Nickel sulphide

Endpoint summary

Additional information

Four studies characterizing the in vivo toxicokinetic properties of NiS in rats were identified. These studies evaluated toxicokinetics associated with various routes of administration (e.g., oral, inhalation, and intramuscular [i.m.]), and for various durations of exposure (<1 day to 1 month). Most of these studies evaluated the clearance and distribution of other nickel-containing compounds in addition to NiS. The toxicokinetic studies generally evaluated distribution and clearance of NiS to and from various organs (e.g., primarily lung, liver, kidney, spleen, pancreas), blood and urine. The studies only evaluated a single dose and compared tissue concentrations to control animals.

Tanaka et al. (1988; 1992) conducted a series of studies evaluating distribution and retention of NiS in rats following a 1-month inhalation exposure to NiS. Findings indicated that nickel levels in several tissues were elevated immediately after exposure, but decreased to control levels 6 months following exposures. The authors also concluded that the lung clearance rate was inversely related to solubility. Similar findings were reported by Ishimatsu et al. (1995): only 2.1% of a single oral NiS dose was measurable in organs, blood or urine 24 hr after exposure. The authors suggested that the kinetic behavior of Ni compounds administered orally is closely related with the solubility of Ni compounds. Results reported by Novelli et al. (1995) support these findings; in this study, intramuscular NiS administration resulted in systemic distribution and absorption of nickel in some tissues 72 hours following injection. Collectively, these data indicate that Ni from NiS administered via various routes (e.g., oral, inhalation, and i.m.) can distribute to various organs, such as the lung, liver and kidney. However, it is cleared or eliminated fairly quickly. Though none of the available studies alone are sufficient to fully characterize the distribution of NiS, the data when considered collectively provide a general understanding of the toxicokinetics following oral, inhalation or i.m. administration of NiS in rats. However, data were not located regarding toxicokinetics in other species.

For the purpose of risk characterisation, the absorption of nickel from inhalation of nickel sulphide in rats is read across from the estimate for nickel subsulphide. For nickel subsulphide, the inhalation absorption in rats is conservatively estimated to be 50%, compared to 100% for nickel sulphate hexahydrate. The retention half time for nickel subsulphide was twice as long as for nickel sulphate hexahydrate (4 days versus 2 days) in the study by Bensonet al., (1994). The factor of 2 is also conservative based on the relative Ni ion release in synthetic lung fluids (KMHC, 2010). The relative Ni ion releases in synthetic lung fluids for nickel sulphide and nickel subsulphide are very comparable, further justifying the read across from nickel subsulphide to nickel sulphide (KMHC, 2010). Regarding the oral absorption of Ni from nickel sulphide in rats, based on the Ishimatsuet al(1995), the absorption is considered to be 5-fold lower than from nickel sulphate hexahydrate. For nickel sulphate values of 30% and 5% are used for oral nickel absorption under fasting conditions or with food, respectively, which were derived from Nielsen et al (1999). The resulting oral absorption values for nickel sulphide are 6% (30% ÷ 5) and 1% (5% ÷ 5) for fasting and non-fasting, respectively.