Chronic oral toxicity of a synthetic antioxidant, 2,2'-methylenebis(4-ethyl- 6-tert-butylphenol), in rats.

Groups of 30 Wistar rats of each sex were treated with 2,2'-methylenebis(4-ethyl-6-tert-butylphenol) (MBEBP) in the diet at levels of 0, 0.03, 0.1 and 0.3% for up to 18 months. In both sexes, survival rates of treated groups were similar to those of the controls. Body weight gain was depressed (0.3% group in males, 0.1 and 0.3% groups in females). Slight anaemia (0.3% groups in both sexes) and increase of blood urea nitrogen (0.3% groups in both sexes) were observed. Histopathologically, vacuolization of the parathyroid gland cells (0.3% group in males and all treated groups in females) and degenerative changes of the kidney (0.1 and 0.3% groups in males) were observed. No neoplastic responses following MBEBP administration were noted. From these results, the no-observed-adverse-effect level (NOAEL) for MBEBP toxicity was estimated as 12 mg kg-1 body wt. day-1 in male rats. In female rats, the lowest-observed-adverse-effect level (LOAEL) was estimated as 15 mg kg-1 body wt. day-1.