Developmental neurobehavioural toxicity of butylated hydroxytoluene in rats

Abstract

Butylated hydroxytoluene (BHT) was fed to rats throughout development (from before conception through to day 90 of postnatal life) at levels of 0, 0·125, 0·25 or 0·5% (w/w) in the diet. A similarly treated positive control group was injected on day 12 of gestation with 550 mg/kg of the antimitotic/embryotoxic drug hydroxyurea for reference. Offspring from all groups were reared by their natural dams and were evaluated in a battery of behavioural tests from day 3 to day 90 after birth. BHT at 0·5% in the diet reduced the body weights of dams and of offspring during early development and increased offspring mortality (to 39%) up to 30 days of age. This dose delayed eyelid opening, surface-righting development and limb co-ordination in swimming in males, and reduced female open-field ambulation; however, no significant effects were found after weaning. The lower doses of BHT produced some irregularities in maternal weight (0·25% an increase and 0·125% a decrease) but had no effect on the body weights of offspring. BHT at 0·25% of the diet increased pre- and periweaning mortality (23%), but neither this dose nor the 0·125% dose had any effect on physical or behavioural development or on post-weaning behavioural performance. The positive control group treated with hydroxyurea showed reduced growth prior to weaning, reduced adult brain weight and a slight but nonsignificant increase in pre- and periweaning mortality (10%). This group also exhibited delayed eyelid opening, delayed forward locomotor development and limb co-ordination during swimming, but showed no effects on postweaning behavioural performance. The BHT findings are consistent with the existing toxicological literature that BHT is toxic to growing rodents at doses of 0·25 or 0·5% of the diet with marginal effects at 0·125% of the diet. The behavioural data expand the picture of BHT's toxicity, but do not suggest any disproportionate or special toxicity of BHT for the central nervous system.