Pathologic changes in rats and dogs from two-year feeding of sodium arsenite or sodium arsenate

Abstract

Feeding of sodium arsenite or sodium arsenate to weanling Osborne-Mendel rats in 2-year experiments resulted in marked enlargement of the common bile duct in a large proportion of the animals on the highest dosage of each compound, namely, 250 and 400 ppm As in the diet, respectively. These levels also caused pronounced weight depression and decreased survival. At the next lower dosages, 125 ppm As as arsenite and 250 ppm As as arsenate in the diet, enlargement of the common bile duct was also present, but was less pronounced. Survival was slightly reduced with the arsenate, and both compounds caused reduced weight, particularly in the females. Levels of 62.5, 31.25, or 15.63 ppm As as arsenite and 125, 62.5, or 31.25 ppm As as arsenate did not cause common bile duct enlargement and did not affect survival. Weight was slightly reduced in both sexes with 125 ppm As as arsenate, and in females only with 62.5 ppm As as arsenite. No carcinogenic effect of the two arsenicals in these experiments could be detected. Histologically, the enlarged common bile ducts showed hyperplasia of the glandular elements, focal necrosis, and fibrosis. Intrahepatic bile ducts were little affected. Young beagle dogs in a 2-year experiment were fed either of the arsenicals at As levels of 125, 50, 25, or 5 ppm in the diet. None of the six on the high level of arsenite survived 2 years; all lost much weight during the feeding period. Only one of six dogs on the high level of arsenate died, and this one dog lost much weight; the survivors showed some weight loss. Gross and microscopic changes in the nonsurviving dogs were essentially those of inanition. Dogs on levels of 50 ppm or less of As as either compound did not differ from the controls. For a given degree of effect in either species (dog survival and weight loss, rat survival and weight depression, and rat common bile duct enlargement), more arsenic in arsenate than in arsenite form was required.