The potential endocrine disruption of pesticide transformation products (TPs): The blind spot of pesticide risk assessment

The ecological and health risk assessment of environmental pesticide residues have attracted ever-growing attention; however, their transformation products (TPs) have seldom been considered. Herein, we examined the endocrine-disrupting effects of 4 widely used pesticides as pyriproxyfen (Pyr), malathion (ML), benalaxyl (BX), and fenoxaprop-ethyl (FE), together with their 21 TPs through in vitro and in silico approaches, and found approximately 50% of the TPs exhibited stronger endocrine-disrupting effects than their corresponding parent compounds. Specifically, Pyr and 9 TPs (five TPs of Pyr, one of ML, one of BX, and two of FE) exhibited estrogen-disrupting effects, which were also confirmed by results of E-screen and pS2 expression assays, and molecular docking showed that certain hydroxylated TPs could well mimic the binding mode of estrogen with ER alpha. Meanwhile, two TPs of Pyr, ML and its TP demonstrated weak glucocorticoid antagonistic activities partially contributed by hydrogen bonds. We also discovered that in H295R cells, all the endocrine disruptors increased hormone secretion and the related gene expression levels. Conclusively, since an increasing number of pesticide TPs have been being detected in various environmental media, a more comprehensive understanding of the ecological risk of pesticide TPs is imperative for risk assessments more extensively and regulatory policy-making on pesticide restriction in the future.