title: Oral bioaccessibility testing and read-across hazard assessment of nickel compounds.
abstract: 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 (mgNi released/mg available Ni × 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.
authors.affiliation: NiPERA, Inc., 2525 Meridian Parkway, Suite 240, Durham, NC 27713, USA. rhenderson@nipera.org
authors.forename: Rayetta G
authors.initials: RG
authors.lastname: Henderson
authors.forename: Danielle
authors.initials: D
authors.lastname: Cappellini
authors.forename: Steven K
authors.initials: SK
authors.lastname: Seilkop
authors.forename: Hudson K
authors.initials: HK
authors.lastname: Bates
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Oller
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007419:Intestinal Secretions / Q000737:chemistry; D009532:Nickel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D018570:Risk Assessment / Q000379:methods*; D018675:Toxicity Tests
chemical_list: C029938:nickel sulfate; C022838:nickel chloride; D009532:Nickel; C028007:nickel monoxide