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Information characterizing the toxicokinetics of nickel hydroxide in experimental animals is lacking. Severalin vitrostudies have evaluated the dissolution rates of nickel dihydroxide or of various preparations of nickel (di) hydroxide. Data on the bioaccessibility of Ni dihydroxide in six biological fluids as a surrogate for bioavailability are reported within Section 7.1.1 of this IUCLID file (KMHC, 2010). In addition, Kasprzaket al.(1983) measured the rate of dissolution of (a) colloidal nickel(II) hydroxide (COL), (b) air-dried nickel(II) hydroxide (DRY), and (c) crystalline industrial nickel(II) hydroxide (CRST), in human blood serum, artificial lung fluid, and ammonium acetate buffer. Additional qualitative excretion and tissue distribution data in humans were reported in studies surveying occupationally exposed nickel battery workers (see Human Surveillance section); however exposure was not quantitatively evaluated and thus specific evaluation of kinetics is not possible.

 

For inhalation absorption, nickel dihydroxide can be conservatively read across from nickel oxide. Results of bioaccessibility studies show that the release of Ni in synthetic lung fluids (e.g., alveolar, interstitial) from Ni dihydroxide most closely resembles that of Ni oxides: Ni release after 72 hours as percent of available Ni was < 1% for green and black NiO and < 0.1% for Ni dihydroxide (KMHC, 2010). For oral absorption, nickel dihydroxide is also read across from nickel oxide since both compounds had similar Ni releases in synthetic gastric fluid (26.3% and 29.6%, respectively) (KMHC, 2010; Henderson et al., 2012a). The oral absorption of nickel oxide is very low (0.04% for nickel oxide compared to 11.12% for nickel sulphate in rats; Ishimatsu et al., 1995). Therefore, a 278-fold difference in oral absorption between nickel oxide and nickel sulphate was carried over to the risk characterization based on human data from Nielsen et al. (1999) where approximately 30% of nickel ion was absorbed under fasting conditions. Dividing this value by the 278-fold lower absorption of nickel oxide results in 0.1% oral absorption under fasting conditions. 

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

A comprehensive read-across program based on bioaccessibility data in synthetic fluids andin vivoacute oral toxicity data has been conducted on a series of Ni substances including Ni dihydroxide. The results of this program suggest that Ni dihydroxide should be read-across from Ni oxide for oral systemic exposure. Reviews have demonstrated thatis no data on inhalation absorption of nickel oxide (green or black) but it is expected to be low. To estimate the difference between the inhalation absorption of nickel from nickel oxide and from nickel sulphate, the relative retention half times in rats are considered (T1/2 = 2 days for nickel sulphate and 120 days for nickel oxide, Benson et al., 1994). The value of 60 is conservative compared to the relative Ni ion release in synthetic alveolar and interstitial lung fluids after 72 hours:  0.1% alveolar-0.1% interstitial for nickel oxide-green, 0.7% alveolar -0.8% interstitial for nickel oxide-black, 48% alveolar -57% interstitial for nickel sulphate, KMHC, 2010].

For the purpose of risk characterisation, a value of 1.7% is taken forward for the risk characterisation as the absorbed fraction of nickel from the respiratory tract following inhalation exposure to nickel oxide (respirable size) in rats and through extrapolation, nickel dihydroxide. The oral absorption of nickel oxide is very low (0.04% for nickel oxide compared to 11.12% for nickel sulphate in rats; Ishimatsu et al., 1995). Therefore, a 278-fold difference in oral absorption between nickel oxide and nickel sulphate was carried over to the risk characterization of nickel oxide and, through read-across, nickel dihydroxide (0.1% oral absorption under fasting conditions).