Repeated 28-day oral toxicity study of vinclozolin in rats based on the draft protocol for the "Enhanced OECD Test Guideline No. 407" to detect endocrine effects.
We performed a 28-day repeated-dose toxicity study of vinclozolin, a widely used fungicide, based on the draft protocol of the "Enhanced OECD Test Guideline 407" (Enhanced TG407) to investigate whether vinclozolin has endocrine-mediated properties according to this assay. Seven-week-old SD rats were administered with vinclozolin daily by oral gavage at dose rates of 0, 3.125, 12.5, 50 and 200 mg/kg/day for at least 28 days. The vinclozolin-treated male rats showed a reduction of epididymis and accessory sex organ weights and an alteration of hormonal patterns. A slight prolongation of the estrous cycle and changes in the estrogen/testosterone ratio and luteinizing hormone level were observed in vinclozolin-treated female rats. Thyroxin concentrations were decreased and thyroid-stimulating hormone concentrations were increased in both sexes; however, there were no compound-related microscopic lesions in the thyroid gland or changes in the thyroid weight. The endocrine-related effects of vinclozolin could be detected by the parameters examined in the present study based on the OECD protocol, suggesting the Enhanced TG407 protocol should be a suitable screening test for the detection of endocrine-mediated effects of chemicals.
Endocrine Toxicology Team, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul 122-704, Korea. jaehoshin@hanmir.com
Jae-Ho
JH
Shin
Hyun Ju
HJ
Moon
Tae Sung
TS
Kim
Il Hyun
IH
Kang
Ho Yeon
HY
Ki
Kwang Sik
KS
Choi
Soon Young
SY
Han
D000284:Administration, Oral; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000097:blood; D030762:Estrous Cycle / Q000097:blood / Q000187:drug effects; D005062:European Union; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D005837:Genitalia, Male / Q000187:drug effects* / Q000473:pathology; D017408:Guidelines as Topic; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010080:Oxazoles / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D018675:Toxicity Tests / Q000379:methods*
D000726:Androgen Antagonists; D004967:Estrogens; D005659:Fungicides, Industrial; D010080:Oxazoles; D013739:Testosterone; D007986:Luteinizing Hormone; D013972:Thyrotropin; C025643:vinclozolin; D013974:Thyroxine