Screening for Endocrine Bioactivity Potential of Tobacco Product Chemicals Including Flavor Chemicals

Adolescence and pregnancy involve elevated levels of hormones (e.g., estrogen, androgen) during which exposure to endocrine disruptors could have long-term developmental and reproductive toxicity (DART) effects. Therefore, the use prevalence and abuse liability of electronic nicotine delivery systems (ENDS) among adolescents and youth, and during pregnancy, raises concerns about possible exposure to endocrine disruptors. In addition, endocrine disruptors have adverse effects on wildlife and environmental health. While many studies focus on carcinogenicity and mutagenicity of tobacco products, research efforts screening chemicals in tobacco products for endocrine disruption potential are few. In this study, we curated 5179 chemicals in tobacco and tobacco smoke, 2803 flavor chemicals, and 156 e-liquid chemicals from literature or openly available databases. We screened the chemicals for endocrine bioactivity using new approach methodologies (NAMs) developed through US Environmental Protection Agency's Endocrine Disruptor Screening Program. The specific NAMs, estrogenic and androgenic pathway models, identified 137 tobacco chemicals, 34 flavor chemicals, and three e-liquid chemicals (Veratraldehyde, (2E)-3-Phenylprop-2-enal, and 2'-Acetonaphthone) as "active," indicating potential endocrine bioactivity. Further, among the tobacco chemicals with endocrine bioactivity potential, 48 were environmentally persistent, 29 bioaccumulative, and 19 both persistent and bioaccumulative. Our findings document many chemicals in tobacco products with potential endocrine bioactivity, which raises concerns for both human and environmental health. These results also underscore the importance of DART potential of tobacco products and flavors. Overall, our study characterizes the endocrine bioactivity potential of tobacco and flavor chemicals and provides a list of chemicals to consider in future ecological and health risk assessments.