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Carcinogenic risks of inorganic arsenic in perspective

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Abstract

Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.

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References

  1. Chen C-J, Wang CJ (1990) Ecological correction between arsenic level in well water and age-adjusted mortality from malignant neoplasms. Cancer Res 550:5470–5474

    Google Scholar 

  2. Lamm SH, Lederer WH (1985) Inorganic arsenic: The importance of accurate exposure characterization in risk assessment. In: Risk analysis in the private sector. Whipple C, Covello VT (eds) Plenum Press, New York, pp 149–163

    Google Scholar 

  3. Intemational Agency For Research on Cancer, IARC monographs on the evaluation of the carcinogenic risk of chemicals to man, Vol. 23, Some metals and metallic compounds. World Health Organization, Lyon, France (1980)

    Google Scholar 

  4. Petito CT, Beck BD (1991) Evaluation of evidence of nonlinearities in the dose-response curve for arsenic carcinogenesis. Trace Subst Environ Health 24:143–176

    Google Scholar 

  5. Bates MN, et al. (1992) Arsenic ingestion and internal cancers: a review. Am J Epidemiol 135:462–476

    Google Scholar 

  6. Smith TJ, et al. (1977) Airborne arsenic exposure and excretion of methylated arsenic compounds. Environ Health Persp 19:89–93

    Google Scholar 

  7. Chakraborty AK, Saha KC (1987) Arsenical dermatoses from tubewell water in west Bengal. Ind J Med Res 85:326–334

    Google Scholar 

  8. Tsuda T, et al. (1995) Ingested arsenic and internal cancer: a historical cohort followed for 33 years. Am J Epidemiol 141:198–209

    Google Scholar 

  9. Cebrian ME, et al. (1983) Chronic arsenic poisoning in the north of Mexico. Human Toxicol 2:121–133

    Google Scholar 

  10. Lou Z-D, et al. (1995) Chronic Arsenicism and Cancer in Inner Mongolia -Consequences of Arsenic in Deep Wells. J Environ Geochem Health (in press)

  11. Zalvidar R (1974) Arsenic contamination of drinking water and foodstuffs causing endemic chronic poisoning. Bitrage Pathologica 151:384–400

    Google Scholar 

  12. Tseng WP, et al. (1968) Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Nat Cancer Inst 40:453–463

    Google Scholar 

  13. Chen C-J, et al. (1988) Atherogenicity and carcinogenicity of high arsenic artesian well water: multiple risk factors and related malignant neoplasms of blackfoot disease. Arteriosclerosis 8:452–460

    Google Scholar 

  14. Chang T-C, et al. (1991) Higher prevalence of goiter in endemic area of blackfoot disease of Taiwan. J Formosan Med Assoc 90:941–946

    Google Scholar 

  15. Lu J-N, Chen C-J (1991) Prevalence of hepatitis B surface antigen carrier status among residents in the endemic area of chronic arsenicism in Taiwan. Anticancer Res 11:229–234

    Google Scholar 

  16. Wu M-M, et al. (1989) Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. Am J Epidemiol 130:1123–1132

    Google Scholar 

  17. Fierz VU (1965) Katamnestische Untersuchungen über die Nebenwirkungen der Therapie mit anorganischem Arsen bei Hautkrankheiten. Dermatologica 131:41–58

    Google Scholar 

  18. Goldsmith JR (1972) Evaluation of health implications of elevated arsenic in well water. Water Res 6:1133–1136

    Google Scholar 

  19. Harrington JM, et al. (1978) A survey of a population exposed to high concentrations of arsenic in well water in Fairbanks, Alaska. Am J Epidemiol 108:377–385

    Google Scholar 

  20. Southwick JW, et al. (1983) An epidemiological study of arsenic in drinking water in Millard County, Utah. In: Lederer WH, Fensterheim RJ (eds) Arsenic: industrial, biomedical, environmental perspectives. Van Nostrand Reinhold, New York, pp 210–225

    Google Scholar 

  21. Tay C-H, Seah C-S (1975) Arsenic poisoning from anti-asthmatic herbal preparations. Med J Austria 2:424–428

    Google Scholar 

  22. Armitage P, Doll R (1961) Stochastic models for carcinogenesis. In: Neyman J (ed) Proceedings of the Fourth Berkeley Symposium on mathematical statistics and probability 4:19–38

  23. Crump KS, et al. (1976) Fundamental carcinogenic processes and their implications for low dose risk assessment. Cancer Res 36:2973–2979

    Google Scholar 

  24. Crump KS, et al. (1977) Confidence intervals and tests of hypothesis concerning dose response relations inferred from animal carcinogenicity data. Biometrics 33:437–451

    Google Scholar 

  25. Lu FJ (1990) Blackfoot disease: arsenic or humic acid? Lancet 336:115–116

    Google Scholar 

  26. Lin SM, Yang MH (1988) Arsenic, selenium, and zinc in patients with blackfoot disease. Biol Trace Elem Res 15:213–221

    Google Scholar 

  27. Pontius FW, et al. (1994) Health implications of arsenic in drinking water. J Am Water Works Assoc, September: pp 52–63

  28. Vahter M (1983) Metabolism of arsenic, In: Fowler BA (ed) Biological and Environmental Effects of Arsenic. Elsevier Science Press, New York

    Google Scholar 

  29. Vahter M, Marafante E (1985) Reduction and binding of arsenate in Marmoset monkeys. Arch Toxicol 57:119–124

    Google Scholar 

  30. Deak ST, Csaky KC, Waddell WJ (1976) Localization and histochemical correlation of 73As by whole-body autoradiography in mice. J Toxicol Environ Health 1:981–984

    Google Scholar 

  31. Lindgren A, Vahter M, Dencker L (1982) Autoradiographic studies on the distribution of arsenic in mice and hamsters administered 74As-Arsenate or Arsenate. Acta Pharmacol Toxicolog 51:253–265

    Google Scholar 

  32. Jung C, Rothstein A, (1965) Arsenate uptake and release in relation to the inhibition of transport and glycolysis in yeast. Biochem Pharmacol 14:1093–1112

    Google Scholar 

  33. McKinney JD, (1992) Metabolism and disposition of inorganic arsenic in laboratory animals and humans. Environ Geochem Health 14:43–48

    Google Scholar 

  34. Thomas DJ (1994) Arsenic toxicity in humans: research problems and prospects. Environ Geochem Health 16:107–111

    Google Scholar 

  35. Thompson DJ (1993) A chemical hypothesis for arsenic methylation in mammals. Chem Biol Interactions 88:89–114

    Google Scholar 

  36. Endo G, et al. (1992) Dimethylarsenic acid induces tetraploids in Chinese hamster cells. Bull Environ Contamin Toxicol 48:131–137

    Google Scholar 

  37. Shirachi DY, et al. (1983) Tumorigenic effect of sodium arsenite in rat kidney. Proceeding of the Western Pharmacology Society 26:413–415

    Google Scholar 

  38. Yamamoto S, et al. (1995) Cancer induction by an organic arsenic compound, dimethylarsenic acid (cacodylic acid), in F344/ DuCrj rats after pretreatment with five carcinogens. Cancer Res 55:1271–1276

    Google Scholar 

  39. Yamanaka K, et al. (1991) Cellular response to oxidative damage in lung induced by the administration of dimethylarsenic acid, a major metabolite of inorganic arsencs, in mice. Toxicol Appl Pharmacol 108:205–213

    Google Scholar 

  40. Vahter M, Envall J (1983) In vivo reduction of arsenate in mice and rabbits. Environ Res 32:14–24

    Google Scholar 

  41. Marcus WL, Rispin AS (1988) Threshold carcinogenicity using arsenic as an example. In: Cothern CR, Mehlman MA, Marcus WL (eds) Risk Assessment and Risk Management of Industrial and Environmental Chemicals. Princeton Scientific, N.J., pp 133–158

    Google Scholar 

  42. Valentine JL, Kang HK, Spivey G (1979) Arsenic levels in human blood, urine, and hair in response to exposure via drinking water. Environ Res 20:24–31

    Google Scholar 

  43. Brown CC, Chu KC (1983) Implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure. J Nat Cancer Ins 70:455–463

    Google Scholar 

  44. Jacobson-Kram D, Montalbano D (1985) The reproductive effects assessment group's report on the mutagenicity of inorganic arsenic. Environ Mutagen 7:787–804

    Google Scholar 

  45. Lee T-C, et al. (1985) Comparison of arsenic-induced cell transformation, cytotoxicity, mutation, and cytogenic effects in Syrian hamster embryo cells in culture. Carcinogenesis 6:1421–1426

    Google Scholar 

  46. Bauman JW, Liu J, Klaassen CD (1993) Production of metallothionine and heat shock proteins by metals. Fundam Appl Toxicol 21:15–22

    Google Scholar 

  47. Moolgavkar SH (1991) Carcinogenesis models: an overview. Bas Life Sci 58:387–96

    Google Scholar 

  48. Vig BK, et al. (1984) Chromosome studies in human subjects chronically exposed to arsenic in drinking water. Am J Ind Med 6:325–338

    Google Scholar 

  49. Brown KG, Chen C-J (1994) On the observed dose-response for internal cancers and arsenic in drinking water in the Blackfoot disease endemic region of Taiwan. In: Arsenic: exposure and health. Chappell WR, Abernathy CO, Cothem CR, (eds) First International Conference on Arsenic Exposure and Health Effects. Sci Technol Lett, Northwood, England, pp 153–169

    Google Scholar 

  50. Brown KG, Chen C-J (1995) Significance of exposure assessment to analysis of cancer risk from inorganic arsenic in drinking water in Taiwan. Risk Analysis Vol. 15:475–484

    Google Scholar 

  51. Smith AH, et al. (1992) Cancer risks from arsenic in drinking water. Environ Health Persp 97:259–267

    Google Scholar 

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Authors and Affiliations

  1. Risk Assessment and Product Safety, Consultants in Toxicology, Suite 1150, 1225 New York Ave. NW, 20005, Washington, DC, USA

    Daniel M. Byrd & M. Luann Roegner

  2. International Specialty Products, 1361 Alps Road, 07470, Wayne, NJ, USA

    James C. Griffiths

  3. Consultants in Epidemiology and Occupational Health, Inc., 2428 Wisconsin Ave., NW, 20007, Washington, DC, USA

    Steven H. Lamm & Karen S. Grumski

  4. Lyman Laboratory of Physics (231), Harvard University, 11 Oxford Street, 02138, Cambridge, MA, USA

    Richard Wilson

  5. Biostatistical Working Group, University of Miami, Room 2001 (D-91), 1800 NW 10th Avenue, 33136, Miami, FL, USA

    Shenghan Lai

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  1. Daniel M. Byrd
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  2. M. Luann Roegner
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  3. James C. Griffiths
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  4. Steven H. Lamm
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  5. Karen S. Grumski
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  6. Richard Wilson
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  7. Shenghan Lai
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Byrd, D.M., Roegner, M.L., Griffiths, J.C. et al. Carcinogenic risks of inorganic arsenic in perspective. Int Arch Occup Environ Health 68, 484–494 (1996). https://doi.org/10.1007/BF00377874

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