Evaluation of Subchronic (13 Week), Reproductive, and in Vitro Genetic Toxicity Potential of 2-Ethylhexyl-2-cyano-3,3-diphenyl Acrylate (Octocrylene)

Use of 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Octocrylene)in commercial sunscreen products has increased considerablyin recent years. To support larger scale human exposure to thiscompound, additional toxicological information was needed inseveral key areas. The present studies evaluated subchronictoxicity, developmental toxicity, and in vitro genotoxic potentialof Octocrylene. In the subchronic study, male and female NewZealand white (NZW) rabbits treated topically with concentrationsof octocrylene up to 534 mg/kg/day for 13 weeks showed slightto moderate dose-dependent skin irritation that correlated positivelywith a mild depression in body weight gain. Lack of associatedhistopathologic or clinical hematology abnormalities suggestedthat the body weight effect probably reflected a nonspecificresponse to topical irritation. In percutaneous developmentaltoxicity studies, NZW does were treated topically with Octocryleneat levels up to 267 mg/kg/day on Days 6 through 18 of gestation.Body weight gain, food consumption, and all maternal, reproductive,and offspring parameters evaluated were comparable between Octocrylene-treatedand control animals. In the oral developmental toxicity assay,female CD-1 mice received oral doses of Octocrylene up to 1000mg/kg/day on Days 8–12 of gestation. No evidence of maternalor developmental toxicity was seen at any dose tested. Genotoxicitywas evaluated in vitro using the Chinese hamster ovary cellassay to assess clastogenicity and the mouse lymphoma cell assayto assess forward gene mutations. Octocrylene did not induceany significant increase in genotoxicity. This evaluation oftoxicological potential supports the use of Octocrylene as ahuman photoprotectant.     

The Interactive Toxicity of CHCl3 and BrCCl3 in Precision-Cut Rat Liver Slices

The interactive toxicity of two nontoxic concentrations of chloroform(CHCl₃and bromotricchloromethane (BrCCl₃ was examined in precision-cutrat liver slices. Liver slices were prepared from male Sprague-Dawleyrats (220–250 g) pretreated with phenobarbital for 4 days.Toxicants were administered 1 hr apart. Intracellular K⁺ levelswere similar to untreated controls in slices treated with 0.2mM CHCl₃ or 0.125 µ1 (0.25 mg, 1.26 µmol) BrCCl₃alone, indicating that these concentrations were nontoxic. However,addition of both toxicants, irrespective of order, resultedin a time-dependent loss of intracellular K⁺ which was significantat 9 hr following administration. This was interpreted as evidenceof synergistic toxicity. Cytochrome P450 loss was significantas early as 3 hr following exposure to BrCCl₃ alone or whenadded with CHCl₃ This loss may be attributed to BrCCl₃ suicideinactivation of cytochrome P450. Centrilobular hepatocytes maybe more susceptible to the interactive toxicity of CHCl₃ andBrCCl₃ Activity of enzymes found predominantly in this areawas significantly decreased in slices exposed to both toxicantsrelative to controls. Conversely, activity of enzymes foundpredominantly in the periportal region was similar to that ofuntreated and treated controls. Inter active toxicity of BrCCl₃and CHCl₃ was not a consequence of increased lipid peroxidationor depletion of slice glutathione content. Further studies needto be conducted to elucidate the mechanisms mediating the interactivetoxicity of BrCCl₃ and CHCl₃.