Estrogenic and antiprogestagenic activities of pyrethroid insecticides

Many pesticides possess hormonal activity and have thus been classified as endocrine disruptors. Pyrethroids are commonly used insecticides worldwide, but little has been done to characterize their hormone agonist/antagonist potential. We tested four frequently encountered pyrethroids, fenvalerate, sumithrin, d-trans allethrin, and permethrin, for estrogen and progesterone agonist/antagonist activities using the Ishikawa Var-I human endometrial cancer cell line and the T47D human breast cancer cell line. Both cell lines produce alkaline phosphatase as an indicator of hormonal activity. Fenvalerate and sumithrin demonstrated significant estrogenicity; at concentrations of 10 microM, these compounds achieved maximal activities comparable to that of 10 nM 17alpha-ethynylestradiol in Ishikawa Var-I cells. None of the four compounds showed statistically significant estrogen antagonist activity or acted as progestins. However, fenvalerate and d-trans allethrin significantly antagonized the action of progesterone in T47D cells. Through these hormonal pathways, exposure to certain pyrethroids may contribute to reproductive dysfunction, developmental impairment, and cancer.