The role of P450 metabolism in the estrogenic activity of bifenthrin in fish

• Exposure to 4-hydroxy bifenthrin (metabolite) induces choriogenin in fish.
• Choriogenin is an estrogen-mediated protein.
• P450 metabolism increases the estrogenicity of bifenthrin.

Bifenthrin, a pyrethroid pesticide, is estrogenic in vivo in fishes. However, bifenthrin is documented to be anti-estrogenic in vitro, in the ER-CALUX (estrogen receptor) cell line. We investigated whether metabolite formation is the reason for this incongruity. We exposed Menidia beryllina (inland silversides) to 10 ng/l bifenthrin, 10 ng/l 4-hydroxy bifenthrin, and 10 ng/l bifenthrin with 25 μg/l piperonyl butoxide (PBO) – a P450 inhibitor. Metabolite-exposed juveniles had significantly higher estrogen-mediated protein levels (choriogenin) than bifenthrin/PBO-exposed, while bifenthrin alone was intermediate (not significantly different from either). This suggests that metabolites are the main contributors to bifenthrin's in vivo estrogenicity.