Oral bioaccessibility testing and read-across hazard assessment of nickel compounds

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• 作者：Rayetta G. Henderson^a ; ^{rhenderson@nipera.org} ; Danielle Cappellini^b ; ^{dcappellini@epix.net} ; Steven K. Seilkop^c ; ^{seilkop@earthlink.net} ; Hudson K. Bates^a ; ^{hbates@nipera.org} ; Adriana R. Oller^a ; ^{aoller@nipera.org}
• 关键词：Nickel ; Metal ; Acute toxicity ; Oral ; REACH ; Read-across ; Rat ; Classification ; Bioavailability ; Bioaccessibility
• 刊名：Regulatory Toxicology and Pharmacology
• 出版年：2012
• 期刊代码：57_02732300
• 类别：pha
• 出版时间：June, 2012
• 卷：63
• 期：1
• 页码：20-28
• 文件大小：450 K

摘要

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 (R² = 0.91). Samples releasing <48%available nickel (mg Ni released/mg available Ni 脳 100) are predicted to have an LD₅₀ > 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 <48%available nickel were read-across from nickel oxides and subsulfide. 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.