Copper alloys' metal migration and bioaccessibility in saliva and gastric fluid.

The oral bioaccessibility of copper alloys and pure metals was assessed using in vitro methods with synthetic saliva and gastric fluid. The metal-specific migration rates from polished alloy surfaces are higher in gastric (pH 1.5) than in saliva fluid (pH 7.2). In both media, migrations are higher for lead than for other metals. The bioaccessible metal concentrations in massive copper alloys, after 2 h in gastric fluid, was only <0.01%-0.18%, consistent with the low surface reactivity of copper alloys (defined as 1 mm spheres). The average metal-specific migrations of cobalt, copper, nickel and lead from most of the tested copper alloys in gastric media are comparable to the ones from their pure metals. The data further show that the bioaccessibility of metals in massive copper alloys primarily depends on the bioelution medium, the exposed surface area and the composition of the alloy. The tested copper alloys show only limited evidence for influence of alloy surface microstructure. This is contrary to findings for other alloys such as stainless steel. Additional investigations on other copper alloys could allow to further refine these conclusions. These findings are useful for establishing the hazard and risk profile of copper alloys following oral exposure.

Bioaccessibility of nickel and cobalt in synthetic gastric and lung fluids and its potential use in alloy classification.

This study investigated nickel and cobalt ion release from the metals and several alloys in synthetic gastric, as well as interstitial and lysosomal lung fluids. Results were used to calculate the relative bioaccessible concentrations (RBCs) of the metals. Nickel release from SS 316L powder in gastric fluid was >300-fold lower than from a simple mixture of powders of the same bulk composition. Gastric bioaccessibility data showed 50-fold higher metal releases per gram of sample from powder than massive forms. RBCs of nickel and cobalt in the alloy powders were lower, equal, or higher in all fluids tested than their bulk concentrations. This illustrates the fact that matrix effects can increase or decrease the metal ion release, depending on the metal ingredients, alloy type, and fluid, consistent with research by others. Acute inhalation toxicity studies with cobalt-containing alloy powders showed that the RBC of cobalt in interstitial lung fluid predicted acute toxicity better than bulk concentration. This example indicates that the RBC of a metal in an alloy may estimate the concentration of bioavailable metals better than the bulk concentration, and the approach may provide a means to refine the classification of alloys for several human health endpoints.

Inter-laboratory validation of bioaccessibility testing for metals.

Bioelution assays are fast, simple alternatives to in vivo testing. In this study, the intra- and inter-laboratory variability in bioaccessibility data generated by bioelution tests were evaluated in synthetic fluids relevant to oral, inhalation, and dermal exposure. Using one defined protocol, five laboratories measured metal release from cobalt oxide, cobalt powder, copper concentrate, Inconel alloy, leaded brass alloy, and nickel sulfate hexahydrate. Standard deviations of repeatability (sr) and reproducibility (sR) were used to evaluate the intra- and inter-laboratory variability, respectively. Examination of the sR:sr ratios demonstrated that, while gastric and lysosomal fluids had reasonably good reproducibility, other fluids did not show as good concordance between laboratories. Relative standard deviation (RSD) analysis showed more favorable reproducibility outcomes for some data sets; overall results varied more between- than within-laboratories. RSD analysis of sr showed good within-laboratory variability for all conditions except some metals in interstitial fluid. In general, these findings indicate that absolute bioaccessibility results in some biological fluids may vary between different laboratories. However, for most applications, measures of relative bioaccessibility are needed, diminishing the requirement for high inter-laboratory reproducibility in absolute metal releases. The inter-laboratory exercise suggests that the degrees of freedom within the protocol need to be addressed.

Advances in metals classification under the United Nations globally harmonized system of classification and labeling.

This article shows how regulatory obligations mandated for metal substances can be met with a laboratory-based transformation/dissolution (T/D) method for deriving relevant hazard classification outcomes, which can then be linked to attendant environmental protection management decisions. We report the results of a ring-test at 3 laboratories conducted to determine the interlaboratory precision of the United Nations T/D Protocol (T/DP) in generating data for classifying 4 metal-bearing substances for acute and chronic toxicity under the United Nations Globally Harmonized System of Classification and Labelling (GHS) criteria with respect to the aquatic environment. The test substances were Ni metal powder, cuprous oxide (Cu(2) O) powder, tricobalt tetroxide (Co(3) O(4) ) powder, and cuttings of a NILO K Ni-Co-Fe alloy. Following GHS Annex 10 guidelines, we tested 3 loadings (1, 10, and 100 mg/L) of each substance at pH 6 and 8 for 7 or 28 d to yield T/D data for acute and chronic classification, respectively. We compared the T/DP results (dissolved metal in aqueous media) against acute and chronic ecotoxicity reference values (ERVs) for each substance to assess GHS classification outcomes. For dissolved metal ions, the respective acute and chronic ERVs established at the time of the T/D testing were: 29 and 8 µg/L for Cu; 185 and 1.5 µg/L for Co; and 13.3 and 1.0 mg/L for Fe. The acute ERVs for Ni were pH-dependent: 120 and 68 µg/L at pH 6 and 8, respectively, whereas the chronic ERV for Ni was 2.4 µg/L. The acute classification outcomes were consistent among 3 laboratories: cuprous oxide, Acute 1; Ni metal powder, Acute 3; Co(3) O(4) and the NILO K alloy, no classification. We obtained similar consistent results in chronic classifications: Cu(2) O, Ni metal powder, and Co(3) O(4) , Chronic 4; and the NILO K alloy, no classification. However, we observed equivocal results only in 2 of a possible 48 cases where the coefficient of variation of final T/D concentrations masked clear comparisons with ERVs. Results support the validity and interlaboratory precision of the United Nations T/DP in establishing GHS classification outcomes for metals and metal compounds and support its use in regulatory hazard-based systems. Drawing on T/D data derived from laboratory testing of the metal-bearing substance itself, the T/D approach can be applied to establish scientifically defensible decisions on hazard classification proposals. The resulting decisions can then be incorporated into environmental management measures in such jurisdictions as the European Union.