Toxicokinetics of Nickel in Mice Studied with the γ-Emitting Isotope 57Ni

Abstract

Toxicokinetics of Nickel in Mice Studied with the γ-Emitting Isotope 57 Ni. Nielsen, G. D., Andersen, O., and Jensen, M. (1993). Fundam. Appl. Toxicol. 21, 236-243. The γ-emitting isotope 57Ni was generated in a cyclotron to allow whole-body counting of laboratory animals dosed with nickel. 57 NiCl 2 was administered either orally by gastric intubation or by intraperitoneal injection to groups of mice in doses equivalent to the average human daily dietary nickel intake per mass unit. When given orally, the whole-body retention (WBR) was 0.02-0.36% of the administered dose at 45-75 hr. When given intraperitoneally, the WBR was 1-6% at 20-50 hr. After adjustment for the rapid excretion of systemic nickel, the intestinal absorption could be estimated to be 1.7-10%. The relative WBR did not vary with the magnitude of the dose within (0.05-5 μmol Ni/kg given orally or 0.005-0.5 μmol/kg given intraperitoneally. At 8 hr, the tissue concentration was highest in the kidneys, followed by the carcass, lungs, testicles, liver, and the spleen. After 20 hr, the highest concentrations were still found in the kidneys followed by the lungs, the liver, and the carcass. At 20 hr after oral administration, 50-70% of 57Ni retained in the body was within the carcass. The second highest nickel content was found in the kidneys, followed by the liver and lungs. Whereas nickel in the kidneys was rapidly excreted, the elimination from the lungs and liver was relatively slow, thereby, after 40 hr, resulting in a higher nickel content in the liver than that in the kidneys. When nickel was given intraperitoneally, practically no nickel was transported via the portal vein to the liver after 20 hr, resulting in a low nickel content in the liver and a higher content in the kidney. These results document that the use of 57Ni for studies on nickel toxicokinetics is feasible and useful, and that the method is especially well suited for comparative studies with a duration of up to 6 days.