Toxicology Consulting Services, Bonita Springs, FL, USA.
David White Chemical and Metallurgical Consulting, Apex, NC, USA.
Regul Toxicol Pharmacol. 2020 Jun;113:104650. doi: 10.1016/j.yrtph.2020.104650. Epub 2020 Apr 1.
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 (VO), 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 VO. In sum, the NTP VO 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.
评估钒化合物对健康的影响引起了监管部门的关注，但目前可用的慢性毒性数据有限。美国国家毒理学计划（NTP）对结晶五氧化二钒（VO）进行了一项强有力的慢性吸入生物测定，但这项研究存在显著的局限性。在两个不同的实验室进行了多次剂量范围发现研究，结果表明两种物种的肺部病理学（炎症）存在实验室间差异，可能使剂量选择复杂化。在小鼠中，唯一的组织病理学（炎症和肿瘤）发生在呼吸系统的进入部位。尽管与对照组有显著差异，因为在所有测试浓度下，肺部肿瘤发生率都达到了最高水平，但将风险外推到公众的能力存在问题。在大鼠中，肺部炎症和钒肺负荷与小鼠相当，但未证实肺癌的发生，这进一步引发了关于适当物种外推的问题。关于测试材料化学特性的问题也存在疑问，因为实验室依赖于测试室中的钒测量作为 VO 的替代物。总之，NTP 的 VO 研究不能为分类和风险评估提供适当的数据集。需要对钒化合物进行额外的重复暴露研究，并为未来的研究提供建议。
