Clinical Toxicity of Nickel
Patriarca, Marina (1995) Clinical Toxicity of Nickel. MSc(R) thesis, University of Glasgow.
In this work, I have measured the concentration of Ni in human albumin solutions used for intravenous administration, which have been produced by different manufacturers, at different times. Additional results for the concentrations of other metals, at various stages of the production process, were also obtained using multielement semiquantitative scanning by inductively coupled plasma-mass spectrometry (ICP-MS) (Chapter 2). In the last ten years, increasing efforts have been made to limit the contamination of dialysis fluids with metals, present in water, salts and haemodialysis equipment. This was intended to eliminate aluminium toxicity and may have incidentally also reduced Ni contamination. Results for Ni concentrations in the serum of haemodiaiysed patients are limited and sometimes contradictory, compared to the vast literature on serum aluminium concentrations. The assessment of Ni concentrations has proven more difficult, due to problem of pre-anaiytical contamination and the lower concentrations present. In Chapter 2 I report an investigation of the serum Ni concentrations in a group of patients undergoing regular haemodialysis and the effect a single dialysis treatment has on serum Ni concentrations in the same subjects. The understanding of the toxicology of Ni at low doses will benefit from improved knowledge of Ni biochemistry and metabolic pathways. Several studies have been carried out to investigate the metabolism of Ni in man (Nodiya, 1972; Cronin et al., 1980; Solomons et al., 1982; Gawkrodger et al., 1986; Sunderman et al., 1989) but only two report data on faecal excretion (Nodiya, 1972; Sunderman et al., 1989). There was a large inter-individual variability in the estimates of Ni absorption and excretion. In all the experiments, volunteers ingested Ni, as the naturally occurring mixture of five isotopes, and results could be affected by the contribution of Ni from diet and contamination of samples prior to analysis. Nickel metabolism has been studied in rats and rabbits using radioisotopes (63Ni, 57Ni) (Onkelinx et al., 1973; Nielsen et al., 1993) but limitations of radiation dosage prevent the application of this technique in man. The recent development of ICP-MS, which can provide information on the isotopic composition of an element using simplified procedures, offers the opportunity to apply stable isotopes for the study of mineral metabolism in humans on a larger scale. Different separation procedures were used to remove the mass interferences affecting the determination of the minor Ni isotopes in human albumin solutions, blood, erythrocytes, urine, faeces and tissues. A method was developed, that allowed the determination of three out of five Ni isotopes, one of which was used for isotopic dilution (Chapter 3). Nickel metabolism was investigated in four volunteers, who ingested a single dose of as a tracer. Nickel absorption, distribution and excretion were determined by analysing plasma, urine and faeces, collected at various time intervals for up to five days (Chapter 4). The role of Ni in the human environment and the present knowledge on its biochemistry, metabolism, health effects and analytical methods of determination are summarised in Chapter 1. (Abstract shortened by ProQuest.).
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Medicine, Toxicology