Comparison between endocrine activity assessed using ToxCast/Tox21 database and human plasma concentration of...

Sunscreen products are composed of ultraviolet (UV) filters and formulated to reduce exposure to sunlight thereby lessening skin damage. Concerns have been raised regarding the toxicity and potential endocrine disrupting (ED) effects of UV filters. The ToxCast/Tox21 program, that is, CompTox, is a high-throughput in vitro screening database of chemicals that identify adverse outcome pathways, key events, and ED potential of chemicals. Using the ToxCast/Tox21 database, octisalate, homosalate, octocrylene, oxybenzone, octinoxate, and avobenzone, 6 commonly used organic UV filters, were found to have been evaluated. These UV filters showed low potency in these bioassays with most activity detected above the range of the cytotoxic burst. The pathways that were most affected were the cell cycle and the nuclear receptor pathways. Most activity was observed in liver and kidney-based bioassays. These organic filters and their metabolites showed relatively weak ED activity when tested in bioassays measuring estrogen receptor (ER), androgen receptor (AR), thyroid receptor, and steroidogenesis activity. Except for oxybenzone, all activity in the endocrine assays occurred at concentrations greater than the cytotoxic burst. Moreover, except for oxybenzone, plasma concentrations (Cmax) measured in humans were at least 100× lower than bioactive (AC50/ACC) concentrations that produced a response in ToxCast/Tox21 assays. These data are consistent with in vivo animal/human studies showing weak or negligible endocrine activity. In sum, when considered as part of a weight-of-evidence assessment and compared with measured plasma concentrations, the results show these organic UV filters have low intrinsic biological activity and risk of toxicity including endocrine disruption in humans.