Past and Current Arsenic Poisonings

  • Hiroshi YamauchiEmail author
  • Ayako Takata
Part of the Current Topics in Environmental Health and Preventive Medicine book series (CTEHPM)


The health issues arising from the exposure to inorganic arsenic (iAs), an increasingly important problem in Asia, are remarkable because the source of the iAs is the natural environment and the number of people affected is in the order of tens of millions. In many cases 20–30 years have passed since the onset of exposure to high-level iAs, which raises concern about the imminent occurrence of excessive cancers related to this exposure, as this is the typical time frame for chemically induced cancer in humans. Studies conducted in Chile and Argentina, where oral exposure to iAs has a longer history than in Asia, have revealed a causal relationship between iAs and lung and bladder cancers. Furthermore, multiple studies have presented evidence that early life iAs exposures can influence the next generation by induction of tumors and brain dysfunctions. Follow-up surveys on subacute arsenic poisoning in infants that occurred about 50 years ago in Japan (approximately 12,000 victims, including 130 deaths) confirmed the manifestations of growth inhibition and central nervous system disorders. These findings over the last century provide essential information for the planning and implementation of future studies. Because it is necessary to intensify research on the influences of arsenic compounds on the next generation and on its impact on brain function, promotion of future studies involving collaboration across the fields of medicine, neurology, environmentology, pharmacy, nutritional science, and engineering is required.


Historical arsenic poisonings Chronic arsenic poisoning Inorganic arsenic contamination of drinking water Inorganic arsenic contamination of food Medicinal arsenicals 


  1. 1.
    Pinto SS, Bennett BM. Effect of arsenic trioxide exposure on mortality. Arch Environ Health. 1963;7(5):583–91.PubMedCrossRefGoogle Scholar
  2. 2.
    Lee AM, Fraumeni JF. Arsenic and respiratory cancer in man: an occupational study. J Natl Cancer Inst. 1969;42(6):1045–52.PubMedGoogle Scholar
  3. 3.
    Milham S, Strong T. Human arsenic exposure in relation to a copper smelter. Environ Res. 1974;7:176–82.CrossRefGoogle Scholar
  4. 4.
    WHO. Arsenic. Geneva: World Health Organization. Updated November 2017. Available from:
  5. 5.
    Hopenhayn-Rich C, Biggs ML, Fuchs A, Bergoglio R, Tello EE, Nicolli H, Smith AH. Bladder cancer mortality associated with arsenic in drinking water in Argentina. Epidemiology. 1996;7(2):117–24.PubMedCrossRefGoogle Scholar
  6. 6.
    Hopenhayn-Rich C, Biggs ML, Smith AH. Lung and kidney cancer mortality associated with arsenic in drinking water in Córdoba, Argentina. Int J Epidemiol. 1998;27(4):561–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Bates MN, Rey OA, Biggs ML, Hopenhayn C, Moore LE, Kalman D, Steinmaus C, Smith AH. Case-control study of bladder cancer and exposure to arsenic in Argentina. Am J Epidemiol. 2004;159(4):381–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Pou SA, Osella AR, Diaz MP. Bladder cancer mortality trends and patterns in Córdoba, Argentina (1986-2006). Cancer Causes Control. 2011;22(3):407–15. Scholar
  9. 9.
    Moore LE, Smith AH, Hopenhayn-Rich C, Biggs ML, Kalman DA, Smith MT. Micronuclei in exfoliated bladder cells among individuals chronically exposed to arsenic in drinking water. Cancer Epidemiol Biomarkers Prev. 1997;6:31–6.PubMedGoogle Scholar
  10. 10.
    Smith AH, Goycolea M, Haque R, Biggs ML. Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water. Am J Epidemiol. 1998;147(7):660–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Smith AH, Marshall G, Roh T, Ferreccio C, Liaw J, Steinmaus C. Lung, bladder, and kidney cancer mortality 40 years after arsenic exposure reduction. J Natl Cancer Inst. 2018;110:241. Scholar
  12. 12.
    IARC (International Agency for Research on Cancer). Arsenic and arsenic compounds. In:IARC Monographs on the Evaluation of the carcinogenic risks to humans, Supplement 7: Overall evaluations of carcinogenicity: an updating of IARC monographs Volumes 1 to 42. France: Lyon; 1987. p. 100–6.Google Scholar
  13. 13.
    Hutchinson J. On some examples of arsenic-keratosis of the skin and of arsenic-cancer. Trans Pathol Soc. 1888;39:352–63.Google Scholar
  14. 14.
    Neubauer O. Arsenical cancer: a review. Br J Cancer. 1947;1(2):192–251.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997;89(9):3354–60.PubMedGoogle Scholar
  16. 16.
    Reynolds ES. An account of the epidemic outbreak of arsenical poisoning occurring in beer-drinkers in the north of England and Midland Countries in 1900. Lancet. 1901;157:166–70.CrossRefGoogle Scholar
  17. 17.
    Hamamoto E. Infant arsenic poisoning by powdered milk. Nihon Iji Shinpo. 1955;1649:3–12. (in Japanese).Google Scholar
  18. 18.
    Nagai H, Okuda R, Nagami H, Yagi A, Mori C, Wada H. Subacute-chronic arsenic poisoning in infants — subsequent clinical observations. Shonika Kiyo. 1956;2:124–32. (in Japanese).Google Scholar
  19. 19.
    Yamashita N, Doi M, Nishio M, Hojo H, Tanaka M. Current State of Kyoto children poisoned by arsenic tainted Morinaga dry milk. Jap J Hyg. 1972;27:364–99. (in Japanese with English abstract).PubMedCrossRefGoogle Scholar
  20. 20.
    Ohira M, Aoyama H. Epidemiological studies on the Morinaga powdered milk poisoning incident. Jap J Hyg. 1973;27:500–31. (in Japanese with English abstract).CrossRefGoogle Scholar
  21. 21.
    Tanaka H, Oshima A. Excess mortality among 5,064 victims of arsenic poisoning from ingestion of arsenic-contaminated “Morinaga dry-milk” in 1955: a prospective study from 1982 to 2004. Nihon Koshu Eisei Zasshi. 2007;54:236–45. (in Japanese with English abstract).PubMedGoogle Scholar
  22. 22.
    Tanaka H, Tsukuma H, Oshima A. Long-term prospective study of 6104 survivors of arsenic poisoning during infancy due to contaminated milk powder in 1955. J Epidemiol. 2010;20(6):439–45. Scholar
  23. 23.
    Tseng WP. Effects and dose-response relationships of skin cancer and Blackfoot disease with arsenic. Environ Health Perspect. 1977;19:109–19.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Chen CJ, Chuang YC, Lin TM, Wu HY. Malignant neoplasms among residents of a blackfoot disease-endemic area in Taiwan: high-arsenic artesian well water and cancers. Cancer Res. 1985;45:5895–9.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Lu FJ. Blackfoot disease: arsenic or humic acid? Lancet. 1990;336:115–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Lu FJ, Hsieh HP, Yamauchi H, Yamamura Y. Fluorescent humic substances-arsenic complex in well water in areas where blackfoot disease is endemic in Taiwan. Appl Organomet Chem. 1991;5:507–12.CrossRefGoogle Scholar
  27. 27.
    Nickson R, McArthur J, Burgess W, Ahmed KM, Ravenscroft P, Rahman M. Arsenic poisoning of Bangladesh groundwater. Nature. 1998;395:338.PubMedCrossRefGoogle Scholar
  28. 28.
    Smith AH, Lingas EO, Rahman M. Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bull World Health Organ. 2000;78(9):1093–103.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Guha Mazumder DN, Chakraborty AK, Ghose A, Gupta JD, Chakraborty DP, Dey SB, Chattopadhyay N. Chronic arsenic toxicity from drinking tubewell water in rural West Bengal. Bull World Health Organ. 1988;66(4):499–506.PubMedGoogle Scholar
  30. 30.
    Subramanian KS. Arsenic poisoning in West Bengal. Science. 1996;274:1287–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Sun GF, Dai GJ, Li FJ, Yamauchi H, Yoshida T, Aikawa H. The present situation of chronic arsenism and research in China. In: Chappell WR, Abernathy CO, Calderon RL, editors. Arsenic exposure and health effects. New York, NY: Elsevier; 1999. p. 123–6.CrossRefGoogle Scholar
  32. 32.
    Pi J, Yamauchi H, Kumagai Y, Sun GF, Yoshida T, Aikawa H, Hopenhayn-Rich C, Shimojo N. Evidence for induction of oxidative stress caused by chronic exposure of Chinese residents to arsenic contained in drinking water. Environ Health Perspect. 2002;110(4):331–6.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Yamauchi H, Aminaka Y, Yoshida K, Sun GF, Pi J, Waalkes MP. Evaluation of DNA damage in patients with arsenic poisoning: urinary 8-hydroxydeoxyguanine. Toxicol Appl Pharmacol. 2004;198:291–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Yoshida T, Yamauchi H, Sun GF. Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review. Toxicol Appl Pharmacol. 2004;198:243–52.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Pi J, Yamauchi H, Sun GF, Yoshida T, Aikawa H, Fujimoto W, Iso H, Cui R, Waalkes MP, Kumagai Y. Vascular dysfunction in patients with chronic arsenosis can be reversed by reduction of arsenic exposure. Environ Health Perspect. 2005;113:339–41.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Chakraborti D, Mukherjee SC, Pati S, Sengupta MK, Rahman MM, Chowdhury UK, Lodh D, Chanda CR, Chakraborti AK, Basu GK. Arsenic groundwater contamination in Middle Ganga Plain, Bihar, India: a future danger? Environ Health Perspect. 2003;111:1194–201.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Spallholz JE, Mallory Boylan L, Rhaman MM. Environmental hypothesis: is poor dietary selenium intake an underlying factor for arsenicosis and cancer in Bangladesh and West Bengal, India? Sci Total Environ. 2004;323:21–32.PubMedCrossRefGoogle Scholar
  38. 38.
    Berg M, Tran HC, Nguyen TC, Pham HV, Schertenleib R, Giger W. Arsenic contamination of groundwater and drinking water in Vietnam: a human health threat. Environ Sci Technol. 2001;35:2621–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Wai KM, Mar O, Kosaka S, Umemura M, Watanabe C. Prenatal heavy metal exposure and adverse birth outcomes in Myanmar: a birth-cohort study. Int J Environ Res Public Health. 2017;14(11):1339. Scholar
  40. 40.
    Berg M, Stengel C, Trang PTK, Hung VP, Sampson ML, Leng M, Samreth S, Fredericks D. Magnitude of arsenic pollution in the Mekong and Red River Deltas - Cambodia and Vietnam. Sci Total Environ. 2007;372:413–25.PubMedCrossRefGoogle Scholar
  41. 41.
    Ahsan H, Chen Y, Parvez F, Argos M, Hussain AI, Momotaj H, Levy D, Geen AV, Howe G, Graziano J. Health effects of arsenic longitudinal study (HEALS): description of a multidisciplinary epidemiologic investigation. J Expo Sci Environ Epidemiol. 2006;16:191–205.PubMedCrossRefGoogle Scholar
  42. 42.
    Chen Y, Parvez F, Gamble M, Islam T, Ahmed A, Argos M, Graziano JH, Ahsan H. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Toxicol Appl Pharmacol. 2009;239:184–92.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Gale CR, O’Callaghan FJ, Bredow M, Martyn CN. The influence of head growth in fetal life, infancy, and child- hood on intelligence at the ages of 4 and 8 years. Pediatrics. 2006;118:1486–92.PubMedCrossRefGoogle Scholar
  44. 44.
    Rahman A, Vahter M, Smith AH, Nermell B, Yunus M, Arifeen SE, Persson LÅ, Ekström EC. Arsenic exposure during pregnancy and size at birth: a prospective cohort study in Bangladesh. Am J Epidemiol. 2009;169:304–12.PubMedCrossRefGoogle Scholar
  45. 45.
    Tsai SY, Chou HY, The HW, Chen CM, Chen CJ. The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence. Neurotoxicology. 2003;24:747–53.PubMedCrossRefGoogle Scholar
  46. 46.
    Hamadani JD, Tofail F, Nermell B, Gardner R, Shiraji S, Bottai M, Arifeen SE, Huda SN, Vahter M. Critical windows of exposure for arsenic-associated impairment of cognitive function in pre-school girls and boys: a population-based cohort study. Int J Epidemiol. 2011;40:1593–604.PubMedCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Preventive MedicineSt. Marianna University School of MedicineKawasakiJapan

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