Analysis of in vitro profiling data of cosmetic ingredients within the Tox21 10K compound library for bioactivity and potential toxicity.

backgroundCosmetics are defined by the U.S. Food and Drug Administration (FDA) as "articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body…for cleansing, beautifying, promoting attractiveness, or altering the appearance". However, the safety of cosmetic ingredients is the responsibility of the manufacturer and exposure to some of these chemicals can result in unintentional harmful effects in humans. Thus, some states are banning specific chemicals, at the state legislation level, from being used in cosmetics, which includes known endocrine disruptors such as dibutyl phthalate, diethylhexyl phthalate, and per- and polyfluoroalkyl substances (PFAS). In this study, we aim to determine the toxicity pathways significantly affected by the cosmetic ingredients (both banned and non-banned), compared to the non-cosmetics compounds in the Tox21 10K library.

methodsThe Tox21 10K compound library (which includes 113 banned, 927 non-banned cosmetic ingredients and 8,185 non-cosmetic compounds) was previously screened against a panel of ~ 90 cell-based and biochemical assays. The hit rates (i.e., the percentage of compounds active in an assay) of the cosmetic and non-cosmetic compounds, as well as banned and non-banned compounds, in each Tox21 assay were compared using a Fisher's exact test, and a p-value < 0.05 was considered statistically significant.

resultsWe found that the evaluated cosmetic compounds were significantly more active in 11 antagonist mode assays and 23 agonist mode assays compared to the non-cosmetic compounds. The banned compounds were significantly more active in 7 antagonist mode and 6 agonist mode assays compared to the non-banned compounds. The targets of the antagonist assays included enzymes such as CYP2C19 and aromatase (CYP19A1), and the agonist assays included the Keap1/Nrf2 antioxidant response element pathway.

conclusionsIn the present study, we compared the bioactivity profiles of cosmetic ingredients and non-cosmetic compounds (not used in cosmetics), as well as the banned and non-banned cosmetic ingredients, across the Tox21 assays. The analyses revealed distinct molecular pathways for these chemicals which furthers our mechanistic understanding of cosmetics ingredient toxicity and may help direct the selection of cosmetic ingredients in the future with potentially less bioactivity. CLINICAL TRIAL NUMBER: Not applicable.