Nickel dihydroxide

Endpoint summary

Description of key information

Skin irritation / corrosion: irritating

Eye irritation: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Information characterizing the potential for nickel dihydroxide to cause irritation/corrosion generally indicates that the compound is only slightly or mildly irritating, but not sufficient for classification. This indication is based on the results of two guideline-based, GLP studies recently conducted by Eurofins Product Safety Laboratory (EPSL) evaluating eye and skin irritation potential. The skin irritation study was conducted in rabbits according to OECD Test #404 guidelines (EPSL, 2008a). Three healthy female rabbits were exposed via the skin to nickel dihydroxide to determine if the test substance had the potential to produce irritation. Erythema was noted in all test animals at the 30-60 minute time point, but not at the remaining time intervals (up to 72 hours). No edema was observed during the study (each animal scored as 0 at all time points). The overall incidence and severity decreased with time, and the effects were fully reversible within 24 hours. The resulting Primary Dermal Irritation Index (PDII) was 0.3, indicating that nickel hydroxide was slightly irritating to the skin. According to OECD Test #404 guidelines, compounds should be considered as irritants if responses persist to the end of the observation period; however, findings of this study indicated effects were fully reversible significantly prior to the end of the observation period. However, the existing harmonized classification of Skin Irrit. 2: H315 in the 1st ATP to the CLP is carried forward in this registration file since the animal study for nickel sulphate was negative (EPSL, 2009c), while human studies demonstrated skin irritation for nickel sulphate (Frosch and Kligman, 1976; Seidenari et al, 1996). Therefore, animal data cannot be relied upon solely for lack of classification for nickel substances, though animal data has been shown to reflect current classification in the case of nickel nitrate. In the case of nickel dihydroxide, the low solubility in synthetic sweat (see Appendix B3) and negative animal data support no classification for skin irritation for nickel dihydroxide.

 

The eye irritation study was also conducted in rabbits according to OECD Test #405 guidelines (EPSL, 2008b). In this study, nickel hydroxide was instilled into the right eye of three healthy female rabbits to determine the potential to produce irritation. No corneal opacity was observed in any of the animals, though all three animals tested exhibited iritis and positive conjunctivitis one hour after instillation. All observed effects were reversible; incidence and severity of irritation decreased with time and all animals were free of ocular irritation by Day 7. The results of the study indicated that nickel hydroxide was mildly irritating to the eye under the conditions of the study. The OECD Test #405 guidelines state that extrapolation of these results to humans is only valid to a limited degree as in many cases the albino rabbit is more sensitive than humans to ocular irritants for corrosives. Therefore, no classification is warranted.

 

Collectively, these two studies provide reliable, adequate information to assess the irritant/corrosive properties of nickel (di)hydroxide. The studies were specifically designed to evaluate the health hazard likely to arise from exposure by dermal or ocular application. Results demonstrated that nickel (di)hydroxide can cause minor irritation in laboratory settings. However, all observed effects were fully reversible and generally classified as “slight” or “minor, ” thus indicating a limited potential for irritant/corrosive potential.

 

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

Although Ni dihydroxide is currently classified as a dermal irritant, the results of a recently completed GLP, OECD guideline-compliant study do not meet the criteria for classification according to the CLP regulation, and bioaccessibility testing in synthetic sweat suggests no classification is warranted. However, the existing harmonized classification of Skin Irrit. 2: H315 in the 1st ATP to the CLP is carried forward in this registration file since animal data has been shown to not be as reliable as human data for some nickel substances and bioaccessibility data has not been validated for skin irritation. A recently completed eye irritation study confirms this substance should not be classsified as an eye irritant.

Justification for classification or non-classification

Although current classification is Skin Irrit. 2: H315 in the 1st ATP to the CLP, a recently completed in vivo dermal irritation study concluded Ni dihydroxide was not an irritant, suggesting it should not be classified for this endpoint. However, the existing harmonized classification is carried forward in this registration file since animal data has been shown to not be as reliable as human data for some nickel substances and bioaccessibility data has not been validated for skin irritation.

 

An in vivo eye irritation study confirms Ni dihydroxide should not be classified for this endpoint.