Nickel dihydroxide

Endpoint summary

Description of key information

Value used for CSA:

NOAEL (oral, systemic, animal data): 430 mg Ni/kg bw (Reagan 1996, FDRL 1983)

NOAEC (inhalation, systemic, animal data): 3,900 mg Ni/m³ read-across from Ni oxide (EPSL, 2009, 2010)

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

Five studies were identified characterizing the acute toxicity of nickel dihydroxide; however, primary sources of information were only available for two of these studies. All studies identified evaluated mortality as the primary endpoint; the most robust study characterizing such was conducted by EPSL (2009a). In this GLP, guideline-based study (OECD Guideline #425), the acute oral LD₅₀ was determined in female rats using the up and down procedure. Statistical evaluation of mortality data resulting from exposures ranging from 3,200 to 6,000 mg/kg indicated an oral LD₅₀ of 5,000 mg/kg body weight (95% PL confidence interval of 3,390 mg/kg to 5,800 mg/kg). In addition to mortality, animals exposed to 5,000 mg/kg nickel dihydroxide or higher exhibited clinical and behavioral adversities as well as discolored intestines upon necropsy. Reagan 1996 (also referred to as FDRL 1983) also evaluated the acute oral toxicity in young rats. Animals were exposed to single doses ranging from 1000 mg/kg to 5000 mg/kg (five dose groups) and monitored for up to 15 days. Resulting oral LD₅₀ values were 1515 mg/kg, 1565 mg/kg, and 1540 mg/kg in males, females, and both sexes combined, respectively. The remaining three reports of acute toxicity were listed in the National Institute for Occupational Safety and Health (NIOSH) Registry of Toxic Effects of Chemical Substances (RTECS) file for nickel dihydroxide. These acute effects included: (1) an LC₅₀ of 1,200 mg/m³ per four hour inhalation exposure in rats, (2) an LD₅₀ value of 50 mg/kg associated with a subcutaneous exposure in mice, and (3) an LD₅₀ value of > 2 mg/kg associated with dermal exposure in rats. However, because no study details are available for these studies, these data are not considered to be reliable (reliability score =4, not assignable). Therefore, the most relevant studies to characterize acute toxicity of nickel dihydroxide are the Reagan 1996 (also referred to as FDRL 1983) and EPSL (2009a) oral studies.

No reliable studies were available to characterize the acute inhalation toxicity of nickel dihydroxide, so data on acute inhalation toxicity of Ni dihydroxide are read-across from Ni oxide. A comprehensive read-across assessment for inhalation toxicity was recently completed based on bioaccessibility data in synthetic lung fluids of various nickel compounds combined with in vivo verification data for three source nickel substances. The read-across paradigm presented in a summary document in Section 7.2.2 and in Appendix B2 of this CSR enables grouping of target Ni substances for classification purposes according to bioaccessibility in interstitial fluid. The outcome of this assessment indicates that Ni dihydroxide should be read-across from Ni oxide (LC₅₀: > 5.08 mg Ni oxide/L air; EPSL 2009, 2010). A more recent study (PSL, 2013) supports this assessment with an LC₅₀: >8.3 mg Ni oxide/L. However, Ni dihydroxide is currently classified as Acute Tox 4: H332 in the 1^st ATP to the CLP Regulation. Therefore, although application of this read-across paradigm suggests no classification for acute inhalation toxicity is warranted, the in vitro bioaccessibility data are not sufficient to justify declassification of Ni dihydroxide for this endpoint.

There are no available data on which to evaluate acute dermal toxicity. 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.

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

ORAL: Reagan/FDRL and EPSL studies indicate a NOAEL of 430 mg Ni/kg bw (based on initial range finding study).

INHALATION: The outcome of a recently completed read-across assessment based on bioaccessibility and in vivo animal data for various nickel compounds indicates that Ni dihydroxide should be read-across from Ni oxide (LC₅₀: > 5.08 mg Ni oxide /L air), which is not classified for acute inhalation toxicity. However, Ni dihydroxide still carries a harmonized classification (Acute tox 4:H332).

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 dihydroxide is classified for acute oral toxicity as Acute Tox. 4; H302 under the 1st ATP to the CLP. A recently completed in vivo acute oral toxicity study concluded Ni dihydroxide has an LD₅₀=5,000 mg/kg suggesting it should not be classified for this endpoint. However, an older study already exists that supports a more stringent classification and aligns with the current harmonied classification under the 1st ATP to the CLP.

Nickel dihydroxide is classified for acute inhalation toxicity as Acute Tox. 4; H332 under the 1st ATP to the CLP. 

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