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J Toxicol Environ Health A. 2014;77(4):202-13. doi: 10.1080/15287394.2013.861376.

Percutaneous absorption, disposition, and exposure assessment of homosalate, a UV filtering agent, in rats.

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1
a School of Pharmacy , Sungkyunkwan University , Suwon-si , Gyeonggi-do , Korea.

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 Cl(s) (4.5-6.1 L/h/kg), and long t½ (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 (Tmax 11.2 ± 1.8 and 12 ± 0 h for low and high doses, respectively), the terminal t½ 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.

PMID:
24555679
DOI:
10.1080/15287394.2013.861376
[Indexed for MEDLINE]

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