Food and cosmetics toxicology最新文献

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.

Toxicity resulting from exposure to sulphite originating both endogenously and exogenously was investigated in normal rats and in rats made sulphite-oxidase-deficient by molybdenum deficiency abetted by administration of tungstate. The sulphite-oxidase-deficient rats were outwardly as healthy as controls and exhibited normal weight gain and maintenance over the 9-wk test period. The systemic sulphite exposures of normal and deficient rats resulting from various sulphite treatments could be compared by determining the concentrations of tissue S-sulphonate (RS-SO₃⁻) metabolites formed. In general, relatively low intakes of exogenous sulphite (0–3·5 mmol/kg/day) by sulphite-oxidase-deficient rats produced systemic sulphite exposures equivalent to those produced by the ingestion by normal rats of highly sulphited diets (intakes of 13–25 mmol/kg/day). The advantages of the sulphite-oxidase-deficient rat compared to the normal rat as a model for human exposure are discussed. Using these two animal models, it was demonstrated that anaemia and thiamine deficiency, which have been produced previously in sulphite-feeding studies, result solely from the action of high concentrations of sulphite in the diet and/or gut and are not attributable to systemic sulphite exposure. Likewise, prothrombin time and erythrocyte concentrations of glutathione were not affected by high systemic sulphite concentrations in these experiments.

A $\text{4}\text{149}$ incidence of mammary adenocarcinoma was observed in sulphite-oxidase-deficient rats, all in rats aged less than 5 months, compared to $\text{0}\text{143}$ observed in age-matched rats with normal sulphite oxidase. Although this result was not statistically significant, the rarity of spontaneous tumours of this type among rats of this age suggests that these carcinomas may, in fact, have been treatment related. If indicated, further investigation will be undertaken to determine the role of sulphite-oxidase-deficiency, sulphite and/or tungstate, as well as other elements of the model, in the aetiology of these tumours.