Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 3-amino-1,2,4-triazole based on the Organization for Economic Co-operation and Development draft protocols.
We performed a uterotrophic assay, the Hershberger assay, and the 28-day repeated-dose toxicity study (enhanced OECD test guideline no. 407) of 3-amino-1,2,4-triazole based on the OECD draft protocols. In the uterotrophic assay, female SD rats were subcutaneously injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3 days from postnatal day 20 to day 22, and no changes were observed. In the Hershberger assay, the test chemical was orally administered at doses of 0, 40, 200, and 1,000 mg/kg/day to castrated male Wistar rats for 10 consecutive days beginning on postnatal day 56, and no androgen agonistic and antagonistic changes were observed. Alternatively, when the test chemical was orally administered at doses 0, 5, 25, and 125 mg/kg/day for at least 28 days in the subacute oral toxicity study, thyroid follicular epithelial cell hypertrophy with increased thyroid weights was detected in the male and female rats in 25 and/or 125 mg/kg groups, and hypertrophy of the anterior pituitary cells with increased pituitary weights in male and female rats was also observed in the 125 mg/kg group. Furthermore, serum T3 and T4 values decreased and serum TSH values increased in male and female rats in the 125 mg/kg group. Therefore, 3-amino-1,2,4-triazole was concluded to have anti-thyroid acting as endocrine-mediated effects, but no estrogenic or androgenic effects. In addition, decreased body weight, and abnormal biochemical parameters attributed to thyroid, liver or kidney dysfunction were observed in male and female rats in the 25 and/or 125 mg/kg groups.
Umano
Takaaki
T
Chemicals Evaluation and Research Institute, Bunkyo-ku, Tokyo, Japan. umano-takaaki@ceri.jp
Shiraishi
Keiji
K
Minobe
Yasushi
Y
Yamasaki
Kanji
K
D000284:Administration, Oral; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D001681:Biological Assay; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D017408:Guidelines as Topic; D007279:Injections, Subcutaneous; D008297:Male; D009919:Orchiectomy; D009929:Organ Size; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D023382:Toxicity Tests, Acute; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014284:Triiodothyronine / Q000097:blood; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects*
D013956:Antithyroid Agents; D052244:Endocrine Disruptors; D014230:Triazoles; D014284:Triiodothyronine; C056698:6-n-propyluracil; C045575:1,2,4-triazole; D014498:Uracil; D013972:Thyrotropin; D013974:Thyroxine