Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) in rats. 1. Acute and subchronic toxicity.

The acute and subchronic toxicity studies on 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) were conducted using male and female Wistar rats. In acute toxicity test, the LD50 values were estimated to be greater than 10 g/kg BW by oral and intraperitoneal administration in each sex. In subchronic toxicity test, groups of 10 rats of each sex were fed a diet containing 0.2, 1.0 or 5.0% of MBEBP and examined at 4 and 12 weeks. Body weight gain was significantly depressed at doses of 1.0 and 5.0% in both sexes, but the depression in the 1.0% group was severer than that in the 5.0% group in males. Hematological analysis showed slight but significant decrease of hemoglobin in the 1.0 and 5.0% groups of both sexes. Urine analysis showed no remarkable changes in all treated rats of both sexes. In biochemical analysis of serum, decrease of triglyceride level and cholinesterase activity, and increase of amylase activity were observed in treated rats. Histopathologically, testicular atrophy and decrease of spermatogenesis were observed in male rats fed 1.0 or 5.0% MBEBP for 4 and 12 weeks and vacuolization of parathyroid gland cells was observed in female rats fed 1.0 and 5.0% MBEBP for 12 weeks. In subchronic test, the lowest observable adverse effect levels for MBEBP toxicity were estimated to be 171 mg/kg BW/day in male rats and 180 mg/kg BW/day in female rats.