Oral bioaccessibility testing and read-across hazard assessment of nickel compounds
Oral bioaccessibility testing and read-across hazard assessment of nickel compounds
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DOI：
10.1016/j.yrtph.2012.02.005
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发表时间：
2012-06-01
影响因子：
3.4
通讯作者：
Oiler, Adriana R.
中科院分区：
文献类型：
--
作者：
Henderson, Rayetta G.;Cappellini, Danielle;Oiler, Adriana R.
体外金属离子生物可及性，作为生物利用度的一种度量，可用于从数据丰富的源物质到数据贫乏的靶物质的毒性信息的交叉读取。为了满足欧洲REACH法规对口服全身毒性终点的数据要求，对12种镍物质进行了胃液和肠液中的生物可及性试验。基于胃生物可及性与体内急性经口毒性之间的相关性，开发了一种交叉阅读范式。口服LD 50值可以通过镍释放量很好地预测（R-2 = 0.91）。释放2000毫克/千克的样品;而释放>76%有效镍的样品的半数致死剂量预计在300至2000毫克/千克之间。基于三种来源镍化合物（硫酸盐、低硫化物、氧化物）的交叉读数，评价了所有口服全身终点的危害分类（欧洲化学物质和混合物分类、标签和包装法规）。从硫酸镍读取释放76% Ni的样品。该评估表明，氯化镍和氢氧化镍的分类不应太严格，氨基磺酸镍的口服全身终点分类应比目前指定的更严格。(C)2012 Elsevier Inc. All rights reserved.
In vitro metal ion bioaccessibility, as a measure of bioavailability, can be used to read-across toxicity information from data-rich, source substances to data-poor, target substances. To meet the data requirements for oral systemic toxicity endpoints under the REACH Regulation in Europe, 12 nickel substances underwent bioaccessibility testing in stomach and intestinal fluids. A read-across paradigm was developed based on the correlation between gastric bioaccessibility and in vivo acute oral toxicity. The oral LD50 values were well predicted by nickel release (R-2 = 0.91). Samples releasing 2000 mg/kg; while samples releasing >76% available nickel are expected to have an LD50 between 300 and 2000 mg/kg. The hazard classifications (European Regulation on Classification, Labelling and Packaging of Chemical Substances and Mixtures) for all oral systemic endpoints were evaluated based on read-across from three source nickel compounds (sulfate, subsulfide, oxide). Samples releasing 76% Ni were read-across from nickel sulfate. This assessment suggests that nickel chloride and dihydroxide should be less stringently classified and nickel sulfamate should receive a more stringent classification for oral systemic endpoints than currently assigned. (C) 2012 Elsevier Inc. All rights reserved.