Chromium Toxicokinetics

  • E. J. O’Flaherty
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 115)


Chromium (Cr) toxicokinetics is the toxicokinetics of two different oxidation states, Cr(III) and Cr(VI), linked by reduction processes that are ubiquitous in body fluids and tissues. The kinetic behaviors of these two major oxidation states of chromium are very different. Reduction of Cr(VI) to Cr(III) in the body, the lung, and the gastrointestinal tract is sufficiently rapid that bulk chromium kinetics may be considered to be the kinetics of Cr(III). However, certain detectable differences in chromium disposition depend upon whether exposure is to a Cr(III) or a Cr(VI) salt. In addition, the reduction process itself is of interest relative to the carcinogenicity of Cr(VI) in the lung. Therefore, a comprehensive understanding of the toxicokinetics of chromium must include the disposition of both Cr(III) and Cr(VI).


Total Chromium Chromium Compound Chromium Picolinate Lead Chromate Sodium Chromate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander J, Mikalsen A, Ryberg D (1986) Microsomal reduction of Cr VI. Acta Pharmacol Toxicol (Copenh) 59:267–269CrossRefGoogle Scholar
  2. Anderson RA (1986) Chromium metabolism and its role in disease processes in man. Clin Physiol Biochem 4:31–41PubMedGoogle Scholar
  3. Anderson RA, Kozlovsky AS (1985) Chromium intake, absorption and excretion of subjects consuming self-selected diets. Am J Clin Nutr 41:1177–1183PubMedGoogle Scholar
  4. Anderson RA, Polansky MM, Bryden NA, Roginski EE, Mertz W, Glinsmann W (1983) Chromium supplementation of human subjects:effects on glucose, insulin, and lipid variables. Metabolism 32:894–899PubMedCrossRefGoogle Scholar
  5. Anderson RA, Polansky MM, Bryden NA, Canary J (1987) Supplemental chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets. Am J Clin Nutr 54:909–916Google Scholar
  6. Appenroth D, Bräunlich H (1988) Age dependent differences in sodium dichromate nephrotoxicity in rats. Exp Pathol 33:179 - 185PubMedCrossRefGoogle Scholar
  7. Banks RB, Cooke RT Jr (1986) Chromate reduction by rabbit liver aldehyde oxidase. Biochem Biophys Res Commun 137:8–14PubMedCrossRefGoogle Scholar
  8. Becker N, Claude J, Frenzel-Beyme R (1985) Cancer risk of arc welders exposed to fumes containing chromium and nickel. Scand J Work Environ Health 11:75–82PubMedCrossRefGoogle Scholar
  9. Bianchi V, Levis AG (1988) Review of genetic effects and mechanisms of action of chromium compounds. Sci Total Environ 71:351–355PubMedCrossRefGoogle Scholar
  10. Bishop C, Surgenor M (eds) (1964) The red blood cell:a comprehensive treatise. Academic, New YorkGoogle Scholar
  11. Bragt PC, van Dura EA (1983) Toxicokinetics of hexavalent chromium in the rat after intratracheal administration of Chromates of different solubilities. Ann Occup Hyg 27:315–322PubMedCrossRefGoogle Scholar
  12. Cavalleri A, Minoia C, Richelmi P, Baldi C, Micoli G (1985) Determination of total and hexavalent chromium in bile after intravenous administration of potassium dichromate in rats. Environ Res 37:490–496PubMedCrossRefGoogle Scholar
  13. Chen NSC, Tsai A, Dyer IA (1973) Effect of chelating agents on chromium absorption in rats. J Nutr 103:1182–1186PubMedGoogle Scholar
  14. Cikrt M, Bencko V (1979) Biliary excretion and distribution of 51Cr(III) and 51Cr(VI) in rats. J Hyg Epidemiol Microbiol Immunol 23:241–246PubMedGoogle Scholar
  15. DeBetto P, Luciani S (1988) Toxic effect of chromium on cellular metabolism. Sci Total Environ 71:365–377PubMedCrossRefGoogle Scholar
  16. DeFlora S, Badolati GS, Serra D, Picciotto A, Magnolia MR, Savarino V (1987) Circadian reduction of chromium in the gastric environment. Mutat Res 192:169–174CrossRefGoogle Scholar
  17. DeFlora S, Bagnasco M, Serra D, Zanacchi P (1990) Genotoxicity of chromium compounds. A review. Mutat Res 238:99–172Google Scholar
  18. Donaldson RM Jr, Barreras RF (1966) Intestinal absorption of trace quantities of chromium. J Lab Clin Med 68:484–493PubMedGoogle Scholar
  19. Edel J, Sabbioni E (1985) Pathways of Cr(III) and Cr(VI) in the rat after intratracheal administration. Hum Toxicol 4:409–416PubMedCrossRefGoogle Scholar
  20. Evans GW (1989) The effect of chromium picolinate on insulin controlled parameters in humans. Int J Biosoc Med Res 11:163–180Google Scholar
  21. Fornace AJ, Seres DS, Lechner JF, Harris CC (1981) DNA-protein cross-linking by chromium salts. Chem Biol Interact 36:345–354PubMedCrossRefGoogle Scholar
  22. Franchini I, Mutti A (1988) Selected toxicological aspects of chromium ( VI) compounds. Sci Total Environ 71:379–387PubMedCrossRefGoogle Scholar
  23. Gad SC (1989) Acute and chronic systemic chromium toxicity. Sci Total Environ 86:149–157PubMedCrossRefGoogle Scholar
  24. Gibb H, Chen C (1989) Evaluation of issues relating to the carcinogen risk assessment of chromium. Sci Total Environ 86:181–186PubMedCrossRefGoogle Scholar
  25. Goyer RA (1990) Environmentally related diseases of the urinary tract. Environ Med 74:377–389Google Scholar
  26. Gray SJ, Sterling K (1950) The tagging of red cells and plasma proteins with radioactive chromium. J Clin Invest 29:1604–1613PubMedCrossRefGoogle Scholar
  27. Gumbleton M, Nicholls PJ (1988) Dose-response and time-response biochemical and histological study of potassium dichromate-induced nephrotoxicity in the rat. Food Chem Toxicol 26:37–44PubMedCrossRefGoogle Scholar
  28. Hahn CJ, Evans GW (1975) Absorption of trace metals in the zinc-deficient rat. Am J Physiol 228:1020–1023PubMedGoogle Scholar
  29. Hathaway JA (1989) Role of epidemiologic studies in evaluating the carcinogenicity of chromium compounds. Sci Total Environ 86:169–179PubMedCrossRefGoogle Scholar
  30. Hopkins LL Jr (1965) Distribution in the rat of physiological amounts of injected Cr51(III) with time. Am J Physiol 209:731–735PubMedGoogle Scholar
  31. Hopkins LL Jr, Schwarz K (1964) Chromium ( III) binding to serum proteins, specifically siderophilin. Biochim Biophys Acta 90:484–491PubMedGoogle Scholar
  32. Ivankovic S, Preussmann R (1975) Absence of toxic and carcinogenic effects after administration of high doses of chromic oxide pigment in sub-acute and long-term feeding experiments in rats. Food Cosmet Toxicol 13:347–351PubMedCrossRefGoogle Scholar
  33. Kawanishi S, Inoue S, Sano S (1986) Mechanism of DNA cleavage induced by sodium chromate ( VI) in the presence of hydrogen peroxide. J Biol Chem 261:5952–5958PubMedGoogle Scholar
  34. Kraintz L, Talmage RV (1952) Distribution of radioactivity following intravenous administration of trivalent chromium 51 in the rat and rabbit. Proc Soc Exp Biol Med 81:490–492PubMedGoogle Scholar
  35. Langård S (1990) One hundred years of chromium and cancer:a review of epidemiological evidence and selected case reports. Am J Ind Med 17:189–215PubMedCrossRefGoogle Scholar
  36. Langård S, Gundersen N, Tsalev DL, Gylseth B (1978) Whole blood chromium level and chromium excretion in the rat after zinc chromate inhalation. Acta Pharmacol Toxicol 42:142–149CrossRefGoogle Scholar
  37. MacKenzie RD, Byerrum RU, Decker CF, Hoppert CA, Langham RF (1958) Chronic toxicity studies. II. Hexavalent and trivalent chromium administered in drinking water to rats. AMA Arch Ind Health 18:232–234PubMedGoogle Scholar
  38. MacKenzie RD, Anwar RA, Byerrum RU, Hoppert CA (1959) Absorption and distribution of Cr51 in the albino rat. Arch Biochem Biophys 79:200–205CrossRefGoogle Scholar
  39. Mertz W (1969) Chromium occurrence and function in biological systems. Physiol Rev 49:163–239PubMedGoogle Scholar
  40. Mertz W, Roginski EE (1971) Chromium metabolism:the glucose tolerance factor. In:Mertz W, Cornatzer WE (eds) Newer trace elements in nutrition. Dekker, New York, pp 123–153Google Scholar
  41. Mertz W, Roginski EE, Reba RC (1964) Biological activity and fate of trace quantities of intravenous chromium ( III) in the rat. Am J Physiol 209:489–494Google Scholar
  42. Mossop RT (1983) Effects of chromium (III) on fasting glucose, cholesterol and cholesterol HDL levels in diabetics. Cent Afr J Med 29:80–82PubMedGoogle Scholar
  43. National Research Council (1989) RDA (Recommended Dietary Allowance), 10th edn. National Academy Press, WashingtonGoogle Scholar
  44. Norseth T, Alexander J, Aaseth J, Langard S (1982) Biliary excretion of chromium in the rat:a role of glutathione. Acta Pharmacol Toxicol (copenh) 51:450–455CrossRefGoogle Scholar
  45. Petrilli FL, De Flora S (1988) Metabolic reduction of chromium as a threshold mechanism limiting its in vivo activity. Sci Total Environ 71:357–364PubMedCrossRefGoogle Scholar
  46. Raithel HJ, Schaller KH, Reith A, Svenes KB, Valentin H (1988) Investigations on the quantitative determination of nickel and chromium in human lung tissue. Int Arch Occup Environ Health 60:55–66PubMedCrossRefGoogle Scholar
  47. Riales R, Albrink MJ (1981) Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high density lipoprotein of adult men. Am J Clin Nutr 34:2670–2678PubMedGoogle Scholar
  48. Rossi SC, Wetterhahn KE (1989) Chromium ( V) is produced upon reduction of chromate by mitochondrial electron transport chain complexes. Carcinogenesis 10:913–921PubMedCrossRefGoogle Scholar
  49. Stern RM (1983) Assessment of risk of lung cancer for welders. Arch Environ Health 38:148–155PubMedGoogle Scholar
  50. Tsapakos MJ, Wetterhahn KE (1983) The interaction of chromium with nucleic acids. Chem Biol Interact 46:265–277PubMedCrossRefGoogle Scholar
  51. Verschoor MA, Bragt PC, Herber RFM, Zielhuis RL, Zwennis WCM (1988) Renal function of chrome-plating workers and welders. Int Arch Occup Environ Health 60:67–70PubMedCrossRefGoogle Scholar
  52. Visek WJ, Whitney IB, Kuhn USG III, Comar CL (1953) Metabolism of Cr51 by animals as influenced by chemical state. Proc Soc Exp Biol Med 84:610–615PubMedGoogle Scholar
  53. Wang MM, Fox EA, Stoecker BJ, Menendez CE, Chan SB (1989) Serum cholesterol of adults supplemented with brewer’s yeast or chromium chloride. Nutr Res 9:989–998CrossRefGoogle Scholar
  54. Weber H (1983) Long-term study of the distribution of soluble chromate-51 in the rat after a single intratracheal administration. J Toxicol Environ Health 11:749–764PubMedCrossRefGoogle Scholar
  55. Wetterhahn KE, Hamilton JW (1989) Molecular basis of hexavalent chromium carcinogenicity:effect on gene expression. Sci Total Environ 86:113–129PubMedCrossRefGoogle Scholar
  56. Witmer CM, Harris R (1991) Chromium content of bone after oral and intraperitoneal (ip) administration of chromium (VI) to rats (Abstr). Toxicologist 11:41Google Scholar
  57. World Health Organization (1988) Environmental health criteria 61:chromium. IPCS International Programme on Chemical Safety. World Health Organization, GenevaGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • E. J. O’Flaherty

There are no affiliations available

Personalised recommendations