R. Parakhia

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, 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, isobornyl isovalerate, CAS registry number 7779-73-9.

This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization potential, as well as, environmental safety. Data from the suitable read across analog isobornyl acetate (CAS # 125-12-2) show that this material is not genotoxic, provided a MOE > 100 for the repeated dose, developmental and reproductive endpoints, and does not have skin sensitization potential. The local respiratory toxicity endpoint was completed using the TTC (threshold of Toxicological Concern) for a Cramer Class II material (0.47 mg/day). The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework.

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.

RIFM fragrance ingredient safety assessment, p-(2,2-dimethoxyethyl)toluene, CAS Registry Number 42866-91-1

RIFM fragrance ingredient safety assessment, p-(2,2-dimethoxyethyl) toluene, CAS Registry Number 42866-91-1 A.M. Api a, , D. Belsito , D. Botelho , D. Browne , M. Bruze , G.A. Burton Jr. , J. Buschmann , M.L. Dagli , M. Date , W. Dekant , C. Deodhar , M. Francis , A.D. Fryer , K. Joshi , S. La Cava , A. Lapczynski , D.C. Liebler , D. O’Brien , R. Parakhia , A. Patel , T.M. Penning , G. Ritacco , J. Romine , D. Salvito , T.W. Schultz , I.G. Sipes , Y. Thakkar , E.H. Theophilus , A.K. Tiethof , Y. Tokura , S. Tsang , J. Wahler 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, 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, 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 g Member RIFM Expert Panel, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078 Würzburg, Germany h Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA i 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 j 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 k Member RIFM Expert Panel, The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN 379964500, USA l 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 m Member RIFM Expert Panel, The Journal of Dermatological Science (JDS), Editor-in-Chief, Professor and Chairman, Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan

RIFM fragrance ingredient safety assessment, oxacyclohexadecane-2,13-dione, CAS Registry Number 38223-29-9

RIFM fragrance ingredient safety assessment, oxacyclohexadecane-2,13dione, CAS Registry Number 38223-29-9 A.M. Api, D. Belsito, D. Botelho, D. Browne, M. Bruze, G.A. Burton Jr., J. Buschmann, M.L. Dagli, M. Date, W. Dekant, C. Deodhar, M. Francis, A.D. Fryer, K. Joshi, S. La Cava, A. Lapczynski, D.C. Liebler, D. O’Brien, R. Parakhia, A. Patel, T.M. Penning, G. Ritacco, J. Romine, D. Salvito, T.W. Schultz, I.G. Sipes, Y. Thakkar, E.H. Theophilus, A.K. Tiethof, Y. Tokura, S. Tsang, J. Wahler

RIFM fragrance ingredient safety assessment, isodecyl alcohol, CAS registry number 25339-17-7

RIFM fragrance ingredient safety assessment, isodecyl alcohol, CAS registry number 25339-17-7 A.M. Api a, , D. Belsito , D. Botelho , D. Browne , M. Bruze , G.A. Burton Jr. , J. Buschmann , M.L. Dagli , M. Date , W. Dekant , C. Deodhar , A.D. Fryer , K. Joshi , S. La Cava , A. Lapczynski , D.C. Liebler , D. O’Brien , R. Parakhia , A. Patel , T.M. Penning , G. Ritacco , J. Romine , D. Salvito , T.W. Schultz , I.G. Sipes , Y. Thakkar , Y. Tokura , S. Tsang , J. Wahler a a Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA b Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave., New York, NY 10032, USA c Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d School of Natural Resources & Environment, University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI 58109, USA e Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625 Hannover, Germany f 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 g University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078 Würzburg, Germany h Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA i Vanderbilt University School of Medicine, Department of Biochemistry, Center in Molecular Toxicology, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN 37232-0146, USA j 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 k The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN 379964500, USA l Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA m Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan