Review A toxicologic and dermatologic assessment of salicylates when used as fragrance ingredients q The RIFM Expert Panel D. Belsito a , D. Bickers b , M. Bruze c , P. Calow d , H. Greim e , J.M. Hanifin f , A.E. Rogers g , J.H. Saurat h , I.G. Sipes i , H. Tagami j a University of Missouri (Kansas City), c/o American Dermatology Associates, LLC, 6333 Long Avenue, Third Floor, Shawnee, KS 66216, USA b Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Avenue, New York, NY 10032, USA c Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d Institut for Miliovurdering, Environmental Assessment Institute, Linne ´sgade 18, 1st floor, Copenhagen 1361 K, Denmark e Technical University of Munich, Institute for Toxicology & Environmental Hygiene, Hohenbachernstrasse 15-17, Freising-Weihenstephan D-85354, Germany f Oregon Health Sciences University, Department of Dermatology L468, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA g Boston University School of Medicine, Department of Pathology and Laboratory Medicine, 715 Albany Street, L-804, Boston, MA 02118-2526, USA h Hospital Cantonal Universitaire, Clinique et Policlinique de Dermatologie, 24, Rue Micheli-du-Crest, Geneve 14 1211, Switzerland i Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA j 3-27-1 Kaigamori, Aoba-ku, Sendai 981-0942, Japan Abstract An evaluation and review of a structurally related group of fragrance materials. Ó 2007 Published by Elsevier Ltd. Keywords: Safety; Review; Salicylates; Fragrance Contents 1. Chemical identity and exposure (Table 1).......................................................... S319 1.1. Estimated consumer exposure................................................................ S323 2. Absorption, distribution and metabolism, and potential for enzyme induction................................ S323 2.1. Absorption ............................................................................ S323 2.1.1. Percutaneous absorption (Tables 2–5) ................................................ S323 2.1.2. Oral absorption................................................................ S325 2.1.3. Inhalation absorption ........................................................... S326 2.2. Distribution and pharmacokinetics ........................................................... S326 2.3. Metabolism (Fig. 1) ...................................................................... S327 3. Toxicological studies ........................................................................ S329 3.1. Acute toxicity (Tables 6a–6c) ............................................................... S329 3.2. Subchronic toxicity (Table 7) ............................................................... S330 3.2.1. Dermal studies ................................................................ S330 0278-6915/$ - see front matter Ó 2007 Published by Elsevier Ltd. doi:10.1016/j.fct.2007.09.066 q All correspondence should be addressed to: A.M. Api, 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA. Tel.: +1 201 689 8089; fax: +1 201 689 8090. E-mail address: amapi@rifm.org www.elsevier.com/locate/foodchemtox Available online at www.sciencedirect.com Food and Chemical Toxicology 45 (2007) S318–S361