Lower-Than-Expected Vitamin A Concentrations in a Commercial Diet Associated with Uroliths and Pyelonephritis in Rats

Abstract

Five of 95 rats in an oral safety study developed uroliths, with two of these rats also developing pyelonephritis. Histology of the urinary tract revealed squamous metaplasia suggestive of vitamin A deficiency. Analysis of the diet showed around half the expected concentration of vitamin A, although the concentrations were close to the published nutritional requirements for rats. Due to the presence of squamous metaplasia of the transitional epithelium and the low vitamin A concentration in the diet, a presumptive diagnosis of vitamin A deficiency was made, although an interaction between the low vitamin A concentrations and other dietary components appears possible. Although the uroliths did not cause clinical signs of disease, the lesions observed during this study could have been misinterpreted as being due to the test substance. Observations from this study highlight the need for high-quality food to ensure background lesions do not develop when performing safety studies in rats.