RIFM fragrance ingredient safety assessment, ethyl (E)hex-3-enoate, CAS registry number 26553-46-8.

The existing information supports the use of this material as described in this safety assessment. Ethyl (E)hex-3-enoate 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 3-hexenoate (CAS # 2396-78-3) show that ethyl (E)hex-3-enoate 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 (E)hex-3-enoate 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 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; ethyl (E)hex-3-enoate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; ethyl (E)hex-3-enoate 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-acetylthiazole, CAS Registry Number 24295-03-2.

The existing information supports the use of this material as described in this safety assessment. 2-Acetylthiazole was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 2-acetylthiazole is not genotoxic. 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 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 2-acetylthiazole is below the TTC (0.009 mg/kg/day, 0.009 mg/kg/day, and 0.47 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; 2-acetylthiazole is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated, 2-acetylthiazole 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, phenylethyl anthranilate, CAS Registry Number 133-18-6.

The existing information supports the use of this material as described in this safety assessment. Phenylethyl anthranilate was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from phenylethyl anthranilate and the read-across analog cinnamyl anthranilate (CAS # 87-29-6) show that phenylethyl anthranilate is not expected to be genotoxic. The skin sensitization endpoint was completed using the DST for non-reactive materials (900 µg/cm2); exposure is below the DST. The reproductive and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class II material, and the exposure to phenylethyl anthranilate is below the TTC (0.009 mg/kg/day and 0.47 mg/day, respectively). Data on read-across analogs phenethyl alcohol (CAS # 60-12-8) and anthranilic acid (CAS # 118-92-3) provide a calculated MOE >100 for the repeated dose and developmental toxicity endpoints. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; phenylethyl anthranilate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; phenylethyl anthranilate 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, 3-(4-methyl-3-pentenyl)-3-cyclohexene-1-carbonitrile, CAS registry number 68084-04-8.

The existing information supports the use of this material as described in this safety assessment. 3-(4-Methyl-3-pentenyl)-3-cyclohexene-1-carbonitrile was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 3-(4-methyl-3-pentenyl)-3-cyclohexene-1-carbonitrile is not genotoxic. Data show that there are no safety concerns for 3-(4-methyl-3-pentenyl)-3-cyclohexene-1-carbonitrile for skin sensitization under the current declared levels of use. 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-methyl-3-pentenyl)-3-cyclohexene-1-carbonitrile is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; 3-(4-methyl-3-pentenyl)-3-cyclohexene-1-carbonitrile is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated, 3-(4-methyl-3-pentenyl)-3-cyclohexene-1-carbonitrile 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 3-methylthiopropionate, CAS Registry Number 13327-56-5.

The existing information supports the use of this material as described in this safety assessment. Ethyl 3-methylthiopropionate 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 3-methylthiopropionate (CAS # 13532-18-8) show that ethyl 3-methylthiopropionate 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 3-methylthiopropionate 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 (UV) spectra; ethyl 3-methylthiopropionate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; ethyl 3-methylthiopropionate 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.