Toxicological evaluation of malonaldehyde: a 12-month study of mice.

The chronic toxicity of malonaldehyde (MA) was evaluated using Swiss female mice. Beginning at 10 wk of age, MA was administered in the drinking water for 12 mo to groups of 50 animals at levels of 0.1, 1, and 10 micrograms/g body wt.d with 100 controls. The highest dose was associated with increased mortality (28% versus 12-14%). MA had no effect on body weight, organ weight, hematological indices, or the incidence of lesions in 27 tissues examined. More liver lesions were observed in the three treatment groups than in the controls (p less than 0.05), and the histopathologic scores for severity of lesions were significantly increased in the groups that received the two higher levels of MA. The liver lesions included anisokaryosis, changes in cytoplasmic volume with architectural derangements, necrosis and neoplastic changes (nodular hyperplasia, hepatoma, and hemangioma). There was no significant increase in specific neoplasms in the treated groups, but the incidence of total neoplasms and neoplastic lesions was dose-dependent (4%, 8%, and 12%, respectively) (p less than 0.01). There was only one neoplasm (a hemangioma) among the controls (1%). Three animals (6%) given the highest dose of MA developed stomach neoplasms. In terms of human dietary exposure to MA, the lowest level of MA used in this study is about 10 times the estimated average daily intake of MA by the Canadian population on a body weight basis.