Chlropyrifos-methyl shows anti-androgenic activity without estrogenic activity in rats.
Chlorpyrifos-methyl (CPM), an organophosphate insecticide, widely used for grain storage and agriculture, has been suspected as endocrine disrupter by a few in vitro studies. This study was performed to investigate the (anti-) estrogenicity and (anti-) androgenicity of CPM in vivo using immature rat uterotrophic assay and rat Hershberger assay. CPM with or without 17beta-estradiol were administered to 20 days old female rats to investigate its (anti-) estrogenic activity. Uterine and vaginal weight, uterine epithelial cell height were not affected by the treatment of CPM (2, 10, 50, 250 mg/kg). CPM 250 mg/kg potentiated relative vagina weight in 17beta-estradiol treated immature female rats without any changing of uterine weight. Relative liver weight was increased with decrease of body weight by CPM 250 mg/kg treatment. Uterine cell proliferation tested with bromodeoxyuridine labeling index was not observed in CPM treated rats. CPM with or without testosterone propionate were administered to castrated rat of 51 days old for 10 days to investigate the (anti-)androgenic activity,. The weight of relative and absolute androgen-dependent accessory sex organs; seminal vesicle with coagulating glands (SV/CG), ventral prostate gland (VP), glans penis (GP), levator ani plus bulbocarvernosus muscle (LABC) and Cowper's gland (CG,) were unchanged by the treatment of CPM alone. While CPM induced the increase of relative adrenal gland weight, CPM 50mg/kg decreased the weights of CV/CG, VP, CG and LABC without change of GP without changing of GP when it was treated with TP. In conclusion, CPM dose not show estrogenic and anti-estrogenic activity in immature female rats, but it represents anti-androgenic activity by inhibition of the TP-stimulated increase of the weight of accessory sex organs.
Kang
Hwan Goo
HG
National Veterinary Research and Quarantine Service, Division of Toxicology, 480, Anyang 6-dong, Anyang city 430-824, Republic of Korea.
Jeong
Sang Hee
SH
Cho
Joon Hyoung
JH
Kim
Dong Gyu
DG
Park
Jong Myung
JM
Cho
Myung Haing
MH
D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000633:toxicity*; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects* / Q000473:pathology; D005837:Genitalia, Male / Q000187:drug effects* / Q000473:pathology; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000494:pharmacology
D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D007306:Insecticides; D013739:Testosterone; D004958:Estradiol; D004390:Chlorpyrifos