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, 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, 6-nonenenitrile, (Z)- (9CI), CAS Registry Number 80639-54-9.

The existing information supports the use of this material as described in this safety assessment. 6-Nonenenitrile, (Z)- (9CI) was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 3-(cis-3-hexenyloxy)propanenitrile (CAS # 142653-61-0) show that 6-nonenenitrile, (Z)- (9CI) 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 III material, and the exposure to 6-nonenenitrile, (Z)- (9CI) is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). Data from read-across analog 3-(cis-3-hexenyloxy)propanenitrile (CAS # 142653-61-0) show that there are no safety concerns for 6-nonenenitrile, (Z)- (9CI) for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 6-nonenenitrile, (Z)- (9CI) is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 6-nonenenitrile, (Z)- (9CI) 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.

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, 1-heptanethiol, CAS Registry Number 1639-09-4.

1-Heptanethiol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 1-octanethiol (CAS # 111-88-6) show that 1-heptanethiol is not expected to be genotoxic and provide a calculated MOE >100 for the reproductive toxicity endpoint. Data on read-across analog dodecanethiol (CAS # 112-55-0) provide a calculated MOE >100 for the repeated dose toxicity endpoint. Data show that there are no safety concerns for 1-heptanethiol for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on UV/Vis spectra for read-across analog methyl mercaptan (CAS # 74-93-1); 1-heptanethiol is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the TTC for a Cramer Class I material; exposure is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 1-heptanethiol 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, 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, 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, 7,9-dimethylspiro[5.5]undecan-3-one, CAS Registry Number 83863-64-3.

The existing information supports the use of this material as described in this safety assessment. 7,9-Dimethylspiro[5.5]undecan-3-one was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 7,9-dimethylspiro[5.5]undecan-3-one 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 II material, and the exposure to 7,9-dimethylspiro[5.5]undecan-3-one is below the TTC (0.009 mg/kg/day, 0.009 mg/kg/day, and 0.47 mg/day, respectively). Based on the existing data and readacross material spiro[5.5]undec-8-en-1-one, 2,2,7,9-tetramethyl- (CAS # 502847-01-0), 7,9-dimethylspiro[5.5]undecan-3-one presents no concern for skin sensitization under the current, declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on data and ultraviolet (UV) spectra; 7,9-dimethylspiro[5.5]undecan-3-one is not phototoxic/photoallergenic. The environmental endpoints were evaluated; 7,9-dimethylspiro[5.5]undecan-3-one 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, 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, p-tolualdehyde, CAS Registry Number 104-87-0.

The existing information supports the use of this material as described in this safety assessment. p-Tolualdehyde was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, and environmental safety. Data from read-across analog benzaldehyde (CAS # 100-52-7) show that p-tolualdehyde is not expected to be genotoxic. Data from read-across analog cuminaldehyde (CAS # 122-03-2) provided p-tolualdehyde a No Expected Sensitization Induction Level (NESIL) of 1100 µg/cm2 for the skin sensitization endpoint. The repeated dose toxicity, developmental and reproductive toxicity, and local respiratory toxicity endpoints were completed using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to p-tolualdehyde is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on data from read-across analog 4-ethylbenzaldehyde (CAS # 4748-78-1); p-tolualdehyde is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; p-tolualdehyde 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 (ß-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 low-exposure fragrance ingredients safety assessment.

The existing information supports the use of these materials as described in this safety assessment. The 167 materials identified in this assessment were evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Target data, read-across analogs and TTC show that these materials are not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for their respective Cramer Classes (see Fig. 1 below) and the exposure to these materials is below the TTC. The skin sensitization endpoint was completed using the DST for non-reactive and reactive materials (900 µg/cm2 and 64 µg/cm2, respectively); exposures are below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; these materials are not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; the materials were found not to be PBT as per the IFRA Environmental Standards, and their risk quotients, based on their current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.

RIFM fragrance ingredient safety assessment, cyclohexanol, CAS Registry Number 108-93-0.

The existing information supports the use of this material as described in this safety assessment. Cyclohexanol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that cyclohexanol is not genotoxic. Data on cyclohexanol provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. Data show that there are no safety concerns for cyclohexanol for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; cyclohexanol 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 cyclohexanol is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; cyclohexanol 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, methyl-2,2-dimethyl-6-methylene-1-cyclohexanecarboxylate, CAS Registry Number 81752-87-6.

The existing information supports the use of this material as described in this safety assessment. Methyl-2,2-dimethyl-6-methylene-1-cyclohexanecarboxylate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that methyl-2,2-dimethyl-6-methylene-1-cyclohexanecarboxylate is not genotoxic. Data on methyl-2,2-dimethyl-6-methylene-1-cyclohexanecarboxylate provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity endpoint. The 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 methyl-2,2-dimethyl-6-methylene-1-cyclohexanecarboxylate is below the TTC (0.03 mg/kg/day and 1.4 mg/day, respectively). Data show that there are no safety concerns for methyl-2,2-dimethyl-6-methylene-1-yclohexanecarboxylate for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; methyl-2,2-dimethyl-6-methylene-1-cyclohexanecarboxylate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; methyl-2,2-dimethyl-6-methylene-1-cyclohexanecarboxylate 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, 3,4,4a,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.

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, 3-octanol, CAS Registry Number 589-98-0.

The existing information supports the use of this material as described in this safety assessment. 3-Octanol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 3-hexanol (CAS # 623-37-0) show that 3-octanol is not expected to be genotoxic. Data on 3-octanol provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity endpoint. Data on read-across analog 2-octanol (CAS # 123-96-6) provide a calculated MOE >100 for the reproductive toxicity endpoint and show that there are no safety concerns for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 3-octanol 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; exposure is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 3-octanol 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, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol, CAS Registry Number 526218-21-3.

The existing information supports the use of this material as described in this safety assessment. 1-(2-Methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not genotoxic. Data on 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity endpoint. The 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 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is below the TTC (0.0015 mg/kg/day and 0.47 mg/day, respectively). Data show that there are no safety concerns for 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 1-(2-methylprop-2-enoloxy)-2,2,4-trimethylpentan-3-ol 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.