Registration Dossier

Administrative data

Description of key information

ORAL: A recently completed in vivo acute oral toxicity study reported an LD50 of 2,000 mg/kg for Ni hydroxycarbonate (EPSL, 2009).
INHALATION: A recently completed in vivo acute inhalation toxicity study reported the LC50 in females to be greater than the highest dose tested (>2.09) mg/L. However, the LC50 of 0.24 mg/L concluded for males in this same study is carried forward as a conservative approach.
DERMAL: No risk characterisation will be conducted for acute dermal toxicity, following the apoproach taken in the European Union Risk Assessment for Nickel Carbonate (2008-2009). Acute systemic effects are not relevant due to the very low dermal absorption of nickel. Although nickel hydroxycarbonate carries a classification as “irritant” (Xi; R38 at concentrations above 20%; Skin Irrit. 2:H315 in the 1st ATP to the CLP Regulation), more recent data (EPSL 2008a) do not support this classification. In either case, the long term DNEL based on prevention of dermal sensitization will be sufficiently protective from any possible acute local dermal effects associated with exposure to nickel hydroxycarbonate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Due to the structural similarities of Pentanickel Octahydroxide Carbonate and Nickel Hydroxycarbonate, all information in this section is relevant for Pentanickel Octahydroxide Carbonate (see section 13 for full discussion of read-across strategy).

While there were only two studies that characterized the acute toxicity of nickel hydroxycarbonate, both studies available were conducted according to OECD guidelines using GLP standards. Thus these data sufficiently characterized lethality following oral or inhalation exposure in rats. Eurofins Product Safety Laboratories (EPSL, 2009) reported the results of an acute oral toxicity test (Up and Down Procedure) in female rats that yielded an LD50 value of 2,000 mg/kg Ni hydroxycarbonate (the 95% confidence interval for the LD50 cannot be calculated for this substance).

Eurofins Product Safety Laboratories also conducted an acute, nose-only inhalation study (EPSL, 2010) that incorporated a series of four nickel hydroxycarbonate air concentrations that ranged from 0.053 to 2.09 mg/L over a four hour exposure period. Only one of the female rats died during the study (2.09 mg/L dose group), and thus the female LC50 was considered to be >2.09 mg/L. The male rats were more sensitive to the lethal effects of nickel hydroxycarbonate, resulting in an LC50 of 0.24 mg/L (with a 95% confidence limit of 0.0012-49.7 mg/L). The findings of this study suggested that a gender-specific anion effect is likely causing increased toxicity in males as compared to females. Although the LC50 in females was greater than the highest dose tested (2.09 mg/L), the LC50 of 0.24 mg/L in males should be carried forward as a conservative approach to classification. 

No data were available characterizing endpoints other than lethality. No data were available evaluating acute toxicity following dermal or other routes of exposure. Given the available data, the oral LD50 for rats appears to be somewhere in between 1 and 2 g/kg for different hydroxycarbonate samples, while the inhalation LC50 is influenced by sex, with females being less sensitive than males by at least an order of magnitude (>2.09 vs. 0.24 mg/L).

Justification for classification or non-classification

A newly conducted GLP OECD guideline compliant study reported an LD50=2000 mg/kg for Ni hydroxycarbonate, which confirms classification for acute oral toxicity as Xn;R22 and Acute Tox. 4; H302 under the 1st ATP to the CLP Regulation (EPSL, 2009).

Ni hydroxycarbonate currently carries a minimum classification as Acute Tox 4;H332 for acute inhalation toxicity in the EU. Section 1.2.1 of the CLP Regulations states that a minimum classification "shall be applied if none of the following conditions are fulfilled:...the manufacturer or importer has access to data or other information as specified in Part 1 of Annex I that lead to classification in a more severe category compared to the minimum classification. Classification in the more severe category must then be applied". The findings of a recently completed OECD-guideline compliant study suggest that a gender-specific anion effect may be causing increased toxicity in males as compared to females. Although the LC50 in females was greater than the highest dose tested (2.09 mg/L), the LC50 of 0.24 mg/L in males should be carried forward as a conservative approach to classification. In accordance with the rules set by the CLP Regulation, the minimum classification has been changed to Acute Tox. 2:H330 within this registration file, Ni hydroxycarbonate is currently classified as Xn;R20 for acute inhalation toxicity in the EU. While the corresponding GHS classification for this endpoint has been changed (from Acute Tox. 4 to Acute Tox. 2) according to the CLP Regulation reguirements for a minimum classification the DSD classification (Xn:R20) does not carry a similiar designation as a "minimum classification". Therefore, no change to the existing harmonized classification for DSD is proposed within this registration file. A complete summary of the testing program including results and discussion are provided in Section 7.2.2 of IUCLID.