Comprehensive review of octocrylene toxicology data and human exposure assessment for personal care products

A comprehensive review was conducted of existing toxicity and consumer exposure data for the ultraviolet (UV) filter octocrylene (2-ethylhexyl-2-cyano-3,3-diphenylacrylate) as currently used in over-the-counter sunscreen formulations. Octocrylene has a long history of safe use, and there are sufficient <i>in vitro</i> studies, <i>in vivo</i> toxicity studies in animal models, and clinical data to characterize octocrylene's pharmacokinetics, pharmacodynamics, and potential toxicologic properties. Although no harmonized dermal absorption value was available, <i>in vitro</i> studies using human skin samples revealed very low percutaneous absorption (0.33% of the applied dose). There are no specific data on the distribution of octocrylene; however, there is some information on background levels of octocrylene and its metabolism, and it has limited presence in plasma and urine from human biomonitoring studies. Six tentative metabolites of octocrylene have been identified, although metabolite-specific toxicity profiles were not available. Octocrylene generally did not cause eye or skin irritation, skin sensitization, or phototoxicity, but dermal sensitization has been reported in some clinical case studies. Octocrylene is not acutely toxic. The no-observed-adverse-effect level (NOAEL) from a 90-day rat dietary toxicity study was 175 mg/kg/day, based on liver, thyroid, and pituitary effects at higher dose levels that produced hepatic enzyme induction. The NOAEL for parental systemic, reproductive, and developmental toxicity from an extended one-generation reproductive toxicity study in rats was 153/163 mg/kg/day (males/females). There was no evidence of octocrylene effects on neurodevelopment, immune tissues, or androgenic, estrogenic, or thyroid endpoints. Although there are no formal 2-year carcinogenicity studies for octocrylene, a 90-day subchronic dietary toxicity study in rats did not show an increase in hyperplasia of any tissue or evidence of cytotoxicity. Furthermore, octocrylene has not triggered any indications for genotoxicity either <i>in vitro</i> or <i>in vivo.</i> Together, these data indicate that carcinogenicity in humans is unlikely. In a mouse photocarcinogenicity study, octocrylene significantly reduced tumor number and tumor volume resulting from exposure to solar-simulated UV radiation. Based on the most health-protective rat NOAEL (153 mg/kg/day, for reproductive effects and general toxicity) and conservative assumptions for estimating the systemic exposure dose from the application of sunscreen products, margins of safety for octocrylene were greater than 100. Therefore, the available data show that octocrylene poses no human health risks when used in sunscreen products at concentrations up to 10%, which is consistent with existing global regulatory safety acceptance and approval of the ingredient.