• Toxicological Research
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• v.17
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• pp.313-317
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• 2001

The Ministry of Health and Welfare of Japan has set up six research groups concerning the endocrine disrupting chemicals. One of these projects was "A study on development of testing methodology for health effects due to exposure of environmental endocrine disruptors". In this paper, three topics are described. In OECD collaboration for pre-validation of uterotrophic assay, the most sensitive response to ethnyl estradiol was noted in the ovarectomized rats treated subcutaneously for 7 days. Secondly, it was suggested that changes of the serum $\alpha_{2u}$-globulin level may be a sensitive parameter for detecting the estrogenic activities of chemicals. Finally, development of the sexually dimorphic nucleus of preoptic area in the brain oj male rats was inhibited by the treatment with estrogenic chemicals, and their masculine behaviors and reproductive abilities were impaired after sexual maturation. In conclusion, these parameters are considered to be sensitive endpoints for testing estrogenic chemicals.chemicals.

• Toxicological Research
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• v.17 no.3
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• pp.203-213
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• 2001

We investigated the toxic effects of propylthiouracil (PTU) In Sprague-Dawley (SD) rats to develop and validate an enhanced Protocol for Test Guideline 407 as OECD Project. Twenty male and female SD rats,7 weeks old, were treated with PTU in corn oil at levels of 0, 0.1, 1 and 10 mg/kg/day for 4 weeks orally. Clinical observation, body weight changes, food uptake, water consumption, urinalysis, estrus cycle and sperm analysis, serum chemist교, autopsy findings and histopathological findings were evaluated in this study. No clinical signs and mortality were observed in the study. The body weights and food uptakes in the group treated with 10 mg/kg/day were reduced from 3 weeks after the initiation of the treatment. The levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4, 3,5,3',5'-tetraiodothyrosine) were also significantly decreased in the group treated with 10 mg/kg/day. Also, the relative and absolute organ weights of thymuses were decreased. Thyroid glands of rats in the group treated with PTU 10 mg/kg/day were bigger than those of rats in the control group. In the histopathological examination, diffuse hyperplasia and hypertrophy of thyroid follicular cells were observed in all treatment groups, leading to the reduction of lumen size and papillary enfolding of lining epithelium. The degree of lesion was increased in a dose-dependent manner. The results suggested that PTU would cause toxicity in thyroid gland and decrease the levels of T3 and T4 in SD rats. However there were no effects on the other organ including testis and uterus especially in spermatogenesis and estrus cycle. On the basis of the results, enhanced protocol for Test Guideline (TG) 407 may be sensitive and reliable to detect endocrine-active substances like PTU.