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Respiratory carcinogenicity assessment of soluble nickel compounds.

By Adriana R Oller


The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided

Topics: Research Article
Year: 2002
OAI identifier:
Provided by: PubMed Central

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  1. (1989). A study of mortality in workers engaged in the mining, smelting, and refining of nickel. II: Mortality from cancer of the respiratory tract and kidney.
  2. (1989). Behavior of urinary nickel in low-level occupational exposure.
  3. Beraterkreis Toxikologie.
  4. (1998). Cap43, a novel gene specifically induced by Ni2+ compounds.
  5. (1980). Carcinogenic activity of particulate nickel compounds is proportional to their cellular uptake.
  6. (1997). Carcinogenicity assessment of selected nickel compounds.
  7. (1964). Carcinogenicity of nickel compounds on experimental animals.
  8. (1983). Carcinogenicity of nickel(II) hydroxides and nickel(II) sulfate in Wistar rats and its relation to the in vitro dissolution rates.
  9. (1995). Comparative carcinogenic effects of nickel subsulfide, nickel oxide, or nickel sulfate hexahydrate on chronic exposures in the lung.
  10. (1982). Cytoplasmic dissolution of phagocytized crystalline nickel sulfide particles: a prerequisite for nuclear uptake of nickel.
  11. (1999). Deposition and clearance models of Ni compounds in the mouse lung and comparisons with the rat models.
  12. (1987). Effect of magnesium on nickel-induced genotoxicity and cell transformation.
  13. (1996). Effects of transition metals on the expression of erythropoietin gene: further evidence that the oxygen sensor is a heme protein.
  14. (2000). Epigenetic mechanisms of nickel carcinogenesis.
  15. (2001). Evaluation of the human Ni retention model with workplace data.
  16. (1996). Exposure to nickel compounds and smoking in relation to incidence of lung and nasal cancer among nickel refinery workers.
  17. (1981). Factors influencing the phagocytosis, neoplastic transformation, and cytotoxicity of particulate nickel compounds in tissue culture systems.
  18. (2000). Hazard identification and dose response of ingested nickelsoluble salts.
  19. (2000). Hazard identification and dose response of inhaled nickel-soluble salts. Regul Toxicol Pharmacol
  20. (1997). Induction of activating transcription factor I by nickel and its role as a negative regulator of thrombospondin I gene expression.
  21. (1990). Initiation by nickel acetate and promotion by sodium barbital of renal cortical epithelial tumors in male F344 rats.
  22. (1994). Lack of carcinogenic activity of promptly soluble (hydrated) and sparingly soluble (anhydrous) commercial preparations of nickel(II) sulfate in the skeletal muscle of male F334/NCR rats.
  23. (1975). Life-term effects of mercury, methyl mercury, and nine other trace metals on mice.
  24. (1974). Life-term effects of nickel in rats: survival, tumors, interactions with trace elements and tissue levels.
  25. (1998). Limit Values and Biological Exposure Indices for Chemical Substances and Physical Agents.
  26. (1976). Long term toxicologic assessment of nickel in rats and dogs.
  27. (1989). Mechanisms of nickel carcinogenesis.
  28. (1962). Metal Carcinogenesis. II: A study of the carcinogenic activity of cobalt, copper, iron and nickel compounds.
  29. (1991). Molecular mechanisms of nickel carcinogenesis.
  30. (1989). Morphological and neoplastic transformation of C3H/10T1/2
  31. (1996). Mortality study of nickel platers with special reference to cancers of the stomach and lung, 1945–93. Occup Environ Med
  32. (1981). Negative test for transplacental carcinogenicity of nickel subsulfide in Fischer rats.
  33. (2001). Nickel requires hypoxiainducible factor 1α , not redox signaling, to induce plasminogen activator inhibitor-1.
  34. (1999). Nickel-induced transformation shifts the balance between HIF-1α and p53 transcription factors.
  35. (1995). Particle clearance and histopathology in lungs of F344/N rats and B6C3F1 mice inhaling nickel oxide or nickel sulfate. Fundam Appl Toxicol
  36. (1986). Pathway of nickel uptake influences its interaction with heterochromatic DNA.
  37. (1987). Physiochemical characteristics and biological effects of nickel oxides.
  38. (1989). Promoting effect of metal compounds on liver, stomach, kidney, pancreas, and skin carcinogenesis.
  39. (1982). The regulation of ionic nickel uptake and cytotoxicity by specific amino acids and serum components.
  40. (2002). Toxicology Program. Ninth Report on Carcinogens. Available: htdocs/Liason/DecBRCBSCmin.html#nickel [accessed 19
  41. (1992). Transplacental carcinogenic effects of nickel(II) acetate in the renal cortex, renal pelvis and adenohypophysis in F344/NCr rats.
  42. (1978). Transplantation of tumors of the nervous system induced by resorptive carcinogens.
  43. (2002). Unpublished data.
  44. (1998). Update of cancer incidence among workers at a copper/nickel smelter and nickel refinery.
  45. (1994). uptake and mutagenicity of particulate and soluble nickel compounds. Environ Health Perspect 102(suppl 3):69–79
  46. (2000). VEGF expression in an osteoblast-like cell line is regulated by a hypoxia response mechanism.

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