The limitations of using the NTP chronic bioassay on vanadium pentoxide in risk assessments

• Published in: Regulatory toxicology and pharmacology 2020-06, Vol.113, p.104650, Article 104650
• Main Authors: MacGregor, Judith A., White, David J., Williams, Amy Lavin
• Format: Article
• Language: English
• Subjects: Animals; Carcinogenicity; Chronic bioassay; Dose-Response Relationship, Drug; Humans; Inflammation - chemically induced; Inflammation - pathology; Inhalation; Inhalation Exposure; Lung - drug effects; Lung - pathology; Lung Neoplasms - chemically induced; Lung Neoplasms - pathology; Lung tumors; Risk; Risk Assessment; Toxicity Tests, Chronic; Vanadium Compounds - administration & dosage; Vanadium Compounds - adverse effects; Vanadium Compounds - toxicity; Vanadium pentoxide
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2020.104650

Regulatory interest in assessing the health effects of vanadium compounds is hindered by the limited chronic toxicity data available. The National Toxicology Program (NTP) conducted a robust chronic inhalation bioassay of crystalline vanadium pentoxide (V2O5), but this study has noteworthy limitations. Multiple dose range-finding studies were conducted at two separate laboratories that showed cross-laboratory differences in lung pathology (inflammation) in both species and likely complicated dose-selection. In mice, the only tissue pathology (inflammation and tumors) was at the site of entry, the respiratory system. Although significantly different from control, because lung tumor incidences were at a maximal level across all concentrations tested, the ability to extrapolate risks to the public is problematic. In rats, lung inflammation and vanadium lung burdens were comparable to those of mice, but lung tumorigenicity was not substantiated, further raising questions about appropriate species extrapolation. Open questions also exist regarding test material chemical characterization, as the laboratory relied on vanadium measurement in test chambers as a surrogate for V2O5. In sum, the NTP V2O5 study does not provide an appropriate dataset for purposes of classification and risk assessment. Additional repeat exposure studies of vanadium compounds are needed and recommendations for future studies are provided. •The NTP V2O5 chronic inhalation studies have methodological limitations to their utility for health assessments.•These studies measured chamber V concentrations, notV2O5, which is reactive and for which stability cannot be assumed.•Cross-lab and species differences in lung pathology/tumors were apparent, limiting extrapolation to humans.•Exposure concentrations were excessive; lung irritation/inflammation were apparent with short duration exposures.•Recommendations are included for future research to understand MOA and the relevance for human health.