Gradient, Cambridge, Massachusetts 02138, USA.
Crit Rev Toxicol. 2011 Feb;41(2):142-74. doi: 10.3109/10408444.2010.531460. Epub 2010 Dec 16.
The inhalation of nickel-containing dust has been associated with an increased risk of respiratory cancer in workplaces that process and refine sulfidic nickel mattes, where workers are exposed to mixtures of sulfidic, oxidic, water-soluble, and metallic forms of nickel. Because there is great complexity in the physical and chemical properties of nickel species, it is of interest which specific nickel forms are associated with carcinogenic risk. A bioavailability model for tumor induction by nickel has been proposed, based on the results of animal inhalation bioassays conducted on four nickel-containing substances. The nickel ion bioavailability model holds that a nickel-containing substance must release nickel ions that become bioavailable at the nucleus of epithelial respiratory cells for the substance to be carcinogenic, and that the carcinogenic potency of the substance is proportional to the degree to which the nickel ions are bioavailable at that site. This hypothesis updates the nickel ion theory, which holds that exposure to any nickel-containing substance leads to an increased cancer risk. The bioavailability of nickel ions from nickel-containing substances depends on their respiratory toxicity, clearance, intracellular uptake, and both extracellular and intracellular dissolution. Although some data gaps were identified, a weight-of-evidence evaluation indicates that the nickel ion bioavailability model may explain the existing animal and in vitro data better than the nickel ion theory. Epidemiological data are not sufficiently robust for determining which model is most appropriate, but are consistent with the nickel ion bioavailability model. Information on nickel bioavailability should be incorporated into future risk assessments.
吸入含镍粉尘与在处理和精炼硫化镍冰铜的工作场所中患呼吸道癌症的风险增加有关，在这些场所中，工人接触的是硫化物、氧化物、水溶性和金属镍的混合物。由于镍的物理和化学性质非常复杂，因此，哪些特定的镍形态与致癌风险有关，这一点很让人关注。基于对四种含镍物质进行的动物吸入生物测定的结果，提出了镍诱导肿瘤发生的生物利用度模型。镍离子生物利用度模型认为，一种含镍物质必须释放镍离子，这些镍离子在呼吸道上皮细胞的核中变得具有生物利用度，该物质才具有致癌性，并且该物质的致癌效力与镍离子在该部位的生物利用度成正比。这一假设更新了镍离子理论，该理论认为，接触任何含镍物质都会增加癌症风险。镍离子从含镍物质中的生物利用度取决于其呼吸毒性、清除率、细胞内摄取以及细胞外和细胞内溶解。尽管确定了一些数据空白，但综合证据评估表明，镍离子生物利用度模型可能比镍离子理论更好地解释现有的动物和体外数据。流行病学数据不足以确定哪种模型最合适，但与镍离子生物利用度模型一致。镍生物利用度信息应纳入未来的风险评估中。
