Associations of Benzotriazoles and Benzothiazoles with Estrogens and Androgens Among Pregnant Women: A Repeated Measurement Cohort Study

Abstract

Background: People are extensively exposed to benzotriazoles (BTRs) and benzothiazoles (BTHs) derivatives, two classes of heterocyclic aromatic chemical compounds. Limited evidence has indicated the potential estrogen and androgen-disrupting effect of BTRs. Methods: Based on a prospective cohort study, we included 459 pregnant women, who donated complete serial urine samples at each trimester and had measurement of 4 BTRs and 4 BTHs, 3 estrogens [estrone (E1), 17β-estradiol (E2), and estriol (E3)] as well as 2 androgens [dehydroepiandrosterone (DHEA) and testosterone (T)] in the urine. ∑BTRs and ∑BTHs were calculated as the sum of the respective BTRs and BTHs. Associations of repeatedly measured BTRs, BTHs, ∑BTRs, and ∑BTHs with estrogens and androgens and the cross-sectional associations were analyzed. Findings: Repeated measurement analysis and cross-sectional analysis consistently found the target BTRs and BTHs were positively associated with E2, E3, and T, while the trend of the associations with T and DHEA were inconsistent. The most prominent percent of change was observed in E3 [43·5% (95% confidential interval: 36·7%, 50·7%)] associated with tolyltriazole (TTR). Percent of changes in estrogens and androgens associated with ∑BTHs were higher than that associated with individual BTHs; however, this phenomenon was not observed in BTRs. Significant modification effect of fetal sex was observed on the associations with E1, E3, T, and DHEA, where the percent of changes were higher in pregnant women giving birth to a boy than a girl. Interpretation: The disturbed estrogens and androgens associated with BTRs and BTHs indicated their estrogen and androgen-disrupting effect. The significant modification effect of fetal sex highlighted the potential sex-specific health risks of BTRs and BTHs related to altered sex hormones. Funding Information: Ministry of Science and Technology of the People's Republic of China, Health commission of Hubei Province, and the Program for HUST Academic Frontier Youth Team. Declaration of Interests: The authors declare they have no actual or potential competing financial interests. Ethics Approval Statement: The protocols of this study have obtained approval from the ethics committees of Tongji Medical College, Huazhong University of Science and Technology and WWCMHC.