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Description of key information

Key value for chemical safety assessment

Additional information

Where data are not available for nickel oxalate, data for other inorganic nickel compounds (i.e. structurally related substances) that are expected to have similar toxicity can be used for read across. For human health local effects endpoints, the bioavailability of Ni2+ at the target site determines the potential occurrence and severity of the local effects to be assessed for the read across of nickel substances. For local effects, inorganic nickel substances of similar nickel ion release and similar physical form can be used for read across. For nickel substances, the read-across strategy is predicated on the assumed presence and bioavailability of a common metal anion (e.g., Ni2 +) at the target site. This is a reasonable assumption for the majority of inorganic compounds and some organic compounds (e.g., metal salts of some organic acids) (ICCM, 2007; OECD, 2007; and ECHA, 2008), provided no significant effect of the other constituents is expected. Oxalic acid is not classified for skin or eye irritation (1st ATP to CLP)

so the oxalate ion released from nickel oxalate would not be expected to result in skin irritation.

Although it is not expected that all of the nickel ion would be released and bioavailable (based on low water solubility and relase of these ions in simulated human bodily fluids [Kirby Memorial Health Center, 2010), the worst-case approach can be taken where read across assumes the same release of nickel ions as nickel sulphate hexahydrate for nickel oxalate. This approach is not considered to be as representative of nickel toxicity potential for nickel oxalate as read across from an inorganic nickel substance of similar bioaccessibility and water solubility, but is worst-case since it represents the highest nickel ion concentration at the target sites. In the case of skin and eye irritation, the substance used for read across is nickel sulfate hexahydrate and oxalic acid. Because data for nickel sulfate hexahydrate demonstrates skin irritation, these data are used for read across. Neither nickel sulphate or oxalic acid are classified for eye irritation, so eye irritation is not expected for nickel oxalate.

References

ECHA. 2008. Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.6: QSARs and Grouping of Chemicals (Available from ECHA website: http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_r6_en.pdf?vers=20_08_08).

ICMM [International Council on Mining and Metals]. 2007. Health Risk Assessment Guidance for Metals (HERAG) (available from ICMM website: http://www.icmm.com/page/235/our-work/projects/articles/metals-risk-assessment).

Kirby Memorial Health Center. 2010. Bioaccessibility of nickel oxalate (soluble nickel analyses in simulated gastric, interstitial, and lysosomal fluids). Study Sponsor: Metallo-Chimique. Report Date: 2010-06-30.

OECD [Organisation for Economic Co-operation and Development]. 2007. Guidance on Grouping of Chemicals. Series on Testing and Assessment Number 80 (Available from the OECD website: http://www.olis.oecd.org/olis/2007doc.nsf/LinkTo/NT0000426A/$FILE/JT03232745.PDF).

Justification for classification or non-classification

Skin Irritation / Corrosion

No data are available for nickel oxalate. In an Annex V test in rabbits, nickel sulphate was not a skin irritant. However, human data indicate that nickel sulphate in concentrations above 20% can induce skin irritation. Presented in 7.10.3 "Direct Observations: clinical cases, poisoning incidents and other," Frosch and Kligman (1976) applied 0.1 mL nickel sulphate to the forearms of human subjects once daily for 3 days. Readings were made at 72 hours, 30 min after removal of the test substance. The test was conducted on both intact and scarified skin. The reactions were graded on a five-point scale from 0 to 4 (1: erythema, 2: increased erythema, 3: severe erythema with partial confluency with or without other lesions, 4: confluent severe erythema sometimes associated with oedema, necrosis or bulla formation). The threshold concentration to produce “just an irritation reaction in 3 days” on normal skin was 20.0% while on scarified skin it was 0.13%. Based on this study, nickel sulphate is classified as Xi; R38 with a specific concentration limit of 20% in the 30th ATP. Nickel sulphate has a harmonized classification of Xi:R38 and Skin Irrit. 2:H315.

Based on read-across data from nickel sulphate to the less soluble nickel oxalate, nickel oxalate is assigned the conservative classifications of Xi:R38 and Skin Irrit. Cat 2:H315 with a specific concentration limit of 20%.

Eye Irritation / Corrosion

No data are available for nickel oxalate; therefore, data for nickel sulphate hexahydrate are used as read-across. In SLI (1999), exposure to nickel sulphate hexahydrate produced iritis in 3/3 test eyes at the 1-hour scoring interval. The iritis resolved completely in all test eyes by the 48-hour scoring interval. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in all test eyes by study day 7. Based on this data, nickel sulphate hexahydrate is considered to be a mild irritant to the ocular tissue of the rabbit; however, the irritation produced completely resolved by 48 hours and was not sufficient to support DSD or GHS/CLP classification.

Taking all of the available information from read-across into account, nickel oxalate is not classified for ocular irritancy since nickel sulphate produced only mild irritation at 1 hour which had completely resolved by 48 hours. In addition, nickel oxalate was not classified for ocular irritation / corrosion in the 1st ATP to CLP.