Acute, subchronic and chronic toxicity studies of a synthetic antioxidant, 2,2'-methylenebis(4-methyl-6-tert-butylphenol) in rats.
General toxicity studies on 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (MBMBP) were conducted using male and female Wistar rats. LD50 values were greater than 5 g/kg BW by oral administration for both sexes. Diarrhea was observed until 5 days. In the subchronic test, rats were fed diet containing MBMBP at 0, 0.12, 0.6 or 3.0% for 12 weeks. Severe suppression of body weight gain was observed in both sexes of 0.6 and 3.0% groups. Death accompanied by hemorrhage from nasal cavity was observed in 0.6 and 3.0% males and 3.0% females. Dose-dependent toxicity to the liver in both sexes was observed in blood chemical analysis. Histopathologically, testicular atrophy and decrease of spermatogenesis were dose- and time-dependently observed in all treated males. Atrophy of ovaries was evident in 0.6 and 3.0% females. Thymus atrophy and bone marrow hypoplasia were observed in both sexes of 0.6 and 3.0% groups. In the chronic test, rats were fed diet containing MBMBP at 0, 0.01, 0.03 and 0.1% for 18 months. Body weight gain was only suppressed in both sexes receiving 0.1%. Histopathologically, testicular atrophy and decrease of spermatogenesis were apparent in 0.1% males. No neoplastic response by MBMBP administration was noted. NOAEL was concluded to be 0.03% in the diet (12.7 mg/kg BW/day for male rats and 15.1 mg/kg BW/day for female rats).
Takagi
A
A
Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
Takada
K
K
Sai
K
K
Ochiai
T
T
Matsumoto
K
K
Sekita
K
K
Momma
J
J
Aida
Y
Y
Saitoh
M
M
Naitoh
K
K
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000633:toxicity*; D001284:Atrophy; D002084:Butylated Hydroxytoluene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004844:Epistaxis / Q000139:chemically induced; D005260:Female; D006128:Growth / Q000187:drug effects; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
D000975:Antioxidants; D002084:Butylated Hydroxytoluene; C008437:2,2'-methylenebis(4-methyl-6-tert-butylphenol)