Matte, nickel

Endpoint summary

Description of key information

The acute oral LD50 of three Ni matte samples has been shown to be greater than 5,000 mg/kg bw (EPSL, 2009a-c).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Nickel matte has a harmonized EU CLP classification. Ni matte does not carry a classification for acute toxicity in the 1st ATP to the CLP Regulation. To confirm this classification and determine if any additional classifications may be warranted, toxicological testing results were identified and assessed. In addition, the UVCB classification was calculated by applying the CLP mixture rules based on the classification of the known or worst-case speciation of each constituent and worst-case constituent concentration in the UVCB (i.e. the maximum value of the typical concentration reported by the individual legal entities), using the MeClas tool. Three in vivo studies investigating the acute toxicity of Ni matte were identified. All three in vivo studies were acute oral toxicity tests (Up and Down Procedure) conducted with rats to determine the potential for nickel matte to produce toxicity from a single dose via the oral route (EPSL 2009a-c). Under the conditions of these studies, the acute oral LD₅₀of each test substance was determined to be greater than the highest dose tested (5,000 mg/kg bw) in female rats. The nickel matte samples tested for acute oral toxicity represented each of the three groups of nickel matte compositions. Read-across within these groups is justified as each composition within each group has the same mineralogy and very similar compositions, with the compositions within each group differing only for classification purposes by the level of cobalt. Since cobalt levels are low (e.g. <=6%) in all compositions, and cobalt does not contribute to the classification of this endpoint, read-across within each group is justified for this endpoint. The MeClas tool was used to automatically calculate the classification of the intermediate to confirm the harmonized classification as well. The tool is based on a database containing the human and environmental classification for each component relevant for classification. The information on the representative mineralogical composition (distribution pattern for each constituent of the UVCB substance) is furthermore incorporated into the tool, for applying the mixture rules. The MeClas tool confirmed the in vivo results using the mixtures rules calculation. 

For inhalation and dermal toxicity classification,the MeClas tool was used to calculate the classification of the intermediate. No classification was warranted for dermal toxicity. MeClas indicated that nickel matte would be classified by CLP mixtures rule as acutely toxic by inhalation Cat 4, driven by nickel subsulphide. However, due to the availability of robust acute toxicity data via the oral route and both gastric and alveolar bioaccessibility data for all three groups of nickel matte (See attached CSR Section 5.1), the oral toxicity data can be read across to the inhalation route on the basis of absorbed systemic dose of nickel from both routes. The absorbed systemic dose of nickel by the oral route at the LD₅₀can be calculated by considering both the gastric bioelution and oral absorption percentages of nickel The orally absorbed systemic dose of nickel can be converted to the equivalent air concentration leading to the same systemic dose in rats according to the formula found in the Guidance on the Application of the CLP Criteria (EC) No 1272/2008 for extrapolation between oral and inhalation routes (1 mg Ni/kg bw = 0.0052 mg Ni/L/4h). The result of that formula is divided by the alveolar bioelution percentage of nickel to calculate the equivalent air concentration for each nickel matte group, which can be compared to the cutoff for classification of 5 mg/l/4hr. Those calculations were performed as follows:

Nickel Matte (sulphidic high-copper) group

 

>5000 mg/kg (oral LD₅₀) X 28.2 % (gastric nickel bioelution percentage) X 30% (gastric nickel absorption) = >423 mg/kg systemically absorbed by oral route

 

>423 mg/kg X 0.0052 mg/L/4h (CLP extrapolation factor between inhlated and oral routes) = >2.2 mg/L/4hr

>2.2 mg/L/4h / 0.04% (alveolar nickel bioelution percentage) = > 55mg/L/4h

 

Thus, the oral LD50 for Nickel Matte (sulphidic high-copper) of >5000 mg/kg is equivalent to an inhalation exposure of > 55 mg/L/4h. This indicates that Nickel Matte (sulphidic high-copper) should not be classified for acute toxicity by inhalation, since the classification criteria apply to concentrations less than or equal to 5 mg/l/4hr. 

 

Nickel Matte (sulphidic low-copper) group

 

>5000 mg/kg (oral LD₅₀) X 42.5 % (gastric nickel bioelution percentage) X 30% (gastric nickel absorption) = >638 mg/kg systemically absorbed by oral route

 

>638 mg/kg X 0.0052 mg/L/4h (CLP extrapolation factor between inhlated and oral routes) = >3.3 mg/L/4hr

>3.3 mg/L/4h / 0.01% (alveolar nickel bioelution percentage) = > 332 mg/L/4h

 

Thus, the oral LD50 for Nickel Matte (sulphidic high-copper) of.>5000 mg/kg is equivalent to an inhalation exposure of > 332 mg/L/4h. This indicates that Nickel Matte (sulphidic low-copper) should not be classified for acute toxicity by inhalation, since the classification criteria apply to concentrations less than or equal to 5 mg/l/4hr. 

 

Nickel Matte (metallic)

 

>5000 mg/kg (oral LD₅₀) X 77.4 % (gastric nickel bioelution percentage) X 30% (gastric nickel absorption) = > 1161 mg/kg systemically absorbed by oral route

 

>1161 mg/kg X 0.0052 mg/L/4h (CLP extrapolation factor between inhlated and oral routes) = >6.0 mg/L/4hr

>6.0 mg/L/4h / 0.02% (alveolar nickel bioelution percentage) = > 301 mg/L/4h

 

Thus, the oral LD50 for Nickel Matte (sulphidic high-copper) of.>5000 mg/kg is equivalent to an inhalation exposure of > 301 mg/L/4h. This indicates that Nickel Matte (metallic) should not be classified for acute toxicity by inhalation, since the classification criteria apply to concentrations less than or equal to 5 mg/l/4hr. 

As Ni matte is considered a UVCB with variable composition, the availability of reliable data on multiple samples, read-across based on bioelution data, and MeClas calculations can be combined to provide important information regarding the potential toxicity of nickel mattes. Taken together, nickel matte is not classified for acute toxicity.

 

The following information is taken into account for any hazard / risk assessment:

For oral toxicity, the acute oral LD₅₀of three Ni matte samples has been shown to be greater than 5,000 mg/kg bw (EPSL, 2009a-c), which is the cutoff for acute toxicity. This no classification was warranted by mixtures rules calculations by MeClas. For dermal toxicity, no classification was warranted by mixtures rules calculations by MeClas. Read-across to the inhalation route, using gastric and alveolar bioelution data with systemic absorption rates for oral and inhalation exposure, indicates that nickel matte should not be classified as acutely toxic by inhalation Cat 4 as indicated by MeClas mixtures rules calculations. The resulting lack of acute toxicity classification is consistant with the lack of classification for this endpoint in the harmonized EU CLP classification of nickel matte.

Value used for CSA:

Nickel matte is not classified for acute toxicity by any route.

Justification for classification or non-classification

Ni matte does not carry a classification for acute toxicity in the 1st ATP to the CLP Regulation. This is supported by the three acute oral toxicity studies across nickel matte groups described above in which the oral LD₅₀was concluded to be >5000 mg/kg bw. Mixtures rules classification indicates a lack of classification is warranted for dermal toxicity. Read-across from oral toxicity studies using bioelution data supports the lack of acute toxicity classification by inhalation. 

·   See furthermore attached documents:

Please refer to IUCLID section 13 or CSR Appendix I for detailed MeClas printouts with the specified input concentrations and resulting classification. Please visit www.meclas.eu for more information about the tool.