Comparative subchronic oral toxicity of sulphite and acetaldehyde hydroxysulphonate in rats

A subchronic oral toxicity study of sodium metabisulphite and acetaldehyde hydroxysulphonate was conducted in normal and sulphite oxidase-deficient rats. At the highest dose level (350 mg SO2 equiv./kg body weight/day for 3 wk followed by 175 mg SO2 equiv./kg body weight/day for 5 wk of either compound), gastric lesions were noted histologically in both normal and sulphite oxidase-deficient rats. The lesions were more severe and more frequently encountered in the sulphite oxidase-deficient rats. The no-effect level for Na2S2O5 was 70 mg SO2 equiv./kg body weight/day in both normal and sulphite oxidase-deficient rats. Liver lesions were noted in rats treated with acetaldehyde hydroxysulphonate. These lesions may possibly be attributable to the effects of free acetaldehyde. The no-effect level for acetaldehyde hydroxysulphonate was 7 mg SO2 equiv./kg body weight/day for sulphite oxidase-deficient rats and 70 mg SO2 equiv./kg body weight/day for normal rats. Increased urinary excretion of sulphite was noted in sulphite oxidase-deficient rats whether or not they were given exogenous sulphites. An increase in urinary sulphite levels in sulphite oxidase-deficient rats was observed after dosing with acetaldehyde hydroxy-sulphonate. These findings suggest that acetaldehyde hydroxysulphonate is metabolized to acetaldehyde and free sulphite.