Metabolism and environmental degradation of pyrethroid insecticides produce compounds with endocrine activities

Pyrethroids are semisynthetic derivatives of the chrysanthemumic acids that have been developed as insecticides, and they are in widespread use. Consi derable information is available regarding the toxicity, metabolism, and en vironmental degradation of pyrethroids, but almost nothing is known about t heir interactions with hormone receptors. In this study, seven commercial p yrethroids as well as products of metabolism and environmental degradation of permethrin were tested for steroid activity (both as agonist and as anta gonist) in recombinant yeasts expressing the human estrogen and human andro gen receptors. Pyrethroid insecticides had steroid receptor-binding activit y. Fenpropathrin and permethrin both acted as weak estrogen agonists. Allet hrin, bioallethrin, and expermethrin had antiestrogenic activity with poten cies between 1,000-fold (bioallethrin) and 10,000-fold (allethrin) less tha n the established antiestrogen 4-OH-tamoxifen. Six of the seven pyrethroids tested had antiandrogenic activity (the most active, bioallethrin, was 70- fold less potent than flutamide). These activities, however, are believed t o result either from contaminants/degradation products in the parent compou nds or from metabolism of the parent compounds into active metabolites by t he yeast. Three derivatives of permethrin all interacted with sex steroid h ormone receptors, Three-phenoxybenzyl alcohol had both estrogenic and antia ndrogenic activity, with potencies more than 100-fold greater than that of the parent compound, permethrin. Three-phenoxybenzoic acid and the cyclopro pane acid derivative both had antiestrogenic activity, with approximately 1 00-fold and 1,000-fold lower potencies than 4-OH-tamoxifen, respectively. T he data presented here highlight that an understanding of the metabolism an d environmental degradation of chemicals is essential for assessing the pot ential of chemicals to have endocrine-modulating effects.