Dermal Sensitization Threshold Research Articles

RIFM fragrance ingredient safety assessment, 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone, CAS Registry number 61315-75-1

The existing information supports the use of this material as described in this safety assessment.4-(4-Methyl-3-penten-1-yl)-2(5H)-furanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is not mutagenic. The clastogenicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for the genotoxicity endpoint material, and the exposure to 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is below the TTC (0.0025 μg/kg/day). The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class III material, and the exposure to 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is not Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone was not able to be risk screened as there were no reported volumes of use (VoU) for either North America or Europe in the 2019 IFRA Survey.

RIFM fragrance ingredient safety assessment, 2,4,6-cycloheptatrien-1-one, 2-hydroxy-4-(1-methylethyl)-, CAS Registry Number 499-44-5

The existing information supports the use of this material as described in this safety assessment. This material has not been fully evaluated for photoallergenic potential.2,4,6-Cycloheptatrien-1-one, 2-hydroxy-4-(1-methylethyl)- was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that 2,4,6-cycloheptatrien-1-one, 2-hydroxy-4-(1-methylethyl)- is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to 2,4,6-cycloheptatrien-1-one, 2-hydroxy-4-(1-methylethyl)- is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. Based on data, 2,4,6-cycloheptatrien-1-one, 2-hydroxy-4-(1-methylethyl)- is a photoirritant but is not a concern under the current declared use levels. 2,4,6-Cycloheptatrien-1-one, 2-hydroxy-4-(1-methylethyl)- was not evaluated for photoallergenicity. The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 2,4,6-cycloheptatrien-1-one, 2-hydroxy-4-(1-methylethyl)- was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

Safety assessment of the use of recycled high-density polyethylene in cosmetics packaging based on in silico modeling migration of representative chemical contaminants for dermal sensitization and systemic endpoints

A safety assessment of recycled high-density polyethylene (rHDPE) in cosmetic packaging was performed based on guidelines published by the European Food Safety Authority (EFSA) on the use of recycled plastics for food packaging. EFSA guidelines require demonstration that the concentration of selected representative chemical contaminants in recycled plastic resulting from exposure from food is lower than the threshold of toxicological concern (TTC) for genotoxic substances of 0.0025 µg/kg bw/day. To investigate the highest concentration (Cmod) of representative chemical contaminants, that would not exceed the genotoxic TTC, when migrating from rHDPE packaging to foodstuffs, used as cosmetic formulation surrogates, we used mathematical modeling software (MIGRATEST®EXP). The Cmod values of representative chemical contaminants were then compared with the EFSA-reported residual concentration (Cres) of each contaminant in the rHDPE. For each of the cosmetic product/packaging combinations evaluated, we found that the modeled values were clearly lower for Cmod than Cres, i.e., the recycling process could effectively reduce potential contaminants of rHDPE to levels that would not result in daily consumer exposure from cosmetic use exceeding the genotoxic TTC. For skin sensitization, we modeled a worst-case scenario and assumed 100 % of each representative chemical contaminant migrates into the cosmetic formulation from rHDPE. We then calculated the consumer exposure level for each contaminant based on the dose per unit area and compared it with the dermal sensitization threshold (DST) for reactive materials, which is 64 µg/cm2. In each case, we demonstrated that the migration of each representative chemical contaminant from rHDPE into each cosmetic formulation was far below the DST, confirming that there is no appreciable risk of sensitization for protein-reactive chemicals. In conclusion, these data support the safe use of rHDPE in the packaging of cosmetic products for leave-on and rinse-off applications.

RIFM fragrance ingredient safety assessment, butyl lactate, CAS registry number 138-22-7

The existing information supports the use of this material as described in this safety assessment.Butyl lactate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog ethyl (L)-lactate (CAS # 687-47-8) show that butyl lactate is not expected to be genotoxic. Data on read-across materials butyl alcohol (CAS # 71-36-3) and lactic acid (CAS # 50-21-5) provide a calculated margin of exposure (MOE) > 100 for the repeated dose and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; butyl lactate is not expected to be phototoxic/photoallergenic. Data on butyl lactate provide a calculated MOE >100 for the local respiratory endpoint. The environmental endpoints were evaluated; butyl lactate was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, ethyl 2-methyl-4-pentenoate, CAS Registry Number 53399-81-8

The existing information supports the use of this material as described in this safety assessment.Ethyl 2-methyl-4-pentenoate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog methyl undec-10-enoate (CAS # 111-81-9) show that ethyl 2-methyl-4-pentenoate is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to ethyl 2-methyl-4-pentenoate is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; ethyl 2-methyl-4-pentenoate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; ethyl 2-methyl-4-pentenoate was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 5- and 6-decenoic acid, CAS Registry Number 72881-27-7

Summary: The existing information supports the use of this material as described in this safety assessment.5- and 6-Decenoic acid was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog oleic acid (CAS # 112-80-1) show that 5- and 6-decenoic acid is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to 5- and 6-decenoic acid is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 5- and 6-decenoic acid is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 5- and 6-decenoic acid was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, p-tolyl isobutyrate, CAS Registry Number 103-93-5

The existing information supports the use of this material as described in this safety assessment.p-Tolyl isobutyrate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analogs ethyl p-tolyl carbonate (CAS # 22,719-81-9) and p-tolyl acetate (CAS # 140-39-6) show that p-tolyl isobutyrate is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to p-tolyl isobutyrate is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; p-tolyl isobutyrate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; p-tolyl isobutyrate was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 4,5,6,7,8,9,10,11,12,13-decahydrocyclododecaoxazole, CAS Registry Number 38303-23-0

The existing information supports the use of this material as described in this safety assessment.4,5,6,7,8,9,10,11,12,13-Decahydrocyclododecaoxazole was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 4,5,6,7,8,9,10,11,12,13-decahydrocyclododecaoxazole is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to 4,5,6,7,8,9,10,11,12,13-decahydrocyclododecaoxazole is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 4,5,6,7,8,9,10,11,12,13-decahydrocyclododecaoxazole is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 4,5,6,7,8,9,10,11,12,13-decahydrocyclododecaoxazole was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 3,7-dimethyl-1,3,6-octatriene, CAS registry number 13877-91-3

The existing information supports the use of this material as described in this safety assessment. 3,7-Dimethyl-1,3,6-octatriene was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from 3,7-dimethyl-1,3,6-octatriene and read-across analog myrcene (β-myrcene; CAS # 123-35-3) show that 3,7-dimethyl-1,3,6-octatriene is not expected to be genotoxic and provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity and developmental and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 μg/cm 2 ); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 3,7-dimethyl-1,3,6- octatriene is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to 3,7-dimethyl-1,3,6-octatriene is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 3,7-dimethyl-1,3,6- octatriene was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental oncentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, glyceryl monooleate, CAS Registry Number 111-03-5

The existing information supports the use of this material as described in this safety assessment.Glyceryl monooleate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that glyceryl monooleate is not genotoxic. Data on glyceryl monooleate provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; glyceryl monooleate is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to glyceryl monooleate is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; glyceryl monooleate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 2-mercaptopropionic acid, CAS Registry Number 79-42-5

The existing information supports the use of this material as described in this safety assessment. 2-Mercaptopropionic acid was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 2-mercaptopropionic acid is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to 2-mercaptopropionic acid is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2-mercaptopropionic acid is not expected to be phototoxic/photoallergenic. For the hazard assessment based on the screening data, 2-mercaptopropionic acid is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 2-mercaptopropionic acid was not able to be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.

RIFM fragrance ingredient safety assessment, 3,4,4a,5,8,8a(Or 3,4,4a,7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran, CAS Registry Number 72429-08-4

The existing information supports the use of this material as described in this safety assessment. 3,4,4a,5,8,8a (Or 3,4,4a,7,8,8a)-Hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 3,4,4a, 5,8,8a (Or 3,4,4a, 7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to 3,4,4a, 5,8,8a (Or 3,4,4a, 7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 3,4,4a, 5,8,8a (Or 3,4,4a,7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 3,4,4a, 5,8,8a (Or 3,4,4a, 7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 2-cyclohexylcyclohexanone, CAS Registry Number 90-42-6

Summary: The existing information supports the use of this material as described in this safety assessment.2-Cyclohexylcyclohexanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data and read-across to 2-tert-butylcyclohexanone (CAS # 1728-46-7) show that 2-cyclohexylcyclohexanone is not expected to be genotoxic. Data on read-across material 2-sec-butylcyclohexanone (CAS # 14765-30-1) provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; 2-cyclohexylcyclohexanone is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class II material, and the exposure to 2-cyclohexylcyclohexanone is below the TTC (0.47 mg/day). The environmental endpoints were evaluated; 2-cyclohexylcyclohexanone was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 2-thiophenecarboxylic acid, ethyl ester, CAS Registry Number 2810-04-0

The existing information supports the use of this material as described in this safety assessment. 2-Thiophenecarboxylic acid, ethyl ester was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 2-thiophenecarboxylic acid, ethyl ester is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to 2-thiophenecarboxylic acid, ethyl ester is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; 2-thiophenecarboxylic acid, ethyl ester is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 2-thiophenecarboxylic acid, ethyl ester was found not to be PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.

RIFM fragrance ingredient safety assessment, dodecane, CAS Registry Number 112-40-3

Dodecane was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog nonane (CAS # 111-84-2) show that dodecane is not expected to be genotoxic. Data on read-across analog undecane (CAS # 1120-21-4) provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/vis) spectra; dodecane is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to dodecane is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; dodecane was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 2-methyl-4-(camphenyl-8)-cyclohexanone, CAS Registry Number 68901-22-4

2-Methyl-4-(camphenyl-8)-cyclohexanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 2-methyl-4-(camphenyl-8)-cyclohexanone is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to 2-methyl-4-(camphenyl-8)-cyclohexanone is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2-methyl-4-(camphenyl-8)-cyclohexanone is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 2-methyl-4-(camphenyl-8)-cyclohexanone was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, undecane, CAS Registry Number 1120-21-4

The existing information supports the use of this material as described in this safety assessment. Undecane was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog nonane (CAS # 111-84-2) show that undecane is not expected to be genotoxic. Data on undecane provide a calculated Margin of Exposure (MOE) >100 for the repeated dose and reproductive toxicity endpoints. Based on existing data and the application of the Dermal Sensitization Threshold (DST), undecane does not present a safety concern for skin sensitization under the current, declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; undecane is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to undecane is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; undecane was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC [Predicted Environmental Concentration/Predicted No Effect Concentration]), are <1.

RIFM fragrance ingredient safety assessment, 2-decanone, CAS Registry Number 693-54-9

The existing information supports the use of this material as described in this safety assessment.2-Decanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 2-heptanone (CAS # 110-43-0) show that 2-decanone is not expected to be genotoxic. Data on read-across analog 2-heptanone (CAS # 110-43-0) provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2-decanone is not expected to be phototoxic/photoallergenic. For the local respiratory endpoint, a calculated MOE >100 was provided by the read-across analog 4-methyl-2-pentanone (CAS # 108-10-1). The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 2-decanone is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 2-decanone was not able to be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.

Application of the dermal sensitization threshold concept to chemicals classified as high potency category for skin sensitization assessment of ingredients for consumer products

Skin sensitization evaluation is a key part of the safety assessment of ingredients in consumer products, which may have skin sensitizing potential. The dermal sensitization threshold (DST) concept, which is based on the concept of the thresholds of toxicological concern, has been proposed for the risk assessment of chemicals to which skin exposure is very low level. There is negligible risk of skin sensitization if a skin exposure level for the substance of interest was below the reactive DST which would protect against 95% of protein-reactive chemicals. For the remaining 5%, the substance with the defined knowledge of chemical structure (i.e., High Potency Category (HPC) rules) needs to be excluded from the application. However, the DST value for HPC chemicals has not yet been proposed. In this study, we calculated the 95th percentile probabilities estimate from distributions of skin sensitization potency data and derived a novel DST for HPC chemicals (HPC DST) of 1.5 μg/cm2. This value presents a useful default approach for unidentified substances in ingredients considering, as a worst-case scenario, that the unidentified compound may be a potent skin sensitizer. Finally, we developed a novel risk assessment workflow incorporating the HPC DST along with the previously published DSTs.

RIFM fragrance ingredient safety assessment, furfuryl thioacetate, CAS Registry Number 13678-68-7

Furfuryl thioacetate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that furfuryl thioacetate is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to furfuryl thioacetate is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; furfuryl thioacetate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; furfuryl thioacetate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.