Uterotrophic assay Hershberger assay and subacut

Authors: Kanji Yamasaki Katusi Miyata Keiji Shiraishi Takako Muroi Nobuhiko Higashihara Hiroshi Oshima Yasushi Minobe

Publish Date: 2007/10/09

Volume: 82, Issue: 5, Pages: 301-311

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Abstract

We performed a uterotrophic assay the Hershberger assay and a 28day repeateddose toxicity study enhanced Organization for Economic Cooperation and Development OECD test guideline No 407 of 44′butylidenebis2tertbutyl5methylphenol and 3dibutylaminophenol based on the OECD draft protocols In the uterotrophic assay of 44′butylidenebis2tertbutyl5methylphenol female SD rats were subcutaneously injected with the chemical at doses of 0 100 300 and 1000 mg/kg on each of 3 days from postnatal day 20 to day 22 and no changes were observed In the Hershberger assay of 44′butylidenebis2tertbutyl5methylphenol the test chemical was orally administered to castrated male SD rats at doses of 0 50 200 and 1000 mg/kg/day for ten consecutive days beginning on postnatal day 56 and no changes were observed When this 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 an increase in thyroid weight was observed in the female rats in the 125 mg/kg group an increase in serum thyroidstimulating hormone TSH values in the male and female rats in the 125 mg/kg group and a decrease in serum T3 and T4 values in the male rats in the 125 mg/kg group and thyroid follicular epithelial cell hypertrophy was observed in some of the female rats in the 125 mg/kg group These findings were concluded to be the result of endocrinemediated effects of the chemical on thyroid function In addition increased liver weight abnormal histological findings in the liver and abnormal biochemical parameters related to liver function were observed in male and/or female rats in 5 mg/kg group and higher dose groups The noobservedeffect level for 44′butylidenebis2tertbutyl5methylphenol was concluded to be 5 mg/kg/day In the uterotrophic assay of 3dibutylaminophenol female SD rats were subcutaneously injected with the chemical at doses of 0 100 300 and 1000 mg/kg on each of 3 days from postnatal day 20 to day 22 and no changes were observed In the Hershberger assay of 3dibutylaminophenol the test chemical was orally administered at doses of 0 50 200 and 400 mg/kg/day to castrated male SD rats for ten consecutive days beginning on postnatal day 56 and no changes were observed On the other hand when this test chemical was orally administered at doses 0 30 100 and 300 mg/kg/day for at least 28 days in the subacute oral toxicity study thyroid weight increased in the male rats in the 300 mg/kg group thyroid follicular epithelial cell hypertrophy was observed in a small number of male rats in the 300 mg/kg group serum T3values decreased in the female rats in the 300 mg/kg group and a tendency for TSHvalues to increase was observed in the male and female rats in the 300 mg/kg group Therefore 3dibutylaminophenol was also concluded to have slight antithyroid acting effects as the endocrinemediated effects On the other hand increased hemosiderin deposition in the spleen increased spleen weight hematological abnormalities and squamous epithelial hyperplasia of the forestomach were detected in male and/or female rats in the 100 and/or 300 mg/kg groups and thus the noobservedeffect level for 3dibutylaminophenol was concluded to be 30 mg/kg/day

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