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

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.

The No-Observed-Adverse-Effect Level (NOAEL) of Baby Aloe Powder (BAP) for Nutraceutical Application Based Upon Toxicological Evaluation

“…With the NOAEL of >2g/kg bw, the uncertainty factor (UF) of 100, and {the modifying factor (MF) of 3, the RDA of BAP was calculated as >6.67 mg/kg bw/d (or >400 mg/60 kg adult/d)}. The determination process of NOAEL is critical for human risk assessment to promote public health (Bolt et al, 2012;Choi et al, 2010;Meng et al, 2012;Dahshan et al, 2013;Kim et al, 2014). These data suggest that BAP used in this study may be considered safe for use in food, pharmaceutical, and cosmetic applications.…”

Assessment of in Vitro Genotoxicity Effect of Homosalate in Cosmetics

“…HMS may be attributed to high affinity binding to the lipophilic components of the skin layers. HMS absorb into the systemic circulation from skin after topical application of the gel formulation in rats [8]. Schlumpf et al [10] also found residues of HMS in breast milk samples.…”

“…It is also reported that some skinabsorbed UV filters could result unknown systemic toxic effects [6]. However, recent studies have shown that organic UV filters in certain formulation -after absorption through the skin-have the potential of being metabolized and excreted [7,8]. Now that many organic UV filters are lipophilic, they can easily bioaccumulate and biomagnify in aquatic ecosytems, where their impact is a big concern.…”

Sunscreen and Suntan Preparations

“…Homosalate (HMS) is an UV filtering agent used in sunscreens and other cosmetics for skin protection purposes. It is a viscous or light yellow to slightly tan liquid or oil, derives from salicylic acid [70,71]. Salicylates are weak UVB absorbers and they are generally used in combination with other UV filters.…”