Abstract
Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent
chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study,
Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI)
studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP
study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards
for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality)
was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal
lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and
rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings
demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal
pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response.