Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6), codes ................................................ 9, s through damaged skin. Also, Hexyl Salicylate is classified as a

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=180; DOSE=Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).; EFFECT=er. However, for awareness and completeness, there is evidence on other simple alkyl salicylates that can add to the confidence of the outcome from the safety evaluation performed in this dossier. Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).","duration":"","effect":"er. However, for awareness and completeness, there is evidence on other simple alkyl salicylates that can add to the confidence of the outcome from the safety evaluation performed in this dossier. Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6","endpoint":"","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"180","page":39,"route":"","species":"rat","study_id":"sccs_o_281_final_noael_006"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=180; DOSE=Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).; EFFECT=ation performed in this dossier. Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).","duration":"","effect":"ation performed in this dossier. Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6","endpoint":"","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"180","page":39,"route":"","species":"rat","study_id":"sccs_o_281_final_noael_008"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=370; DOSE=for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966).; EFFECT=for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientific Associates, 1966). Although this study had some methodology discrepancies, it is still considered to be reliable (Klimisch score 2). • Dermal route No data reported on 1-hexanol • Inhalation There are no data for Hexyl Salicylate that were generated before March 2013. Reference to the similar ingredient methyl salicylate is provided below. Methyl salicylate Gage (1970) reported a study on methyl salicylat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966).","duration":"13-week","effect":"for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientific Associates, 1966). Although this study had some methodology discrepancies, it is still considered to be reliable (Klimisch score 2). • Dermal route No data reported on 1-hexanol • Inhalation There are no data for Hexyl Salicylate that were generated before March 2013. Reference to the similar ingredient methyl salicylate is provided below. Methyl salicylate Gage (1970) reported a study on methyl salicylat","endpoint":"","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"370","page":38,"route":"oral","species":"rat","study_id":"sccs_o_281_final_noael_005"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=540; DOSE=Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).; EFFECT=at can add to the confidence of the outcome from the safety evaluation performed in this dossier. Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).","duration":"","effect":"at can add to the confidence of the outcome from the safety evaluation performed in this dossier. Cyclohexyl Salicylate An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6","endpoint":"","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"540","page":39,"route":"","species":"rat","study_id":"sccs_o_281_final_noael_007"}

sccs_o_281_final.pdf

{"dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1...","effect":"SCCS/1658/23 Final version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientif","page":38,"pdf":"sccs_o_281_final.pdf","row_type":"noael_study","study_id":"sccs_o_281_final_noael_002"}

sccs_o_281_final.pdf

{"dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1...","effect":"SCCS/1658/23 Final version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientif","page":38,"pdf":"sccs_o_281_final.pdf","row_type":"noael_study","study_id":"sccs_o_281_final_noael_002"}

sccs_o_281_final.pdf

{"dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1...","effect":"SCCS/1658/23 Final version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientif","page":38,"pdf":"sccs_o_281_final.pdf","row_type":"noael_study","study_id":"sccs_o_281_final_noael_002"}

sccs_o_281_final.pdf

{"dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1...","effect":"SCCS/1658/23 Final version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientif","page":38,"pdf":"sccs_o_281_final.pdf","row_type":"noael_study","study_id":"sccs_o_281_final_noael_002"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=75; DOSE=For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). The developmental effects observed in this study are the most sensitive effects after repeated exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) and is also supported by Tanaka et al. (1973b).’ In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys = 75 mg/kg bw/day. A salicylic acid equivalent SED; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). The developmental effects observed in this study are the most sensitive effects after repeated exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) and is also supported by Tanaka et al. (1973b).’ In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys = 75 mg/kg bw/day. A salicylic acid equivalent SED","endpoint":"developmental toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":40,"route":"oral","species":"human","study_id":"sccs_o_281_final_noael_010"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=75; DOSE=For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=maging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). The developmental effects observed in this study are the most sensitive effects after repeated exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) and is also supported by Tanaka et al. (1973b).’ In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys = 75 mg/kg bw/day. A salicylic acid equivalent SED can be calculated and compared with this POD as; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"maging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). The developmental effects observed in this study are the most sensitive effects after repeated exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) and is also supported by Tanaka et al. (1973b).’ In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys = 75 mg/kg bw/day. A salicylic acid equivalent SED can be calculated and compared with this POD as","endpoint":"developmental toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":40,"route":"oral","species":"human","study_id":"sccs_o_281_final_noael_011"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=75; DOSE=For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=ed were reviewed for the purposes of performing a cosmetics safety assessment. SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys = 75 mg/kg bw/day. A salicylic acid equivalent SED; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"ed were reviewed for the purposes of performing a cosmetics safety assessment. SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys = 75 mg/kg bw/day. A salicylic acid equivalent SED","endpoint":"developmental toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":53,"route":"oral","species":"human","study_id":"sccs_o_281_final_noael_015"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=75; DOSE=For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=a cosmetics safety assessment. SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys = 75 mg/kg bw/day. A salicylic acid equivalent SED can be calculated and compared with this POD.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"a cosmetics safety assessment. SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys = 75 mg/kg bw/day. A salicylic acid equivalent SED can be calculated and compared with this POD.","endpoint":"developmental toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":53,"route":"oral","species":"human","study_id":"sccs_o_281_final_noael_016"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=1000; DOSE=te and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966).; EFFECT=te and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientific Associates, 1966). Although this study had some methodology discrepancies, it is still considered to be reliable (Klimisch score 2). • Dermal route No data reported on 1-hexanol • Inhalation There are no data for Hexyl Salicylate that were generated before March 2013. Reference to the simi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"te and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966).","duration":"sub-chronic","effect":"te and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientific Associates, 1966). Although this study had some methodology discrepancies, it is still considered to be reliable (Klimisch score 2). • Dermal route No data reported on 1-hexanol • Inhalation There are no data for Hexyl Salicylate that were generated before March 2013. Reference to the simi","endpoint":"repeated dose toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":38,"route":"oral","species":"rat","study_id":"sccs_o_281_final_noael_004"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=1127; DOSE=6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1...; EFFECT=SCCS/1658/23 Final version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientif; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1...","duration":"sub-acute","effect":"SCCS/1658/23 Final version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientif","endpoint":"repeated dose toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg","noael_value":"1127","page":38,"route":"oral","species":"rat","study_id":"sccs_o_281_final_noael_002"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=1127; DOSE=6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1...; EFFECT=S/1658/23 Final version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientific Asso; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1...","duration":"sub-acute","effect":"S/1658/23 Final version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 38 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 1-Hexanol • Oral route As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study. The results of this key study are supported by the reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day for female dogs (study reported as by Scientific Asso","endpoint":"repeated dose toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg","noael_value":"1127","page":38,"route":"oral","species":"rat","study_id":"sccs_o_281_final_noael_003"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=0.1; DOSE=For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=s main metabolites, salicylic acid and 1-hexanol, to which the body may be principally exposed. Since 1-hexanol is not classified for reproductive toxicity, the focus is on the more relevant metabolite salicylic acid data. SCCS comments The SCCS agrees that salicylic acid is a developmental toxicant. Harmonised classification of salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). The developmental effects observed in this study are the most sensitive effects after repeated exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) and is also supported by Tanaka et al. (1973b).’ In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can ac; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"s main metabolites, salicylic acid and 1-hexanol, to which the body may be principally exposed. Since 1-hexanol is not classified for reproductive toxicity, the focus is on the more relevant metabolite salicylic acid data. SCCS comments The SCCS agrees that salicylic acid is a developmental toxicant. Harmonised classification of salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). The developmental effects observed in this study are the most sensitive effects after repeated exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) and is also supported by Tanaka et al. (1973b).’ In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can ac","endpoint":"reproductive toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"%","noael_value":"0.1","page":40,"route":"oral","species":"human","study_id":"sccs_o_281_final_noael_009"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=0.1; DOSE=For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=ble reproductive/developmental toxicity data and conclusions for the primary metabolite salicylic acid and 1-hexanol to which the body may be principally exposed were reviewed for the purposes of performing a cosmetics safety assessment. SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexa; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"ble reproductive/developmental toxicity data and conclusions for the primary metabolite salicylic acid and 1-hexanol to which the body may be principally exposed were reviewed for the purposes of performing a cosmetics safety assessment. SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexa","endpoint":"reproductive toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"%","noael_value":"0.1","page":53,"route":"oral","species":"human","study_id":"sccs_o_281_final_noael_014"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=75; DOSE=The POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic effects, in the Tanaka et al.; EFFECT=en that Hexyl Salicylate itself is not regarded as the main toxicant, but rather salicylic acid as the chief hydrolysis product via all routes of exposure, it is possible to perform a cosmetic safety evaluation for Hexyl Salicylate using the study by Tanaka et al. 1973 (from the reproductive/developmental data shown in section 3.4.5) for its principal primary metabolite, salicylic acid. Salicylic acid was reviewed recently by the SCCS in its Opinion from December 2023. The POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic effects, in the Tanaka et al. 1973 study. A value for skin penetration of 13.4% (mean (3.04 +1SD) x a correction factor of 3) has been used in all calculations of systemic exposure dose for dermally applied products (see section 3.2.2). • MoS for adults Based on the exposure information in section 3.2, the Margins of Safety for consumer exposures to Hexyl Salicylate in 18 cosmetic products are shown in Table 1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"The POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic effects, in the Tanaka et al.","duration":"developmental","effect":"en that Hexyl Salicylate itself is not regarded as the main toxicant, but rather salicylic acid as the chief hydrolysis product via all routes of exposure, it is possible to perform a cosmetic safety evaluation for Hexyl Salicylate using the study by Tanaka et al. 1973 (from the reproductive/developmental data shown in section 3.4.5) for its principal primary metabolite, salicylic acid. Salicylic acid was reviewed recently by the SCCS in its Opinion from December 2023. The POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic effects, in the Tanaka et al. 1973 study. A value for skin penetration of 13.4% (mean (3.04 +1SD) x a correction factor of 3) has been used in all calculations of systemic exposure dose for dermally applied products (see section 3.2.2). • MoS for adults Based on the exposure information in section 3.2, the Margins of Safety for consumer exposures to Hexyl Salicylate in 18 cosmetic products are shown in Table 1","endpoint":"reproductive toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"75","page":49,"route":"","species":"rat","study_id":"sccs_o_281_final_noael_012"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=75; DOSE=The POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic effects, in the Tanaka et al.; EFFECT=not regarded as the main toxicant, but rather salicylic acid as the chief hydrolysis product via all routes of exposure, it is possible to perform a cosmetic safety evaluation for Hexyl Salicylate using the study by Tanaka et al. 1973 (from the reproductive/developmental data shown in section 3.4.5) for its principal primary metabolite, salicylic acid. Salicylic acid was reviewed recently by the SCCS in its Opinion from December 2023. The POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic effects, in the Tanaka et al. 1973 study. A value for skin penetration of 13.4% (mean (3.04 +1SD) x a correction factor of 3) has been used in all calculations of systemic exposure dose for dermally applied products (see section 3.2.2). • MoS for adults Based on the exposure information in section 3.2, the Margins of Safety for consumer exposures to Hexyl Salicylate in 18 cosmetic products are shown in Table 16 below; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"The POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic effects, in the Tanaka et al.","duration":"developmental","effect":"not regarded as the main toxicant, but rather salicylic acid as the chief hydrolysis product via all routes of exposure, it is possible to perform a cosmetic safety evaluation for Hexyl Salicylate using the study by Tanaka et al. 1973 (from the reproductive/developmental data shown in section 3.4.5) for its principal primary metabolite, salicylic acid. Salicylic acid was reviewed recently by the SCCS in its Opinion from December 2023. The POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic effects, in the Tanaka et al. 1973 study. A value for skin penetration of 13.4% (mean (3.04 +1SD) x a correction factor of 3) has been used in all calculations of systemic exposure dose for dermally applied products (see section 3.2.2). • MoS for adults Based on the exposure information in section 3.2, the Margins of Safety for consumer exposures to Hexyl Salicylate in 18 cosmetic products are shown in Table 16 below","endpoint":"reproductive toxicity","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"75","page":49,"route":"","species":"rat","study_id":"sccs_o_281_final_noael_013"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281_final; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 28 February 2024; VALUE_TEXT=35,433; DOSE=Substances in Category 4 are rarely important clinical allergens, because they require considerable/prolonged exposure to higher dose levels to pr; EFFECT=ere kept dry for approximately 24 h and then removed. A series of nine induction applications were completed over a period of three weeks. A rest period of approximately 2 weeks followed the last induction. At the challenge phase, patches were applied as in the induction phase and kept in place for 24 h, after which time they were removed and the challenge sites were scored. The test sites were also scored at 48, 72 and 96 h post-patching. No sensitisation reactions were observed (RIFM (Harrison), 2004). The HRIPT NOEL was therefore 35,433 μg/cm2. Hexyl Salicylate has been classified as a Category 4 substance (infrequent cause of contact allergy in relation to level of exposure) with regard to its human skin sensitisation potential (Basketter et al., 2014). This classification by authors of the study is based on an analysis of human data adapted from a number of published references. Substances in Category 4 are rarely important clinical allergens, because they require considerable/prolonged exposure to higher dose levels to pr; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"Substances in Category 4 are rarely important clinical allergens, because they require considerable/prolonged exposure to higher dose levels to pr","duration":"2 weeks","effect":"ere kept dry for approximately 24 h and then removed. A series of nine induction applications were completed over a period of three weeks. A rest period of approximately 2 weeks followed the last induction. At the challenge phase, patches were applied as in the induction phase and kept in place for 24 h, after which time they were removed and the challenge sites were scored. The test sites were also scored at 48, 72 and 96 h post-patching. No sensitisation reactions were observed (RIFM (Harrison), 2004). The HRIPT NOEL was therefore 35,433 μg/cm2. Hexyl Salicylate has been classified as a Category 4 substance (infrequent cause of contact allergy in relation to level of exposure) with regard to its human skin sensitisation potential (Basketter et al., 2014). This classification by authors of the study is based on an analysis of human data adapted from a number of published references. Substances in Category 4 are rarely important clinical allergens, because they require considerable/prolonged exposure to higher dose levels to pr","endpoint":"sensitisation","ingredient":"Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6)","loael_value":"","noael_unit":"μg/cm2","noael_value":"35,433","page":35,"route":"","species":"human","study_id":"sccs_o_281_final_noael_001"}

sccs_o_281_final.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=unclear:Table 15: Deterministic worst-case margin of safety calculations for the dermal and oral route: 29 | POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75; EFFECT=Table 15: Deterministic worst-case margin of safety calculations for the dermal and oral route: 29 | POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"","duration":"","effect":"Table 15: Deterministic worst-case margin of safety calculations for the dermal and oral route: 29 | POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"","noael_value":"unclear:Table 15: Deterministic worst-case margin of safety calculations for the dermal and oral route: 29 | POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75","page":45,"route":"oral","species":"","study_id":"sccs_o_281_noael_017"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=180; DOSE=28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).; EFFECT=and completeness, there is evidence on other simple alkyl salicylates 26 that can add to the confidence of the outcome from the safety evaluation performed in this 27 dossier. 28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 33 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 34 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this 35 dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. 36 With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, 37 growth and behaviour were seen at the top dose. 38 39 An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). 40 Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 41 to 15 of gestation. A standard dose volum; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).","duration":"","effect":"and completeness, there is evidence on other simple alkyl salicylates 26 that can add to the confidence of the outcome from the safety evaluation performed in this 27 dossier. 28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 33 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 34 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this 35 dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. 36 With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, 37 growth and behaviour were seen at the top dose. 38 39 An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). 40 Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 41 to 15 of gestation. A standard dose volum","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"180","page":36,"route":"","species":"rat","study_id":"sccs_o_281_noael_006"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=370; DOSE=a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966).; EFFECT=a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study reported as by Scientific Associates, 1966). Although this study had 15 some methodology discrepancies, it is still considered to be reliable (Klimisch score 2). 16 17 • Dermal route 18 19 No data reported on 1-hexanol 20 21 • Inhalation 22 23 There are no data for Hexyl Salicylate that were generated before March 2013. Reference to 24 the similar ingredient methyl salicylate is provided below. 25 26 Methyl salicylate 27 28 Gag; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966).","duration":"13-week","effect":"a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study reported as by Scientific Associates, 1966). Although this study had 15 some methodology discrepancies, it is still considered to be reliable (Klimisch score 2). 16 17 • Dermal route 18 19 No data reported on 1-hexanol 20 21 • Inhalation 22 23 There are no data for Hexyl Salicylate that were generated before March 2013. Reference to 24 the similar ingredient methyl salicylate is provided below. 25 26 Methyl salicylate 27 28 Gag","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"370","page":35,"route":"oral","species":"rat","study_id":"sccs_o_281_noael_005"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=540; DOSE=28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).; EFFECT=e of the outcome from the safety evaluation performed in this 27 dossier. 28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 33 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 34 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this 35 dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. 36 With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, 37 growth and behaviour were seen at the top dose. 38 39 An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). 40 Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 41 to 15 of gestation. A standard dose volume of 5ml/kg bw was used. Each group was n=24 42 female rats. There were no effects of treatment seen in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).","duration":"","effect":"e of the outcome from the safety evaluation performed in this 27 dossier. 28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 33 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 34 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this 35 dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. 36 With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, 37 growth and behaviour were seen at the top dose. 38 39 An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). 40 Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 41 to 15 of gestation. A standard dose volume of 5ml/kg bw was used. Each group was n=24 42 female rats. There were no effects of treatment seen in","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"540","page":36,"route":"","species":"rat","study_id":"sccs_o_281_noael_007"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=1000; DOSE=l / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966).; EFFECT=l / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study reported as by Scientific Associates, 1966). Although this study had 15 some methodology discrepancies, it is still considered to be reliable (Klimisch score 2). 16 17 • Dermal route 18 19 No data reported on 1-hexanol 20 21 • Inhalation 22 23 There are no data for Hexyl Salicylate that were generated befo; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"l / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966).","duration":"13-week","effect":"l / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study reported as by Scientific Associates, 1966). Although this study had 15 some methodology discrepancies, it is still considered to be reliable (Klimisch score 2). 16 17 • Dermal route 18 19 No data reported on 1-hexanol 20 21 • Inhalation 22 23 There are no data for Hexyl Salicylate that were generated befo","endpoint":"","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":35,"route":"oral","species":"rat","study_id":"sccs_o_281_noael_004"}

sccs_o_281.pdf

{"dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH...","effect":"SCCS/1658/23 Preliminary version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study report","page":35,"pdf":"sccs_o_281.pdf","row_type":"noael_study","study_id":"sccs_o_281_noael_002"}

sccs_o_281.pdf

{"dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH...","effect":"SCCS/1658/23 Preliminary version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study report","page":35,"pdf":"sccs_o_281.pdf","row_type":"noael_study","study_id":"sccs_o_281_noael_002"}

sccs_o_281.pdf

{"dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH...","effect":"SCCS/1658/23 Preliminary version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study report","page":35,"pdf":"sccs_o_281.pdf","row_type":"noael_study","study_id":"sccs_o_281_noael_002"}

sccs_o_281.pdf

{"dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH...","effect":"SCCS/1658/23 Preliminary version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study report","page":35,"pdf":"sccs_o_281.pdf","row_type":"noael_study","study_id":"sccs_o_281_noael_002"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=0.1; DOSE=For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=mental toxicity data and 35 conclusions for the primary metabolite salicylic acid and 1-hexanol to which the body may be 36 principally exposed were reviewed for the purposes of performing a cosmetics safety 37 assessment. 38 39 SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of 40 salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 41 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 43 44 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 45 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 46 47 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 48 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 49 is made that 100% of Hexyl Salicylate is metabolised to sali; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"mental toxicity data and 35 conclusions for the primary metabolite salicylic acid and 1-hexanol to which the body may be 36 principally exposed were reviewed for the purposes of performing a cosmetics safety 37 assessment. 38 39 SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of 40 salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 41 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 43 44 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 45 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 46 47 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 48 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 49 is made that 100% of Hexyl Salicylate is metabolised to sali","endpoint":"developmental toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"%","noael_value":"0.1","page":48,"route":"oral","species":"human","study_id":"sccs_o_281_noael_014"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=75; DOSE=For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 21 The developmental effects observed in this study are the most sensitive effects after repeated 22 exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) 23 and is also supported by Tanaka et al. (1973b).’ 24 25 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 26 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 27 28 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 29 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 30 is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and 31 salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys 32 = 75 mg/kg bw/day. A salicyli; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 21 The developmental effects observed in this study are the most sensitive effects after repeated 22 exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) 23 and is also supported by Tanaka et al. (1973b).’ 24 25 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 26 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 27 28 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 29 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 30 is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and 31 salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys 32 = 75 mg/kg bw/day. A salicyli","endpoint":"developmental toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":37,"route":"oral","species":"human","study_id":"sccs_o_281_noael_010"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=75; DOSE=For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=ld). For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 21 The developmental effects observed in this study are the most sensitive effects after repeated 22 exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) 23 and is also supported by Tanaka et al. (1973b).’ 24 25 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 26 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 27 28 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 29 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 30 is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and 31 salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys 32 = 75 mg/kg bw/day. A salicylic acid equivalent SED can be calculated and compare; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"ld). For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 21 The developmental effects observed in this study are the most sensitive effects after repeated 22 exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) 23 and is also supported by Tanaka et al. (1973b).’ 24 25 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 26 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 27 28 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 29 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 30 is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and 31 salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys 32 = 75 mg/kg bw/day. A salicylic acid equivalent SED can be calculated and compare","endpoint":"developmental toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":37,"route":"oral","species":"human","study_id":"sccs_o_281_noael_011"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=75; DOSE=For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=purposes of performing a cosmetics safety 37 assessment. 38 39 SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of 40 salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 41 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 43 44 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 45 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 46 47 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 48 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 49 is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and 50 salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys 51 = 75 mg/kg bw/day. A salicyli; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"purposes of performing a cosmetics safety 37 assessment. 38 39 SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of 40 salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 41 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 43 44 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 45 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 46 47 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 48 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 49 is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and 50 salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys 51 = 75 mg/kg bw/day. A salicyli","endpoint":"developmental toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":48,"route":"oral","species":"human","study_id":"sccs_o_281_noael_015"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=75; DOSE=For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=sment. 38 39 SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of 40 salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 41 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 43 44 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 45 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 46 47 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 48 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 49 is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and 50 salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys 51 = 75 mg/kg bw/day. A salicylic acid equivalent SED can be calculated and compare; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"sment. 38 39 SCCS considers that salicylic acid is a developmental toxicant. Harmonised classification of 40 salicylic acid was recently published in Regulation 2018/1480 and is classified as Repr. 2 41 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses the 42 developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 43 44 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 45 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 46 47 This POD for salicylic acid can act as a conservative surrogate POD for Hexyl Salicylate. On a 48 molar basis, 1 mole of Hexyl Salicylate is converted to 1 mole of salicylic acid. An assumption 49 is made that 100% of Hexyl Salicylate is metabolised to salicylic acid and 1-hexanol, and 50 salicylic acid is the driver of any observed Hexyl Salicylate toxicity. The salicylic acid NOAELsys 51 = 75 mg/kg bw/day. A salicylic acid equivalent SED can be calculated and compare","endpoint":"developmental toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":48,"route":"oral","species":"human","study_id":"sccs_o_281_noael_016"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=180; DOSE=28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).; EFFECT=sier. 28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 33 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 34 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this 35 dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. 36 With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, 37 growth and behaviour were seen at the top dose. 38 39 An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). 40 Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 41 to 15 of gestation. A standard dose volume of 5ml/kg bw was used. Each group was n=24 42 female rats. There were no effects of treatment seen in dams and there were no embryotoxic 43 or teratogenic effects seen u; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995).","duration":"","effect":"sier. 28 29 Cyclohexyl Salicylate 30 31 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in 32 Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 33 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 34 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this 35 dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. 36 With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, 37 growth and behaviour were seen at the top dose. 38 39 An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). 40 Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 41 to 15 of gestation. A standard dose volume of 5ml/kg bw was used. Each group was n=24 42 female rats. There were no effects of treatment seen in dams and there were no embryotoxic 43 or teratogenic effects seen u","endpoint":"developmental toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"180","page":36,"route":"","species":"rat","study_id":"sccs_o_281_noael_008"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=1127; DOSE=6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH...; EFFECT=SCCS/1658/23 Preliminary version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study report; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH...","duration":"sub-acute","effect":"SCCS/1658/23 Preliminary version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study report","endpoint":"repeated dose toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg","noael_value":"1127","page":35,"route":"oral","species":"rat","study_id":"sccs_o_281_noael_002"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=1127; DOSE=6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH...; EFFECT=version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study reported as b; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH...","duration":"sub-acute","effect":"version Opinion on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) _________________________________________________________________________________ ________________________________________________________________________________________ 35 1 3.3.4.1 Repeated dose sub-acute and sub-chronic oral / dermal / inhalation toxicity 2 3 1-Hexanol 4 5 • Oral route 6 7 As summarised in the ECHA REACH dossier for 1-hexanol, a 13-week dietary study in rats 8 using hexan-1-ol reported a No Observed Adverse Effect Level (NOAEL) of 1127 mg/kg (study 9 reported as by Scientific Associates Inc., 1966). No adverse effects were noted at any of the 10 dose levels administered during the study. The results of this key study are supported by the 11 reliable (Klimisch score 2) 3-week feeding study in rats which reported a NOAEL of 12 approximately 1000 mg/kg bw/day (Moody and Reddy, 1978, 1982). In addition, a 13-week 13 study in dogs reported a NOAEL for 370 mg/kg bw/day for male dogs and 435 mg/kg bw/day 14 for female dogs (study reported as b","endpoint":"repeated dose toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg","noael_value":"1127","page":35,"route":"oral","species":"rat","study_id":"sccs_o_281_noael_003"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=0.1; DOSE=For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.; EFFECT=reproductive toxicity, the focus is on the more relevant metabolite salicylic acid data. The 14 Point of Departure for salicylic acid, as summarised by the SCCS conclusion in their 2018 15 Opinion, is the following: 16 17 SCCS agrees with RAC that salicylic acid is a developmental toxicant. Harmonised 18 classification of salicylic acid was recently published in Regulation 2018/1480 and is classified 19 as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 21 The developmental effects observed in this study are the most sensitive effects after repeated 22 exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) 23 and is also supported by Tanaka et al. (1973b).’ 24 25 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 26 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 27 28 This POD f; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al.","duration":"developmental","effect":"reproductive toxicity, the focus is on the more relevant metabolite salicylic acid data. The 14 Point of Departure for salicylic acid, as summarised by the SCCS conclusion in their 2018 15 Opinion, is the following: 16 17 SCCS agrees with RAC that salicylic acid is a developmental toxicant. Harmonised 18 classification of salicylic acid was recently published in Regulation 2018/1480 and is classified 19 as Repr. 2 (H361d Suspected of damaging the unborn child). For MoS calculation, SCCS uses 20 the developmental NOAEL of 0.1% (75 mg/kg bw/day) derived from Tanaka et al. (1973a). 21 The developmental effects observed in this study are the most sensitive effects after repeated 22 exposure to salicylic acid. This is also in agreement with the previous SCCNFP Opinion (2002) 23 and is also supported by Tanaka et al. (1973b).’ 24 25 In addition, due to the evidence for high (100%) oral bioavailability in humans, the oral NOAEL 26 of 75 mg/kg bw/day is defined as systemic NOAEL (NOAELsys) by SCCS for salicylic acid. 27 28 This POD f","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"%","noael_value":"0.1","page":37,"route":"oral","species":"human","study_id":"sccs_o_281_noael_009"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=29; DOSE=The 28 POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 29 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic 30 effects, in the Tanaka et al.; EFFECT=ate itself is not regarded as the main toxicant, 22 but rather salicylic acid as the chief hydrolysis product via all routes of exposure, it is possible 23 to perform a cosmetic safety evaluation for Hexyl Salicylate using the study by Tanaka et al. 24 1973 (from the reproductive/developmental data shown in section 3.4.5) for its principal 25 primary metabolite, salicylic acid. 26 27 Salicylic acid was reviewed recently by the SCCS in its Opinion from December 2023. The 28 POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 29 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic 30 effects, in the Tanaka et al. 1973 study. 31 32 A value for skin penetration of 13.4% (mean (3.04 +1SD) x a correction factor of 3) has been 33 used in all calculations of systemic exposure dose for dermally applied products (see section 34 3.2.2). 35 • MoS for Adults 36 37 Based on the exposure information in section 3.2, the Margins of Safety for consumer 38 exposures to Hexyl Salicylate in 18 cosmetic; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"The 28 POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 29 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic 30 effects, in the Tanaka et al.","duration":"developmental","effect":"ate itself is not regarded as the main toxicant, 22 but rather salicylic acid as the chief hydrolysis product via all routes of exposure, it is possible 23 to perform a cosmetic safety evaluation for Hexyl Salicylate using the study by Tanaka et al. 24 1973 (from the reproductive/developmental data shown in section 3.4.5) for its principal 25 primary metabolite, salicylic acid. 26 27 Salicylic acid was reviewed recently by the SCCS in its Opinion from December 2023. The 28 POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 29 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic 30 effects, in the Tanaka et al. 1973 study. 31 32 A value for skin penetration of 13.4% (mean (3.04 +1SD) x a correction factor of 3) has been 33 used in all calculations of systemic exposure dose for dermally applied products (see section 34 3.2.2). 35 • MoS for Adults 36 37 Based on the exposure information in section 3.2, the Margins of Safety for consumer 38 exposures to Hexyl Salicylate in 18 cosmetic","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg/day","noael_value":"29","page":45,"route":"","species":"rat","study_id":"sccs_o_281_noael_012"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=29; DOSE=The 28 POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 29 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic 30 effects, in the Tanaka et al.; EFFECT=main toxicant, 22 but rather salicylic acid as the chief hydrolysis product via all routes of exposure, it is possible 23 to perform a cosmetic safety evaluation for Hexyl Salicylate using the study by Tanaka et al. 24 1973 (from the reproductive/developmental data shown in section 3.4.5) for its principal 25 primary metabolite, salicylic acid. 26 27 Salicylic acid was reviewed recently by the SCCS in its Opinion from December 2023. The 28 POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 29 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic 30 effects, in the Tanaka et al. 1973 study. 31 32 A value for skin penetration of 13.4% (mean (3.04 +1SD) x a correction factor of 3) has been 33 used in all calculations of systemic exposure dose for dermally applied products (see section 34 3.2.2). 35 • MoS for Adults 36 37 Based on the exposure information in section 3.2, the Margins of Safety for consumer 38 exposures to Hexyl Salicylate in 18 cosmetic produc; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"The 28 POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 29 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic 30 effects, in the Tanaka et al.","duration":"developmental","effect":"main toxicant, 22 but rather salicylic acid as the chief hydrolysis product via all routes of exposure, it is possible 23 to perform a cosmetic safety evaluation for Hexyl Salicylate using the study by Tanaka et al. 24 1973 (from the reproductive/developmental data shown in section 3.4.5) for its principal 25 primary metabolite, salicylic acid. 26 27 Salicylic acid was reviewed recently by the SCCS in its Opinion from December 2023. The 28 POD for salicylic acid was selected as a no observed adverse effect level (NOAEL) of 75 29 mg/kg/day based upon the most sensitive observations in orally dosed rats, of teratogenic 30 effects, in the Tanaka et al. 1973 study. 31 32 A value for skin penetration of 13.4% (mean (3.04 +1SD) x a correction factor of 3) has been 33 used in all calculations of systemic exposure dose for dermally applied products (see section 34 3.2.2). 35 • MoS for Adults 36 37 Based on the exposure information in section 3.2, the Margins of Safety for consumer 38 exposures to Hexyl Salicylate in 18 cosmetic produc","endpoint":"reproductive toxicity","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"mg/kg/day","noael_value":"29","page":45,"route":"","species":"rat","study_id":"sccs_o_281_noael_013"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_281; REPORT_TITLE=SCIENTIFIC OPINION on Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6); OPINION_NUMBER=SCCS/1658/23; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=26 October 2023; VALUE_TEXT=35,433; EFFECT=pproximately 24 h and then 11 removed. A series of nine induction applications were completed over a period of three weeks. 12 A rest period of approximately 2 weeks followed the last induction. At the challenge phase, 13 patches were applied as in the induction phase and kept in place for 24 h, after which time 14 they were removed and the challenge sites were scored. The test sites were also scored at 15 48, 72 and 96 h post-patching. No sensitisation reactions were observed (RIFM (Harrison), 16 2004). The HRIPT NOEL was therefore 35,433 μg/cm2. 17 18 Hexyl Salicylate has been classified as a Category 4 substance (infrequent cause of contact 19 allergy in relation to level of exposure) with regard to its human skin sensitisation potential 20 (Basketter et al., 2014). This classification by authors of the study is based on an analysis of 21 human data adapted from a number of published references. Substances in Category 4 are 22 rarely important clinical allergens, because they require considerable/prolonged exposure to 23 hig; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"","duration":"2 weeks","effect":"pproximately 24 h and then 11 removed. A series of nine induction applications were completed over a period of three weeks. 12 A rest period of approximately 2 weeks followed the last induction. At the challenge phase, 13 patches were applied as in the induction phase and kept in place for 24 h, after which time 14 they were removed and the challenge sites were scored. The test sites were also scored at 15 48, 72 and 96 h post-patching. No sensitisation reactions were observed (RIFM (Harrison), 16 2004). The HRIPT NOEL was therefore 35,433 μg/cm2. 17 18 Hexyl Salicylate has been classified as a Category 4 substance (infrequent cause of contact 19 allergy in relation to level of exposure) with regard to its human skin sensitisation potential 20 (Basketter et al., 2014). This classification by authors of the study is based on an analysis of 21 human data adapted from a number of published references. Substances in Category 4 are 22 rarely important clinical allergens, because they require considerable/prolonged exposure to 23 hig","endpoint":"sensitisation","ingredient":"codes ................................................ 9","loael_value":"","noael_unit":"μg/cm2","noael_value":"35,433","page":32,"route":"","species":"human","study_id":"sccs_o_281_noael_001"}

sccs_o_281.pdf

SOURCE_SUBDIR=sccs_o_290; REPORT_TITLE=ADDENDUM TO THE SCIENTIFIC OPINION; OPINION_NUMBER=SCCS/1668/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 25 October 2024; VALUE_TEXT=180; DOSE=late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl...; EFFECT=late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 to 15 of gestation. A standard dose volume of 5ml/kg bw was us; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl...","duration":"","effect":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 to 15 of gestation. A standard dose volume of 5ml/kg bw was us","endpoint":"","ingredient":"s through damaged skin. Also, Hexyl Salicylate is classified as a","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"180","page":35,"route":"","species":"rat","study_id":"sccs_o_290_noael_007"}

sccs_o_290.pdf

SOURCE_SUBDIR=sccs_o_290; REPORT_TITLE=ADDENDUM TO THE SCIENTIFIC OPINION; OPINION_NUMBER=SCCS/1668/24; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 25 October 2024; VALUE_TEXT=unclear:SCCS/1668/24 Final version CORRIGENDUM Addendum to the Scientific Opinion on Hexyl Salicylate SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 46 Table 13: MoS for children under 3 years for aggregate exposure at all age groups median bodyweight (EFSA 2012) (kg) SE D (µg/kg/d) SED SA equivalent (µg/kg/d) MoS for SA equivalents (NOAEL = 75000 µg/kg/d) Infants 0 - 0.5 yrs 4.8 149.4 93.7 801 Infants 0.5 - 1 yrs 8.7 145.5 91.3 822 Toddlers 1 - 3 yrs 11.6 162.4 101.8 736 SA: salicylic acid In light of the high value of the MoS, the SCCS considers that Hexyl Salicylate is safe for children below 3 years, if used only in the products included in the aggregate exposure assessment at the presented maximum concentrations. 3.5 DISCUSSION Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) is the INCI name of ‘hexyl 2- hydroxybenzoate’, an ingredient wit; EFFECT=SCCS/1668/24 Final version CORRIGENDUM Addendum to the Scientific Opinion on Hexyl Salicylate SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 46 Table 13: MoS for children under 3 years for aggregate exposure at all age groups median bodyweight (EFSA 2012) (kg) SE D (µg/kg/d) SED SA equivalent (µg/kg/d) MoS for SA equivalents (NOAEL = 75000 µg/kg/d) Infants 0 - 0.5 yrs 4.8 149.4 93.7 801 Infants 0.5 - 1 yrs 8.7 145.5 91.3 822 Toddlers 1 - 3 yrs 11.6 162.4 101.8 736 SA: salicylic acid In light of the high value of the MoS, the SCCS considers that Hexyl Salicylate is safe for children below 3 years, if used only in the products included in the aggregate exposure assessment at the presented maximum concentrations. 3.5 DISCUSSION Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) is the INCI name of ‘hexyl 2- hydroxybenzoate’, an ingredient wit; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"6259-76-3","citation":"","dose":"","duration":"3 years","effect":"SCCS/1668/24 Final version CORRIGENDUM Addendum to the Scientific Opinion on Hexyl Salicylate SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 46 Table 13: MoS for children under 3 years for aggregate exposure at all age groups median bodyweight (EFSA 2012) (kg) SE D (µg/kg/d) SED SA equivalent (µg/kg/d) MoS for SA equivalents (NOAEL = 75000 µg/kg/d) Infants 0 - 0.5 yrs 4.8 149.4 93.7 801 Infants 0.5 - 1 yrs 8.7 145.5 91.3 822 Toddlers 1 - 3 yrs 11.6 162.4 101.8 736 SA: salicylic acid In light of the high value of the MoS, the SCCS considers that Hexyl Salicylate is safe for children below 3 years, if used only in the products included in the aggregate exposure assessment at the presented maximum concentrations. 3.5 DISCUSSION Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) is the INCI name of ‘hexyl 2- hydroxybenzoate’, an ingredient wit","endpoint":"","ingredient":"s through damaged skin. Also, Hexyl Salicylate is classified as a","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1668/24 Final version CORRIGENDUM Addendum to the Scientific Opinion on Hexyl Salicylate SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 46 Table 13: MoS for children under 3 years for aggregate exposure at all age groups median bodyweight (EFSA 2012) (kg) SE D (µg/kg/d) SED SA equivalent (µg/kg/d) MoS for SA equivalents (NOAEL = 75000 µg/kg/d) Infants 0 - 0.5 yrs 4.8 149.4 93.7 801 Infants 0.5 - 1 yrs 8.7 145.5 91.3 822 Toddlers 1 - 3 yrs 11.6 162.4 101.8 736 SA: salicylic acid In light of the high value of the MoS, the SCCS considers that Hexyl Salicylate is safe for children below 3 years, if used only in the products included in the aggregate exposure assessment at the presented maximum concentrations. 3.5 DISCUSSION Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) is the INCI name of ‘hexyl 2- hydroxybenzoate’, an ingredient wit","page":46,"route":"","species":"","study_id":"sccs_o_290_noael_015"}

sccs_o_290.pdf

{"dose":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl...","effect":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 to 15 of gestation. A standard dose volume of 5ml/kg bw was us","page":35,"pdf":"sccs_o_290.pdf","row_type":"noael_study","study_id":"sccs_o_290_noael_007"}

sccs_o_290.pdf

{"dose":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl...","effect":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 to 15 of gestation. A standard dose volume of 5ml/kg bw was us","page":35,"pdf":"sccs_o_290.pdf","row_type":"noael_study","study_id":"sccs_o_290_noael_007"}

sccs_o_290.pdf

{"dose":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl...","effect":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 to 15 of gestation. A standard dose volume of 5ml/kg bw was us","page":35,"pdf":"sccs_o_290.pdf","row_type":"noael_study","study_id":"sccs_o_290_noael_007"}

sccs_o_290.pdf

{"dose":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl...","effect":"late SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 35 An OECD Guideline 415 one-generation reproduction toxicity study was performed to GLP in Wistar rats treated orally with Hexyl Salicylate (Schmidt, 1995). Dose levels were 60, 180 and 540 mg/kg bw/day in corn oil. Some general toxicity effects were seen in the F0 generation at the top dose, and a NOAEL could be determined at 180 mg/kg bw/day; this dose had no effects on reproduction. In males a NOAEL was defined as 540 mg/kg bw/day. With the F1-generation, a NOAEL of 180 mg/kg bw/day as effects on litter responses, survival, growth and behaviour were seen at the top dose. An embryotoxicity study (including teratogenicity) was performed to GLP (Pitterman, 1996). Dose levels were 0, 40, 120 and 360 mg/kg bw/day, dosed daily in arachidis oil from day 6 to 15 of gestation. A standard dose volume of 5ml/kg bw was us","page":35,"pdf":"sccs_o_290.pdf","row_type":"noael_study","study_id":"sccs_o_290_noael_007"}

sccs_o_290.pdf

{"effect":"SCCS/1668/24 Final version CORRIGENDUM Addendum to the Scientific Opinion on Hexyl Salicylate SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 46 Table 13: MoS for children under 3 years for aggregate exposure at all age groups median bodyweight (EFSA 2012) (kg) SE D (µg/kg/d) SED SA equivalent (µg/kg/d) MoS for SA equivalents (NOAEL = 75000 µg/kg/d) Infants 0 - 0.5 yrs 4.8 149.4 93.7 801 Infants 0.5 - 1 yrs 8.7 145.5 91.3 822 Toddlers 1 - 3 yrs 11.6 162.4 101.8 736 SA: salicylic acid In light of the high value of the MoS, the SCCS considers that Hexyl Salicylate is safe for children below 3 years, if used only in the products included in the aggregate exposure assessment at the presented maximum concentrations. 3.5 DISCUSSION Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) is the INCI name of ‘hexyl 2- hydroxybenzoate’, an ingredient wit","page":46,"pdf":"sccs_o_290.pdf","row_type":"noael_study","study_id":"sccs_o_290_noael_015"}

sccs_o_290.pdf

{"effect":"SCCS/1668/24 Final version CORRIGENDUM Addendum to the Scientific Opinion on Hexyl Salicylate SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 46 Table 13: MoS for children under 3 years for aggregate exposure at all age groups median bodyweight (EFSA 2012) (kg) SE D (µg/kg/d) SED SA equivalent (µg/kg/d) MoS for SA equivalents (NOAEL = 75000 µg/kg/d) Infants 0 - 0.5 yrs 4.8 149.4 93.7 801 Infants 0.5 - 1 yrs 8.7 145.5 91.3 822 Toddlers 1 - 3 yrs 11.6 162.4 101.8 736 SA: salicylic acid In light of the high value of the MoS, the SCCS considers that Hexyl Salicylate is safe for children below 3 years, if used only in the products included in the aggregate exposure assessment at the presented maximum concentrations. 3.5 DISCUSSION Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) is the INCI name of ‘hexyl 2- hydroxybenzoate’, an ingredient wit","page":46,"pdf":"sccs_o_290.pdf","row_type":"noael_study","study_id":"sccs_o_290_noael_015"}

sccs_o_290.pdf

{"effect":"SCCS/1668/24 Final version CORRIGENDUM Addendum to the Scientific Opinion on Hexyl Salicylate SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 46 Table 13: MoS for children under 3 years for aggregate exposure at all age groups median bodyweight (EFSA 2012) (kg) SE D (µg/kg/d) SED SA equivalent (µg/kg/d) MoS for SA equivalents (NOAEL = 75000 µg/kg/d) Infants 0 - 0.5 yrs 4.8 149.4 93.7 801 Infants 0.5 - 1 yrs 8.7 145.5 91.3 822 Toddlers 1 - 3 yrs 11.6 162.4 101.8 736 SA: salicylic acid In light of the high value of the MoS, the SCCS considers that Hexyl Salicylate is safe for children below 3 years, if used only in the products included in the aggregate exposure assessment at the presented maximum concentrations. 3.5 DISCUSSION Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) is the INCI name of ‘hexyl 2- hydroxybenzoate’, an ingredient wit","page":46,"pdf":"sccs_o_290.pdf","row_type":"noael_study","study_id":"sccs_o_290_noael_015"}

sccs_o_290.pdf

{"effect":"SCCS/1668/24 Final version CORRIGENDUM Addendum to the Scientific Opinion on Hexyl Salicylate SCCS/1658/23 – children exposure 0-3 y.o. _________________________________________________________________________________ ________________________________________________________________________________________ 46 Table 13: MoS for children under 3 years for aggregate exposure at all age groups median bodyweight (EFSA 2012) (kg) SE D (µg/kg/d) SED SA equivalent (µg/kg/d) MoS for SA equivalents (NOAEL = 75000 µg/kg/d) Infants 0 - 0.5 yrs 4.8 149.4 93.7 801 Infants 0.5 - 1 yrs 8.7 145.5 91.3 822 Toddlers 1 - 3 yrs 11.6 162.4 101.8 736 SA: salicylic acid In light of the high value of the MoS, the SCCS considers that Hexyl Salicylate is safe for children below 3 years, if used only in the products included in the aggregate exposure assessment at the presented maximum concentrations. 3.5 DISCUSSION Hexyl Salicylate (CAS/EC No. 6259-76-3/228-408-6) is the INCI name of ‘hexyl 2- hydroxybenzoate’, an ingredient wit","page":46,"pdf":"sccs_o_290.pdf","row_type":"noael_study","study_id":"sccs_o_290_noael_015"}

sccs_o_290.pdf