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A 13-week subchronic toxicity study of 1,1-bis(t-butylperoxy)3,3,5-trimethyl cyclohexane (TMCH) was performed in male and female B6C3F1 mice by feeding a CRF-1 powder diet containing 0, 0.5, 1.0, 2.0 and 4.0% TMCH, to determine the maximum tolerable dose (MTD) for subsequent carcinogenicity study. Mice were randomly divided into 5 groups, each consisting of 10 males and 10 females. Eight animals of both sexes in the 4.0% TMCH group died during the early administration period. Suppression of body weight gains was marked in both sexes of the 4.0% and 2.0% TMCH groups as compared with the control group. The mean food consumption in all groups treated with TMCH was lower than that in the control group in a dose-related manner. Hematological examination revealed decreases in the number of erythrocytes, volume of hemoglobin, and values for hematocrit and mean corpuscular volume (MCV) in both sexes of the 4.0% and 2.0% TMCH groups. The relative liver weights of all groups treated with TMCH increased in a dose-related manner, whereas both absolute and relative spleen weights decreased in a dose-dependent manner. Histopathologically, swelling of the hepatocytes was found centrilobularly or diffusely in both sexes of the 1.0, 2.0 and 4.0% TMCH groups, and decrease of the hematopoietic cells in the bone marrow was observed in both sexes of the 2.0 and 4.0% TMCH groups. In addition, atrophy of red pulp and white pulp of the spleen was found in both sexes of the 2% and 4% TMCH groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,
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Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,
