Vanadium pentoxide: Use of relevant historical control data shows no evidence for a carcinogenic response in F344/N rats

The National Toxicology Program (NTP) chronic inhalation bioassay of vanadium pentoxide (V2O5) produced “clear” evidence of lung tumors in B6C3F1 mice, but only “some” and “equivocal” evidence in male and female F344/N rats, respectively. No significant pairwise differences or trends with V2O5 concentration in male or female rat poly-3-adjusted tumor incidence were reported. The “some” and “equivocal” evidence descriptors arose from comparisons of V2O5-exposed group incidence rates with NTP-2000- and NIH-07-fed historical control (HC) group incidence ranges. NTP acknowledged that use of data from NIH-07-fed HC groups could be inappropriate because the V2O5 study used the NTP-2000 diet, but few studies using this newer diet were available then. We supplemented the early NTP-2000 diet HC data with data from 25 additional NTP-2000 diet studies conducted subsequent to the V2O5 bioassay. This widened the HC tumor incidence ranges, thereby weakening the limited evidence for the carcinogenicity of inhaled V2O5 in rats relative to HCs. The male rat control group in the V2O5 study also appeared to be a near-“outlier” relative to the expanded HC database, potentially invalidating any comparisons of exposed group incidence rates with those for HCs. We conclude that there is “no” evidence of V2O5 carcinogenicity in male or female F344/N rats.