Toxic effects of chloroacetanilides on the endocrine system (literature review)

This review article summarizes current knowledge on the endocrine-disrupting effects of chloroacetanilide herbicides – compounds widely employed in agriculture for the control of annual grasses and certain dicotyledonous weeds. Exposure to these xenobiotic has been associated with a range of adverse health outcomes in both adult and developing organisms. To assess their endocrine toxicity, the authors performed a comprehensive analysis of toxicological data retrieved from major international and national scientific databases, including FAO/WHO, EXTOXNET, EPA, EFSA, EMBASE, Global Health, Scopus, Web of Science, MedLine, PubMed, eLibrary, CyberLeninka, and Springer Nature Link.

The reviewed evidence indicates that chloroacetanilides exert multimodal effects on the endocrine system, targeting the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), and hypothalamic-pituitary-thyroid (HPT) axes. These compounds interfere with the synthesis of steroid and thyroid hormones through both direct interaction with hormone receptors and modulation of enzymes involved in hormone biosynthesis and metabolism. Specifically, dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion has been demonstrated, along with competitive binding of acetochlor, metolachlor, and their metabolites to androgen receptors. In addition, estrogenic activity has been observed, evidenced by the induction of vitellogenin synthesis and upregulation of aromatase (cyp19a1a) gene expression in aquatic species, suggesting disruption of endogenous estrogen regulation. With respect to the HPT axis, the primary effect is a reduction in thyroxine (T₄) levels, likely mediated through inhibition of type 2 deiodinase – the enzyme responsible for peripheral conversion of T₄ to triiodothyronine (T₃). Notably, these effects were most pronounced following exposure to S-enantiomers.

Authors’ contribution:
Sinitskaya T.A. – scientific supervision, study concept and design, editing;
Khamidulina Kh.Kh. – scientific consulting, editing;
Poroshin M.A. – material collection and writing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no obvious or potential conflicts of interest in connection with the publication of this article.

Funding. The study had no sponsorship.

Received: March 24, 2026 / Accepted: March 27, 2026 / Published: April 30, 2026

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