[13-week subchronic toxicity study of 1,1-bis(t-butylperoxy) 3,3,5-trimethyl cyclohexane in mice].
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)
M
M
Mitsui
F
F
Furukawa
J
J
Suzuki
T
T
Enami
A
A
Nishikawa
M
M
Takahashi
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003510:Cyclohexanes / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D003510:Cyclohexanes; C067220:di-tert-butylperoxy-3,3,5-trimethylcyclohexane peroxide