Institute of Environment and Health, Cranfield University, Bedfordshire, United Kingdom.
J Toxicol Environ Health B Crit Rev. 2009 Apr;12(4):289-306. doi: 10.1080/10937400903094166.
Vanadium pentoxide (V(2)O(5)) and other inorganic vanadium compounds have recently been evaluated by several occupational exposure limit (OEL) setting (occupational exposure limit, OEL) committees and expert groups in response to the publication of several new studies, including the U.S. National Toxicology Program (NTP, 2002) carcinogenicity study of inhaled V(2)O(5) in rats and mice, which concluded that clear evidence of lung tumors was seen in mice of both genders and that there was some evidence of carcinogenicity in male rats. This study reviews the expert evaluations of several OEL committees and expert groups and attempts to understand the strengths and weaknesses in their scientific arguments. This study also evaluates some key studies relating to potential genotoxicity, carcinogenicity, and respiratory effects of vanadium compounds and discusses how they might elucidate the mechanism(s) by which V(2)O(5) induces lung cancer in mice. All expert groups appear to agree that the lung tumors induced in mice in the NTP (2002) study are a site-specific response and, in general, verify that existing in vitro and in vivo studies suggest that tumors were induced by a secondary mechanism (presumably non-genotoxic), which is supported, though not conclusively, by a mechanistic data set. As some vanadium compounds produce a range of DNA and chromosome damage, there is no consensus on which of these changes is critical for the carcinogenic process for V(2)O(5) or whether the findings for the lung tumors seen in mice exposed to V(2)O(5) can be extrapolated to other inorganic vanadium compounds. As such, the various expert committees used the evidence differently, some to read across, i.e., to predict an endpoint for a substance based on the endpoint information of another with similar characteristics (e.g., physicochemical properties [solubility, bioaccessibility, bioavailability], structure, fate [toxicokinetics], and toxicology) for carcinogenicity from V(2)O(5) to other inorganic vanadium compounds. It is noteworthy that the toxicity of metals does not necessarily relate to carcinogenicity in a direct manner; thus, no assumptions should be made a priori when trying to extrapolate from V(2)O(5) to other inorganic vanadium compounds. Recent studies evaluated in this review provided some further insights into possible mechanisms but do not cover all relevant endpoints, address only a limited number of vanadium compounds, and have not established no-effect thresholds for carcinogenicity or respiratory tract irritation. Thresholds need to be established in order for arguments to be made for setting a health-based OEL for non-genotoxic or secondary genotoxic carcinogens. In conclusion, important knowledge gaps preclude confident classification and risk assessment for all vanadium compounds. Evidence suggests that further research that may address some of these critical gaps is needed.
五氧化二钒（V(2)O(5)）和其他无机钒化合物最近已被多个职业接触限值（OEL）制定（职业接触限值，OEL）委员会和专家组评估，这是对包括美国国家毒理学计划（NTP，2002 年）在内的几项新研究的回应，该研究对吸入 V(2)O(5)的老鼠和老鼠进行了致癌性研究，研究结果表明，雌雄两性老鼠的肺部肿瘤均有明显证据，而雄性老鼠则有一些致癌性证据。本研究综述了几个 OEL 委员会和专家组的专家评估，并试图了解他们科学论点的优缺点。本研究还评估了一些与钒化合物潜在遗传毒性、致癌性和呼吸道效应有关的关键研究，并讨论了它们如何阐明 V(2)O(5)诱导老鼠肺癌的机制。所有专家组似乎都认为，NTP（2002 年）研究中诱导的老鼠肺部肿瘤是一种特定部位的反应，并且普遍证实现有的体外和体内研究表明，肿瘤是由次要机制（推测是非遗传毒性）诱导的，尽管机制数据集并不完全支持这一机制。由于一些钒化合物会产生一系列 DNA 和染色体损伤，因此对于 V(2)O(5)的致癌过程，哪种变化是关键，或者暴露于 V(2)O(5)的老鼠肺部肿瘤的发现是否可以外推到其他无机钒化合物，尚无共识。因此，各个专家委员会以不同的方式使用证据，有些委员会进行跨读，即根据另一种具有相似特征的物质的终点信息（例如，理化特性[溶解度、生物可利用性、生物利用度]、结构、命运[毒代动力学]和毒理学）预测一种物质的终点，从而将 V(2)O(5)的致癌性扩展到其他无机钒化合物。值得注意的是，金属的毒性不一定与致癌性有直接关系；因此，在试图从 V(2)O(5)外推到其他无机钒化合物时，不应预先做出任何假设。本综述评估的最新研究提供了对可能机制的进一步了解，但并未涵盖所有相关终点，仅涉及有限数量的钒化合物，并且尚未为致癌性或呼吸道刺激建立无效应阈值。为了提出基于健康的非遗传毒性或次要遗传毒性致癌剂的 OEL，需要建立阈值。总之，重要的知识差距使得所有钒化合物的分类和风险评估都没有把握。有证据表明，需要进行进一步的研究来解决其中的一些关键差距。
