Potential estrogenic and antiandrogenic effects of permethrin in rats.
Many environmental chemicals including pesticides have been reported to possess hormonal activities, and thus are classified as endocrine disruptors. Permethrin, a synthetic pyrethroid insecticide, is used worldwide, which provides potential environmental exposure. However, relatively few studies have reported on hormonal activities, particularly estrogenic and androgenic activities of permethrin, and the results of these studies are in some respects contradictory. Therefore, this study investigated the potential estrogenic and androgenic activities of permethrin in vitro and in vivo. We conducted an uterine Calbindin-D9k (CaBP-9k) gene expression assay and an uterotrophic assay for estrogenic activity, and a Hershberger assay for androgenic activity. The CaBP-9k gene, one of the intracellular calcium binding proteins, is estrogen-responsive in the uterus. The rat uterotrophic and Hershberger assays are generally used as in vivo short-term screening assays for detecting the estrogenic and androgenic activities of chemicals, although these assays are still being validated by the Organization for Economic Cooperation and Development (OECD). Northern blot analysis showed the induction of uterine CaBP-9k mRNA level in response to permethrin as well as co-administration of permethrin with E2. In the uterotrophic assay using 18-day-old female rats, subcutaneous treatments with permethrin (10 to 800 mg/kg) for three days increased relative uterine wet weights, and E2-induced uterine weights. These effects were statistically significant at 800 and 200 mg/kg, respectively. Moreover, permethrin-induced uterine weights were inhibited by the co-administration of ICI 182,780, an antiestrogen. In the Hershberger assay, the administration of permethrin orally to testosterone propionate-treated castrated male rats led to statistically significant reductions in androgen-dependent sex accessory tissue (ventral prostate, seminal vesicles, levator ani and bulbocavernosus muscles, Cowper's gland and glans penis) weights at all doses tested (10, 50 and 100 mg/kg). These results suggest that permethrin might have estrogen-like effects on female rats, but antiandrogen-like effects on males.
Kim
Soon-Sun
SS
National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, Korea. sskeem@kfda.go.kr
Lee
Rhee-Da
RD
Lim
Kwon-Jo
KJ
Kwack
Seung-Jun
SJ
Rhee
Gyu-Seek
GS
Seok
Ji-Hyun
JH
Lee
Geun-Shik
GS
An
Beum-Soo
BS
Jeung
Eui-Bae
EB
Park
Kui-Lea
KL
D000367:Age Factors; D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D002030:Bulbourethral Glands / Q000033:anatomy & histology / Q000187:drug effects; D064026:Calbindins; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010413:Penis / Q000033:anatomy & histology / Q000187:drug effects; D026023:Permethrin / Q000494:pharmacology*; D010575:Pesticides / Q000494:pharmacology*; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D012669:Seminal Vesicles / Q000033:anatomy & histology / Q000187:drug effects; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects*
D000726:Androgen Antagonists; D064026:Calbindins; D010575:Pesticides; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; C576508:S100g protein, rat; D004958:Estradiol; D026023:Permethrin; D005485:Flutamide