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NICKEL ABSORPTION AND KINETICS IN HUMAN VOLUNTEERS
Citation:
Sweeney, K., A. Marcus, B. Most, AND J. Creason. NICKEL ABSORPTION AND KINETICS IN HUMAN VOLUNTEERS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/270.
Description:
Mathematical modelling was performed of the kinetics of nickel absorption, distribution and elimination in healthy human volunteers, who ingested NiS04 in drinking water or added food. ickel was analyzed by electrothermal atomic absorption spectrophotometry in serum, urine, and feces collected during 2 days before and 4 days after a specified NiSO4 dose (l2 ug Ni/kg, N=4; 18 ug Ni/kg, N=4; or 50 ug Ni/kg, N=1). In Exp. #1, the subjects fasted 12 hr before 3 hr after drinking the NiS04 dose dissolved in water; in Exp. #2, the subjects fasted 12 hr before consuming a standard American breakfast that contained the same dose of NiS04 added to scrambled eggs. inetic analyses, using a linear two-compartment model, provided excellent goodness-of-fit for paired data-sets from all subjects. Absorbed nickel averaged 27+ 17% (mean + SD) of the dose ingested in water versus 0.7 + 0.4% of the dose ingested in food (a 40-fold difference, p<0.001; rate constants for nickel absorption, transfer, and elimination were not significantly influenced by the oral vehicle; the elimination half-time for absorbed nickel averaged 28 + 9 hr. enal clearance of nickel averaged 8.3 + 2.0 ml/min/1.73 m2 in Exp. #1 and 5.8 + 4.3 ml/min/1.73m2 in Exp. #2. his study confirms that dietary constituents profoundly reduce the bioavailability of Ni2+ for alimentary absorption; approximately one-quarter of nickel ingested drinking water after an over-night fast is absorbed from the human intestine and excreted in urine, compared to only one percent of nickel ingested in food. he compartmental model and kinetic parameters provided by this study will reduce the uncertainty of toxicologicalrisk assessments of human exposures to nickel in drinking water and food.