Progress report on multigeneration reproduction studies in rats fed butylated hydroxytoluene (BHT)

Abstract

Weanling rats have been fed 20% fat diets containing 0, 300, 1000 or 3000 ppm butylated hydroxytoluene (BHT; 3,5-di- tert-butyl-4-hydroxytoluene). At 100 days of age, 16 females on each dietary level were mated with males on the same dietary level. Fertility, parturition and lactation were examined in the parents, and viability, survival, growth, and behaviour examined in the offspring. Ten days after weaning of the first litter, the females were mated a second time and the same examinations made on parents and offspring. Numerous function and clinical tests were performed on the parents after 28 wk on experimental diets and complete gross and microscopic pathology performed after weaning of the second litter, after 42 wk on test diets. After weaning of the second litter, these offspring were fed the same diets as their parents until 100 days of age and mated in the same procedure. The same observations were made on these animals and 2 litters of offspring. A third generation is still under study. At the 3000 ppm dietary level of BHT, a 10–20% reduction in growth rate of parents and offspring was observed. A 20% elevation of serum cholesterol levels was observed after 28 wk, but no cholesterol elevation after 10 wk. A 10–20% increase in relative liver weight was also observed in animals killed after 42 wk on diet. All other observations at 3000 ppm and all observations at 1000 and 300 ppm were comparable with those of the control group. All criteria of reproduction were normal. No teratogenic effects were detected. By all criteria, in 2 generations of parent rats and their offspring, a “no-effect” level of 1000 ppm of BHT in a high fat diet is established.