Journal
REGULATORY TOXICOLOGY AND PHARMACOLOGY
Volume 63, Issue 1, Pages 20-28Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yrtph.2012.02.005
Keywords
Nickel; Metal; Acute toxicity; Oral; REACH; Read-across; Rat; Classification; Bioavailability; Bioaccessibility
Categories
Funding
- Nickel REACH Consortia
- Nickel Producers Environmental Research Association, Inc.
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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 <48% available nickel (mg Ni released/mg available Ni x 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. (C) 2012 Elsevier Inc. All rights reserved.
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