[carbonato(2-)]tetrahydroxytrinickel

Endpoint summary

Description of key information

Value used for CSA:

NOAEL (oral, systemic, animal):790 mg/kg bw (383 mg Ni/kg/day) (EPSL, 2009a)

LOAEL (oral, systemic, human):0.012 mg Ni/kg bw/day (Nielsen et al, 1999)

NOAEC (inhalation, systemic, animal): 0.053 mg/L (26 mg Ni/m³; males, MMAD=1.9 µm) (EPSL, 2010)

LOAEC (inhalation, local, animal; read-across): 0.47 mg Ni/m³ (DNEL calculation is based on 12-day repeated dose study-Benson et al, 1987; no appropriate acute data is available)

An acute local inhalation DNEL is derived based on the lung effects (e.g. lung inflammation) associated with nickel subsulphide inhalation.  The shortest-term study available examining those effects in animals is a 12-day repeated exposure study.  An adjustment factor was derived to extrapolate the results from the repeated exposure study to an equivalent effect concentration in a 4 hr acute exposure.  See Appendix C3 for more information.

(Oral, local values are not applicable; Dermal, local or systemic, values are not applicable)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

0.24 mg/L air

Additional information

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, 2009a) 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 (95% confidence interval could not be calculated) and a NOAEL of 790 mg nickel hydroxycarbonate/kg body weight.

 

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).

 

A more recent inhalation study was conducted due to some concerns regarding the EPSL 2010 study, including the possibility of a gender-specific effect, females tested at only one dose, and male data did not fit a strong dose-response curve. Product Safety Labs (PSL) conducted a nose-only inhalation study in 2021 examining the effects of both male and female rats at four nickel hydroxycarbonate air concentrations ranging from 0.05 to 5 mg/L over a four hour exposure period. Unlike the EPSL 2010 study, the female rats were more sensitive in this study with an LC₅₀ of 0.263 mg/L compared to males with 5.213 mg/L, with a combined  LC₅₀ of 0.827 mg/L. The most conservative LC₅₀ in both acute inhalation studies is 0.24 mg/L for male rats (EPSL, 2010) and 0.263 mg/L for female rats (PSL, 2021) should be carried forward as a conservative approach to classification. 

 

No data were available characterizing endpoints other than lethality.

 

There are no available data on which to evaluate acute dermal toxicity. However, acute toxicity is expected to be low in view of the poor absorption by this route. As oral and inhalation routes of exposure are more relevant and data for these have been provided. Testing for acute dermal toxicity is therefore waived based on this information.

 

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 conservatively indicated to be 0.24-0.26 mg/L).

 

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

ORAL: A recently completed GLP, guideline-based in vivo acute oral toxicity study reported an LD₅₀ of 2,000 mg/kg for Ni hydroxycarbonate and a NOAEL of 790 mg nickel hydroxycarbonate/kg body weight (EPSL, 2009).

INHALATION: Two GLP, guideline-based in vivo acute inhalation toxicity studies reported LC₅₀ values of >2.09 mg/L in females with 0.24 mg/L in males and 0.263 mg/L in females with 5.213 mg/L in males, respectively. However, the lowest LC₅₀ of 0.24 mg/L (concluded for males in the EPSL 2010 study) is carried forward as a conservative approach.

DERMAL: No risk characterisation will be conducted for acute dermal toxicity. Acute systemic effects are not relevant due to the very low dermal absorption of nickel. Acute local effects are covered by the long term DNEL based on prevention of dermal sensitization.

Justification for classification or non-classification

Nickel hydroxycarbonate is currently classified for acute oral toxicity as Acute Tox. 4; H302 according to the 1st ATP to the CLP Regulation.

 

Nickel hydroxycarbonate is currently classified for acute inhalation toxicity as Acute Tox. 4; H332 according to the 1st ATP to the CLP Regulation. However, 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". Two GLP, guideline-based in vivo acute inhalation toxicity studies reported LC₅₀ values of >2.09 mg/L in females with 0.24 mg/L in males and 0.263 mg/L in females with 5.213 mg/L in males, respectively. However, the lowest LC₅₀ of 0.24 mg/L (concluded for males in the EPSL 2010 study) is carried forward as a conservative approach. This indicates that a more stringent classification of Acute Tox. 2:H330 is warranted. In accordance with the rules set by the CLP Regulation, the current harmonized classification for acute inhalation toxicity has been changed from Acute Tox. 4;H332 to the more severe classification of Acute Tox. 2:H330 within this registration file. A complete summary of the testing program including results and discussion are provided in the CSR.

 

Ni hydroxycarbonate is not classified for acute dermal toxicity according to the 1st ATP to the CLP Regulation.