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Original Articles

Percutaneous Absorption, Disposition, and Exposure Assessment of Homosalate, a UV Filtering Agent, in Rats

, , , , , , , , , , & show all
Pages 202-213 | Received 25 Oct 2013, Accepted 28 Oct 2013, Published online: 20 Feb 2014
 

Abstract

Homosalate (HMS) is an ultraviolet (UV) filtering agent used in sunscreens and other cosmetics for skin protection purposes. Despite the widespread use of these products, absorption, disposition, and in vivo endocrine disrupting potential of HMS have not been characterized. Thus, the aim of this study was to examine the percutaneous absorption, disposition, and exposure assessment of HMS in rats. Initially, sunscreen preparations of petrolatum jelly, oily solution, lotion, and gel were prepared and evaluated for in vitro permeation of HMS across excised rat skin. Dermal permeability was greatest for gel, and this preparation was used in subsequent in vivo topical application investigations. After iv injection (0.5, 2, or 5 mg/kg), the pharmacokinetics of HMS was linear and was characterized by a large Vd ss (13.2–17 L/kg), high Cls (4.5–6.1 L/h/kg), and long t1/2 (6.1–8.4 h). After topical application of gel, the bioavailability of HMS was 5.4 ± 1.1 and 4.2 ± 0.6% for high and low doses (10 and 20 mg), respectively. Consistent with the prolonged absorption (T max 11.2 ± 1.8 and 12 ± 0 h for low and high doses, respectively), the terminal t 1/2 was longer after topical application (23.6–26.1 h) compared to iv injection. A population pharmacokinetic model was further developed to simultaneously fit the time courses of plasma concentrations and dermal content data after iv injection and topical application. Findings of this study may be useful to further examine the relationship between exposure and endocrine disrupting potential of HMS in risk assessment.

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