Bioaccumulation, metabolism and endocrine-reproductive effects of metolachlor and its S-enantiomer in adult zebrafish (Danio rerio)

Abstract

The aim of the present study was to evaluate the enantioselective bioaccumulation, metabolism, and toxic effects of metolachlor and S-metolachlor in zebrafish. Five-month-old zebrafish were exposed to metolachlor and S-metolachlor for 28 days, then transferred to clean water and purified for 7 days. In the uptake phase, S-metolachlor was preferentially accumulated at low concentrations, while metolachlor was preferentially accumulated at high concentrations. The two chemicals were metabolized by >70% in zebrafish on the first day and showed same metabolic process. At the accumulation endpoint, S-metolachlor had no significant inhibitory effect on the enzymes activities of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) and developmental indicators of zebrafish. However, 300 μg/L metolachlor significantly inhibited the enzymes activities of SOD, CAT and GST and affected the liver development. The preferential enrichment of metolachlor at the high concentration may be the reason for its higher toxicity to zebrafish. Further research demonstrated that metolachlor significantly altered the expression of hypothalamic-pituitary-gonadal (HPG) axis-related genes, including gnrh2, gnrh3, lhβ, 17βhsd and cyp19a, thereby reducing the levels of testosterone (T) in females and sex hormones (estradiol and testosterone) in males. S-metolachlor increased the levels of estradiol (E2) in females by altering the expression of HPG axis-related genes such as fshβ, cyp17, 17βhsd and cyp19a. The mechanism of metolachlor and S-metolachlor on the endocrine disrupting effects of zebrafish is different, which may be sex-specific. 7 days after transferring the exposed zebrafish to clean water, most of the enzymes activities, sex hormone levels and related gene expression levels returned to normal, which may be related to the rapid metabolism of the two chemicals.