D. Botelho

RIFM fragrance ingredient safety assessment dihydro-β-terpinyl acetate, CAS Registry Number 26252-11-9

The use of this material under current conditions is supported by existing information. The material (dihydro-β-terpinyl acetate) was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data from the read across analog menthyl acetate (1α,2β,5α) (CAS # 89-48-5) show that dihydro-β- terpinyl acetate is not genotoxic nor does it have skin sensitization potential. The repeated dose, reproductive and local respiratory toxicity endpoints were completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (0.03, 0.03 mg/kg/day and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was completed based on UV spectra. The environmental endpoints were evaluated, dihydro-β-terpinyl acetate 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, 2-(p-menth-1-ene-10-yl)cyclopentanone, CAS Registry Number 95962-14-4

The use of this material under current conditions is supported by existing information. 2-(p-Menth-1-ene-10-yl)cyclopentanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that this material is not genotoxic and provided an MOE >100 for the repeated dose toxicity endpoint. Data show that there are no safety concerns for 2-(p-Menth-1-ene-10-yl)cyclopentanone for skin sensitization under the current declared levels of use. The developmental and reproductive as well as the local respiratory toxicity endpoints were completed using the Threshold of Toxicological Concern (TTC) for a Cramer Class II material (0.009 mg/kg/day and 0.47 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was completed based on UV spectra. The environmental endpoints were evaluated; 2-(p-menth-1-ene-10-yl)cyclopentanone 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, 1,1-diethoxyheptane, CAS Registry Number 688-82-4

The use of this material under current conditions is supported by existing information. 1,1-Diethoxyheptane was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from the read-across analog octanal dimethyl acetal (CAS # 10022-28-3) show that 1,1-diethoxyheptane is not expected to be genotoxic. Based on the application of the non-reactive DST, 1,1-diethoxyheptane does not present a concern for skin sensitization. The repeated dose, developmental and reproductive, and local respiratory toxicity endpoints were completed using the TTC for a Cramer Class I material (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was completed based on UV spectra. The environmental endpoints were evaluated; 1,1-diethoxyheptane 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, hexahydro-3H-benzofuran-2-one, CAS Registry Number 6051-03-2

Hexahydro-3H-benzofuran-2-one 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-oxaspiro[4.5]decan-2-one, 8-methyl- (CAS # 94201-19-1) show that hexahydro-3H-benzofuran-2-one is not expected to be genotoxic. The skin sensitization endpoint was completed using data from hexahydro-3H-benzofuran-2-one and the DST for non-reactive materials (900 μg/cm2); exposure is below the DST. Data on read-across analog 2(3H)-benzofuranone, hexahydro-3,6-dimethyl- (CAS # 92015-65-1) provide a calculated MOE >100 for the repeated dose toxicity endpoint. The reproductive and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class III material, and the exposure to hexahydro-3H-benzofuran-2-one is below the TTC (0.0015 mg/kg/day and 0.47 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; 1 hexahydro-3H-benzofuran-2-one is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 1 hexahydro-3H-benzofuran-2-one was found not to be a 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, ethyl 2-methyl-1,3-dioxolane-2-acetate, CAS Registry Number 6413-10-1

Ethyl 2-methyl-1,3-dioxolane-2-acetate (CAS # 6413-10-1) was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that ethyl 2-methyl-1,3-dioxolane-2-acetate is not genotoxic. Data from ethyl 2-methyl-1,3-dioxolane-2-acetate show that there are no safety concerns for skin sensitization under the current, declared levels of use. Data on ethyl 2-methyl-1,3-dioxolane-2-acetate provide a calculated MOE >100 for the repeated dose, developmental, and reproductive toxicity endpoints. The local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class III material, and the exposure to ethyl 2-methyl-1,3-dioxolane-2-acetate is below the TTC (0.47 mg/day). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; ethyl 2-methyl-1,3-dioxolane-2-acetate is not expected to be phototoxic/photoallergenic. For the environmental endpoints, ethyl 2-methyl-1,3-dioxolane-2-acetate is not PBT as per the IFRA Environmental Standards, and its risk quotients (i.e., PEC/PNEC) for the aquatic environment based on its current volume of use in Europe and North America are <1.

RIFM fragrance ingredient safety assessment, Methyl hexyl oxo cyclopentanone carboxylate, CAS Registry Number 37172-53-5

• Methyl hexyl oxo cyclopentanone carboxylate safety assessment based on RIFMs criteria.

RIFM fragrance ingredient safety assessment, benzoic acid, 2-[(1-oxopropyl)amino]-, methyl ester, CAS Registry Number 25628-84-6

• Benzoic acid, 2-[(1-oxopropyl)amino]-, methyl ester safety assessment based on RIFMs criteria.

RIFM fragrance ingredient safety assessment, benzenepropanenitrile, 4-ethyl-.α.,.α.-dimethyl, CAS Registry Number 134123-93-6

• Benzenepropanenitrile, 4-ethyl-α, α-dimethyl- safety assessment based on RIFMs criteria.

RIFM fragrance ingredient safety assessment, cuminyl nitrile, CAS Registry Number 13816-33-6

a Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA b Member RIFM Expert Panel, Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave., New York, NY 10032, USA c Member RIFM Expert Panel, Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d Member RIFM Expert Panel, School of Natural Resources & Environment, University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI 58109, USA e Member RIFM Expert Panel, Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625 Hannover, Germany f Member RIFM Expert Panel, Humphrey School of Public Affairs, University of Minnesota, 301 19th Avenue South, Minneapolis, MN 55455, USA g Member RIFM Expert Panel, University of Sao Paulo, School of Veterinary Medicine and Animal Science, Department of Pathology, Av. Prof. dr. Orlando Marques de Paiva, 87, Sao Paulo CEP 05508-900, Brazil h Member RIFM Expert Panel, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078 Würzburg, Germany i Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA j Member RIFM Expert Panel, Vanderbilt University School of Medicine, Department of Biochemistry, Center in Molecular Toxicology, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN 37232-0146, USA k Member of RIFM Expert Panel, University of Pennsylvania, Perelman School of Medicine, Center of Excellence in Environmental Toxicology, 1316 Biomedical Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, PA 19104-3083, USA l Member RIFM Expert Panel, The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN 379964500, USA m Member RIFM Expert Panel, Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA

RIFM fragrance ingredient safety assessment, acetic acid, C7-9-branched alkyl esters, C8-rich, CAS Registry Number 108419-32-5

The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data show that this material is not genotoxic. Data from the suitable read across analog isoamyl acetate (CAS# 123-92-2) show that this material does not have skin sensitization potential. The reproductive and local respiratory toxicity endpoints were completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (0.03 mg/kg/day and 1.4 mg/day, respectively). The repeated dose and developmental endpoint was completed using data on the target material, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework.