title: The fate of dermally applied [14C]d-limonene in rats and humans.
abstract: The fate of dermally applied [(14)C]d-limonene was evaluated in humans and Long-Evans rats. In rats, 5 mg/kg body weight of [(14)C]d-limonene applied dermally to the shaved back under occlusion, resulted in the absorption of approximately 12% of the dose. The absorbed d-limonene was completely metabolized and excreted rapidly, primarily from the urine (80%) with a small fraction (20%) excreted in the feces. There was no long-term retention of the test material in body tissues. In humans, following dermal application of 12 mg of [(14)C]d-limonene in ethanol (1 mL) to the back under nonocclusive conditions (for 1 h after application to allow the material to dry, thereafter under occlusion), only 0.16% of the dose was absorbed and the radioactivity was recovered from the urine. Radioactivity in human feces was below the limit of detection. These results indicate that under conditions of simulated use of fragrances and cosmetics, d-limonene has a low potential for dermal absorption and tissue accumulation, and the d-limonene that is absorbed is rapidly excreted in the urine. Based upon these findings and the knowledge that d-limonene possesses a low-systemic toxicity profile, it is reasonable to conclude that dermal exposure to d-limonene from fragrance and cosmetic applications is highly unlikely to result in any clinically significant human toxicity.
authors.affiliation: Research Institute for Fragrance Materials, Inc, Woodcliff Lake, NJ 07677, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Api
authors.forename: Gretchen
authors.initials: G
authors.lastname: Ritacco
authors.forename: David R
authors.initials: DR
authors.lastname: Hawkins
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D053138:Cyclohexenes / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D020405:Dermis / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000077222:Limonene; D008297:Male; D010476:Perfume; D051381:Rats; D020318:Rats, Long-Evans; D012869:Skin Absorption; D013729:Terpenes / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D053138:Cyclohexenes; D010476:Perfume; D013729:Terpenes; D000077222:Limonene