Long-term toxicity and carcinogenicity studies of cake made from chlorinated flour. 1. Studies in rats.
Wistar rats were fed for 104 wk on cake-based diets in which the cake, prepared from unchlorinated flour, or flour treated with 1250 or 2500 ppm chlorine, formed 79% of the diet on a 12.6% moisture basis. A fourth group was fed stock diet 41B. No differences in appearance, health, behaviour or mortalities attributable to the flour treatment were observed. Female but not male mortalities were significantly higher for cake-fed rats than for those fed diet 41B. Dose-related haematological effects were seen at various stages in cake-fed rats. Dose-related increases in plasma alanine and aspartate aminotransferases were noted at 12 months in males but not in females, for whom all the values were elevated. A dose-related diminution in blood sugar at 12 months was seen only in females. A dose-related increase in urinary aspartate aminotransferase was seen only in males. Urinary N-acetylglucosaminidase activity per mg creatinine did not differ significantly between groups. At post mortem a dose-related reduction in spleen weight was found in the females only. The lesions found were those expected in ageing rats, but were observed earlier in rats fed cake. Glomerulonephrosis affected rats fed cake more than those fed diet 41B. Cake diets promoted nephrocalcinosis, unrelated to flour treatment. Increased splenic haematopoiesis occurred in about half of the females in the cake diet groups but less frequently in males or in rats fed diet 41B. Tumours were mainly chromophobe adenomas of the pituitary, common in rats. Insulomas were seen in two males in each of the groups fed on cake made from chlorinated flour, but an earlier form of this tumour was found in all cake groups and its incidence is thus regarded as unrelated to the flour treatment. The incidence of tumours of the reticuloendothelial system was not related to flour treatment. Covalent chlorine concentrations in the perirenal fat of the cake-fed rats were correlated with treatment levels, with values of 50-912 ppm in males and 59-1174 ppm in females. Since concentrations in the lipid of the diet fed to the animals were much higher than these, accumulation of the additive was absent or negligible. The chlorine concentrations in the perirenal fat of male and female rats fed diet 41B were 62 and 72 ppm respectively.