL 20 mg/kg bw/d Alpha-arbutin 0.00211 20/0.00211 =9500* 0.00211 9500* Beta-arbutin 0.000763 (2015opinion) 26200* 0.003853 (+microbiom e) 5200* Aggregate deterministic exposure 0.00287 7000* 0.005963 3300* Reproduction toxicity NOAEL 15 mg/kg bw/d Alpha-arbutin 0.00211 15/0.00211 =7100* 0.00211 9500* Beta-arbutin 0.000763 19700* 0.003853 3900*; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84380-01-8","citation":"","dose":"SED hydroquinone from beta-arbutin exposure is 45.8 μg /day or 0.763 μg /kg bw/day for a 60-kg person MoS calculations HQ-SED MoS SED conservative MoS conservativ e Repeated dose toxicity NOAEL 20 mg/kg bw/d Alpha-arbutin 0.00211 20/0.00211 =9500* 0.00211 9500* Beta-arbutin 0.000763 (2015opinion) 26200* 0.003853 (+microbiom e) 5200* Aggregate de...","duration":"","effect":"RBUTIN upon absorption) 1.23 μg/kg bw/day 2 (impurity of ALPHA-ARBUTIN) 0.00175 μg/kg bw/day 3 (formation from ALPHA-ARBUTIN via skin microbiome) 0.883 μg/kg bw/day Total 2.11 μg/kg bw/day BETA-ARBUTIN No new data are available for Beta-Arbutin, and therefore the exposure to hydroquinone is taken from the SCCS 2015 opinion. SED hydroquinone from beta-arbutin exposure is 45.8 μg /day or 0.763 μg /kg bw/day for a 60-kg person MoS calculations HQ-SED MoS SED conservative MoS conservativ e Repeated dose toxicity NOAEL 20 mg/kg bw/d Alpha-arbutin 0.00211 20/0.00211 =9500* 0.00211 9500* Beta-arbutin 0.000763 (2015opinion) 26200* 0.003853 (+microbiom e) 5200* Aggregate deterministic exposure 0.00287 7000* 0.005963 3300* Reproduction toxicity NOAEL 15 mg/kg bw/d Alpha-arbutin 0.00211 15/0.00211 =7100* 0.00211 9500* Beta-arbutin 0.000763 19700* 0.003853 3900*","endpoint":"repeated dose toxicity","ingredient":"Alpha-Arbutin","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"20","page":43,"route":"","species":"","study_id":"sccs_o_264_noael_005"}

sccs_o_264.pdf

SOURCE_SUBDIR=sccs_o_264; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on the safety of alpha-arbutin and beta-arbutin in cosmetic products; OPINION_NUMBER=SCCS/1642/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 31 January 2023; VALUE_TEXT=1000; DOSE=Overall conclusion on repeated dose toxicity for beta-arbutin As no new data is available and only a repeated dose 28-day oral study and 90-day dermal study with the rat revealed some sporadic observations that could not be related to beta- arbutin, the highest dosage tested of these studies was designated as NOEL, i.e.1000 mg/kg bw/day for the...; EFFECT=ble, therefore a MoS for alpha-arbutin cannot be calculated. (SCCS/1552/15) Beta-arbutin: In SCCS/1550/15 only limited data was present; no new data was submitted, and no open literature data is available. Overall conclusion on repeated dose toxicity for beta-arbutin As no new data is available and only a repeated dose 28-day oral study and 90-day dermal study with the rat revealed some sporadic observations that could not be related to beta- arbutin, the highest dosage tested of these studies was 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. (SCCS/1550/15) 3.3.5 genotoxicity/mutagenicity Alpha-arbutin The genotoxicity of alpha-arbutin has been investigated in genotoxicity tests for gene mutations in bacteria and for structural and numerical chromosomal aberrations in an in vivo micronucleus test. Alpha-arbutin did not induce gene mutations in bacteria nor an increase in cells with micronuclei in bone marrow cells of mice. Based on this l; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84380-01-8","citation":"","dose":"Overall conclusion on repeated dose toxicity for beta-arbutin As no new data is available and only a repeated dose 28-day oral study and 90-day dermal study with the rat revealed some sporadic observations that could not be related to beta- arbutin, the highest dosage tested of these studies was designated as NOEL, i.e.1000 mg/kg bw/day for the...","duration":"28-day","effect":"ble, therefore a MoS for alpha-arbutin cannot be calculated. (SCCS/1552/15) Beta-arbutin: In SCCS/1550/15 only limited data was present; no new data was submitted, and no open literature data is available. Overall conclusion on repeated dose toxicity for beta-arbutin As no new data is available and only a repeated dose 28-day oral study and 90-day dermal study with the rat revealed some sporadic observations that could not be related to beta- arbutin, the highest dosage tested of these studies was 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. (SCCS/1550/15) 3.3.5 genotoxicity/mutagenicity Alpha-arbutin The genotoxicity of alpha-arbutin has been investigated in genotoxicity tests for gene mutations in bacteria and for structural and numerical chromosomal aberrations in an in vivo micronucleus test. Alpha-arbutin did not induce gene mutations in bacteria nor an increase in cells with micronuclei in bone marrow cells of mice. Based on this l","endpoint":"repeated dose toxicity","ingredient":"Alpha-Arbutin","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":37,"route":"oral","species":"rat","study_id":"sccs_o_264_noael_002"}

sccs_o_264.pdf

SOURCE_SUBDIR=sccs_o_264; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on the safety of alpha-arbutin and beta-arbutin in cosmetic products; OPINION_NUMBER=SCCS/1642/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 31 January 2023; VALUE_TEXT=unclear:SCCS/1550/15) 3.3.4 Repeated dose toxicity Alpha-arbutin: no conclusive data was available in the SCCS/1552/15 Opinion; no new data was submitted, and no open literature data are available. Overall conclusion on repeated dose toxicity for alpha-arbutin Only one study with repeated dermal application of alpha-arbutin was available in SCCS/1552/15. Due to its focus on irritation and the limited number of animals (3 guinea pigs of each sex), it is not suitable for conclusions on systemic effects or derivation of a NOAEL. No new data are available, therefore a MoS for alpha-arbutin cannot be calculated. (SCCS/1552/15) Beta-arbutin: In SCCS/1550/15 only limited data was present; no new data was submitted, and no open literature data is available. Overall conclusion on repeated dose toxicity for beta-arbutin As no new data is available and only a repeated dose 28-day oral study and 90-day dermal study with the rat revealed some sporadic observations that could not be related to beta- arbutin, the highest dosage tested of these st; DOSE=SCCS/1550/15) 3.3.4 Repeated dose toxicity Alpha-arbutin: no conclusive data was available in the SCCS/1552/15 Opinion; no new data was submitted, and no open literature data are available.; EFFECT=SCCS-rejected applicant NOAEL: SCCS/1550/15) 3.3.4 Repeated dose toxicity Alpha-arbutin: no conclusive data was available in the SCCS/1552/15 Opinion; no new data was submitted, and no open literature data are available. Overall conclusion on repeated dose toxicity for alpha-arbutin Only one study with repeated dermal application of alpha-arbutin was available in SCCS/1552/15. Due to its focus on irritation and the limited number of animals (3 guinea pigs of each sex), it is not suitable for conclusions on systemic effects or derivation of a NOAEL. No new data are available, therefore a MoS for alpha-arbutin cannot be calculated. (SCCS/1552/15) Beta-arbutin: In SCCS/1550/15 only limited data was present; no new data was submitted, and no open literature data is available. Overall conclusion on repeated dose toxicity for beta-arbutin As no new data is available and only a repeated dose 28-day oral study and 90-day dermal study with the rat revealed some sporadic observations that could not be related to beta- arbutin, the highest dosage tested of these st; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84380-01-8","citation":"","dose":"SCCS/1550/15) 3.3.4 Repeated dose toxicity Alpha-arbutin: no conclusive data was available in the SCCS/1552/15 Opinion; no new data was submitted, and no open literature data are available.","duration":"28-day","effect":"SCCS-rejected applicant NOAEL: SCCS/1550/15) 3.3.4 Repeated dose toxicity Alpha-arbutin: no conclusive data was available in the SCCS/1552/15 Opinion; no new data was submitted, and no open literature data are available. Overall conclusion on repeated dose toxicity for alpha-arbutin Only one study with repeated dermal application of alpha-arbutin was available in SCCS/1552/15. Due to its focus on irritation and the limited number of animals (3 guinea pigs of each sex), it is not suitable for conclusions on systemic effects or derivation of a NOAEL. No new data are available, therefore a MoS for alpha-arbutin cannot be calculated. (SCCS/1552/15) Beta-arbutin: In SCCS/1550/15 only limited data was present; no new data was submitted, and no open literature data is available. Overall conclusion on repeated dose toxicity for beta-arbutin As no new data is available and only a repeated dose 28-day oral study and 90-day dermal study with the rat revealed some sporadic observations that could not be related to beta- arbutin, the highest dosage tested of these st","endpoint":"repeated dose toxicity","ingredient":"Alpha-Arbutin","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1550/15) 3.3.4 Repeated dose toxicity Alpha-arbutin: no conclusive data was available in the SCCS/1552/15 Opinion; no new data was submitted, and no open literature data are available. Overall conclusion on repeated dose toxicity for alpha-arbutin Only one study with repeated dermal application of alpha-arbutin was available in SCCS/1552/15. Due to its focus on irritation and the limited number of animals (3 guinea pigs of each sex), it is not suitable for conclusions on systemic effects or derivation of a NOAEL. No new data are available, therefore a MoS for alpha-arbutin cannot be calculated. (SCCS/1552/15) Beta-arbutin: In SCCS/1550/15 only limited data was present; no new data was submitted, and no open literature data is available. Overall conclusion on repeated dose toxicity for beta-arbutin As no new data is available and only a repeated dose 28-day oral study and 90-day dermal study with the rat revealed some sporadic observations that could not be related to beta- arbutin, the highest dosage tested of these st","page":37,"route":"oral","species":"rat","study_id":"sccs_o_264_noael_001"}

sccs_o_264.pdf