G. Ritacco

RIFM fragrance ingredient safety assessment, ethyl anthranilate, CAS registry number 87-25-2

a Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA b Department of Dermatology, Member RIFM Expert Panel, Columbia University Medical Center, 161 Fort Washington Ave., New York, NY 10032, USA c Department of Occupational & Environmental Dermatology, Member RIFM Expert Panel, Malmo University Hospital, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d Member RIFM Expert Panel, University of Nebraska Lincoln, 230 Whittier Research Center, Lincoln, NE 68583-0857, USA e Department of Pathology, School of Veterinary Medicine and Animal Science, Member RIFM Expert Panel, University of Sao Paulo, Av. Prof. dr. Orlando Marques de Paiva, 87, Sao Paulo CEP 05508-900, Brazil f Department of Toxicology, Member RIFM Expert Panel, University of Wuerzburg, Versbacher Str. 9, Würzburg 97078, Germany g Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA h Department of Biochemistry, Center in Molecular Toxicology, Member RIFM Expert Panel, Vanderbilt University School of Medicine, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN 37232-0146, USA i Member RIFM Expert Panel, Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 6068507, Japan j Department of Comparative Medicine, College of Veterinary Medicine, Member RIFM Expert Panel, The University of Tennessee, 2407 River Dr., Knoxville, TN 37996-4500, USA k Member RIFM Expert Panel, Department of Pharmacology, College of Medicine, University of Arizona, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA

RIFM fragrance ingredient safety assessment, Linalool, CAS registry number 78-70-6.

a Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677 USA b Member RIFM Expert Panel, Department of Dermatology, Columbia University Medical Center, 161 Fort Washington Ave., New York, NY 10032, USA c Member RIFM Expert Panel, Department of Occupational & Environmental Dermatology, Malmo University Hospital, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d Member RIFM Expert Panel, University of Nebraska Lincoln, 230 Whittier Research Center, Lincoln, NE 68583-0857 USA e Member RIFM Expert Panel, School of Veterinary Medicine and Animal Science, Department of Pathology, University of Sao Paulo, Av. Prof. dr. Orlando Marques de Paiva, 87, Sao Paulo CEP 05508-900, Brazil f Member RIFM Expert Panel, Department of Toxicology, University of Wuerzburg, Versbacher Str. 9, Wurzburg 97078, Germany g Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239 USA h Member RIFM Expert Panel, Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN 37232-0146, USA i Member RIFM Expert Panel, Department of Dermatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 6068507, Japan j Member RIFM Expert Panel, College of Veterinary Medicine, Department of Comparative Medicine, The University of Tennessee, 2407 River Dr., Knoxville, TN 37996-4500, USA k Member RIFM Expert Panel, Department of Pharmacology, College of Medicine, University of Arizona, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA

RIFM fragrance ingredient safety assessment, benzyl isobutyrate, CAS Registry Number 103-28-6

RIFM fragrance ingredient safety assessment, benzyl isobutyrate, CAS Registry Number 103-28-6 A.M. Api a, , D. Belsito , S. Bhatia , M. Bruze , P. Calow , M.L. Dagli , W. Dekant , A.D. Fryer , L. Kromidas , S. La Cava , J.F. Lalko , A. Lapczynski , D.C. Liebler , V.T. Politano , G. Ritacco , D. Salvito , T.W. Schultz , J. Shen , I.G. Sipes , B. Wall , D.K. Wilcox a 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, Humphrey School of Public Affairs, University of Minnesota, 301 19th Avenue South, Minneapolis, MN 55455, USA e 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 f Member RIFM Expert Panel, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078 Würzburg, Germany g Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA h 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 i Member RIFM Expert Panel, The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN 37996-4500, USA j 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, borneol, CAS registry number 507-70-0.

a Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA b Member RIFM Expert Panel, Department of Dermatology, Columbia University Medical Center, 161 Fort Washington Ave., New York, NY 10032, USA c Member RIFM Expert Panel, Department of Occupational & Environmental Dermatology, Malmo University Hospital, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d Member RIFM Expert Panel, 230 Whittier Research Center, University of Nebraska Lincoln, Lincoln, NE 68583-0857, USA e Member RIFM Expert Panel, Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Av. Prof. dr. Orlando Marques de Paiva, 87, Sao Paulo CEP 05508-900, Brazil f Member RIFM Expert Panel, Department of Toxicology, University of Wuerzburg, Versbacher Str. 9, 97078 Würzburg, Germany g Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA h Member RIFM Expert Panel, Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN 37232-0146, USA i Member RIFM Expert Panel, Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 6068507, Japan j Member RIFM Expert Panel, Department of Comparative Medicine, College of Veterinary Medicine, The University of Tennessee, 2407 River Dr., Knoxville, TN 37996-4500, USA k Member RIFM Expert Panel, Department of Pharmacology, College of Medicine, University of Arizona, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA

RIFM fragrance ingredient safety assessment, methyl dihydrojasmonate, CAS registry number 24851-98-7

RIFM fragrance ingredient safety assessment, methyl dihydrojasmonate, CAS registry number 24851-98-7 A.M. Api a, D. Belsito b, S. Bhatia a, M. Bruze c, P. Calow d, M.L. Dagli e, W. Dekant f, A.D. Fryer g, L. Kromidas a,*, S. La Cava a, J.F. Lalko a, A. Lapczynski a, D.C. Liebler h, Y. Miyachi i, V.T. Politano a, G. Ritacco a, D. Salvito a, J. Shen a, T.W. Schultz j, I.G. Sipes k, B. Wall a, D.K. Wilcox a

RIFM fragrance ingredient safety assessment, Linalyl acetate, CAS Registry Number 115-95-7.

Please cite this article as: A.M. Api, D. Belsito, S. Bhatia, M. Bruze, P. Calow, M.L. Dagli, W. Dekant, A.D. Fryer, L. Kromidas, S. La Cava, J.F. Lalko, A. Lapczynski, D.C. Liebler, Y. Miyachi, V.T. Politano, G. Ritacco, D. Salvito, J. Shen, T.W. Schultz, I.G. Sipes, B. Wall, D.K. Wilcox, RIFM FRAGRANCE INGREDIENT SAFETY ASSESSMENT, Linalyl acetate, CAS Registry Number 115-95-7, Food and Chemical Toxicology (2015), http://dx.doi.org/doi: 10.1016/j.fct.2015.01.010.

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.