The history of arsenical pesticides and health risks related to the use of Agent Blue
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Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
Vladimir Bencko   

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
Ann Agric Environ Med. 2017;24(2):312–316
Arsenicals in agriculture. Beginning in the 1970s, the use of arsenic compounds for such purposes as wood preservatives, began to grow. By 1980, in the USA, 70% of arsenic had been consumed for the production of wood preservatives. This practice was later stopped, due to the US Environmental Protection Agency (EPA) ban of the arsenic-and chromium-based wood preservative chromated copper arsenate. In the past, arsenical herbicides containing cacodylic acid as an active ingredient have been used extensively in the USA, from golf courses to cotton fields, and drying-out the plants before harvesting. The original commercial form of Agent Blue was among 10 toxic insecticides, fungicides and herbicides partially deregulated by the US EPA in February 2004, and specific limits on toxic residues in meat, milk, poultry and eggs, were removed. Today, however, they are no longer used as weed-killers, with one exception – monosodium methanearsonate (MSMA), a broadleaf weed herbicide for use on cotton. Severe poisonings from cacodylic acid caused headache, dizziness, vomiting, profuse and watery diarrhea, followed by dehydration, gradual fall in blood pressure, stupor, convulsions, general paralysis and possible risk of death within 3–14 days.The relatively frequent use of arsenic and its compounds in both industry and agriculture points to a wide spectrum of opportunities for human exposure. This exposure can be via inhalation of airborne arsenic, contaminated drinking water, beverages, or from food and drugs. Today, acute organic arsenical poisonings are mostly accidental. Considerable concern has developed surrounding its delayed effects, for its genotoxic and carcinogenic potential, which has been demonstrated in epidemiological studies and subsequent animal experiments. Conclusions. There is substantial epidemiological evidence for an excessive risk, mostly for skin and lung cancer, among humans exposed to organic arsenicals in occupational and environmental settings. Furthermore, the genotoxic and carcinogenic effects have only been observed at relatively high exposure rates. Current epidemiological and experimental studies are attempting to elucidate the mechanism of this action, pointing to the question whether arsenic is actually a true genotoxic, or rather an epigenetic carcinogen. Due to the complexity of its effects, both options remain plausible. Its interactions with other toxic substances still represent another important field of interest.
Bencko V, Slámová A.Best practices for promoting farmers’ health: the case of arsenic history. J Public Health. 2007; 15: 279–288.
IARC (International Agency for Research on Cancer)Monographs, Supplement 4. Evaluation of the Carcinogenic Risks of Chemicals to Humans, Chemicals, Industrial Processes and Industries Associated with Cancer in Humans. International Agency for Research on Cancer. Lyon, 1982.
EPA (U.S. Environmental Protection Agency). Health Assessment Document for Inorganic Arsenic. Final Report. D. Jacobson-Kram, et al. Environmental Criteria and Assessment Office, EPA. Research Triangle Park, N.C, 1984.
ATSDR. Toxicological profile for arsenic. U.S. Dept. of Health and Human Services. Atlanta, Georgia, 2007.
Fowler BA. Biological and environmental effects of arsenic. Vol.6. Elsevier, Amsterdam, 1983.
Bencko V. Arsenic. In: Fishbein L, Furst A, Mehlman MA (Eds) Genotoxic and carcinogenic metals: Environmental and occupational exposure. Advances in Modern Environmental Toxicology. Princeton, New Jersey, Sci Publ, 1987; 11: 1–30.
Ishinishi N, Tsuchiya K, et al. Arsenic. In: Handbook on the Toxicology of Metals, Vol. 2, 2nded. (Friberg L, Nordberg GF, Vouk VB, eds.) Elsevier, Amsterdam, 1986.
Clarkson TW. Inorganic and Organometal Pesticides. In: Krieger RI, Handbook of pesticide toxicology, Agents. Academic Press, San Diego, 2001; pp. 1358–1428.
Rathus E, Stinton RG, Putnam JL. Arsine poisoning, country style. Med J Aus. 1979; 1: 163–6.
WSSA (Weed Science Society of America). 1974.
Stellman JM, Stellman SD, et al. The extent and patterns of usage of Agent Orange and other herbicides in Vietnam. Nature. 2003; 422: 681–687.
Young AL. The History, Use, Disposition and Environmental Fate of Agent Orange. Springer, NY, 2009. ISBN: 978-0-387-87485-2.
Buckingham WA Jr. Operation Ranch Hand: Herbicides in Southeast Asia. Air University Review, 1983. aureview/1983/Jul-Aug/buckingham.html.
Greenfield G. Agent Blue and the Business of Killing Rice. Zmag. 2004, June 18.
IOM (Committe to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides, Division of Health Promotion and DiseasePrevention, Institute of Medicine). Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam. National Academy Press, Washington DC, 1994.
Hood RD. Cacodylic acid: Agricultural Uses, Biological Effects, and Environmental Fate. Veterans Administration, Agent Orange Projects Office, Washington, DC, 1985.
Fishel FM. Pesticide Toxicity Profile: Arsenical Herbicides. PI-89. Pesticide Information Office, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida, 2005. (Revised in 2011).
Darrow RA, Irish KR, Minarik CD. Herbicides Used in Southeast Asia. Kelly AFB, TX, 1969. Technical Report SAOQ-TR-69-11078. 60 pp.
Mohr C. U.S. Spray Destroys Rice in Vietcong Territory. The New York Times, 21 Dec 1965.
EPA (U.S. Environmental Protection Agency). Organic arsenicals; Product Cancellation Order and Amendments to Terminate Uses (EPA-HQ-OPP-2009-0191; FRL-8437-7) 2009.
FDA (Food and Drug Administration). Arsanilic acid (21CFR558.62), pp. 413–414. 2008.
FDA (Food and Drug Administration). Roxarsone (21CFR558.530), pp. 500–503. 2008.
Patty FA. Industrial Hygiene and Toxicology, 2nd ed. John Wiley, NY, 1962.
WHO (World Health Organization). 12.8 Arsenic. In: 12. Chemical Fact Sheets. 2003
Berg M, Tran HC, et al. Arsenic contamination of groundwater and drinking water in Vietnam: a human health threat. Environ Sci Technol. 2001; 35: 2621–2626.
ACS (American Chemical Society). Northern Vietnam Drinking Water Contains Dangerous Arsenic Levels. ScienceDaily. 2001.
Ly TM. Arsenic Contamination in Groundwater in Vietnam: An Overview and Analysis of the Historical, Cultural, Economic, and Political Parameters in the Success of Various Mitigation Options. Pomona Senior Theses. Paper 41. 2012. http://scholarship.claremont.e....
OSHA (Occupational Safety and Health Administration). Occupational Safety and Health Guideline for Arsenic. U.S. Dept. of Labor 1996. healthguidelines/arsenic/recognition.html.
SBSG (Stanford Biology Study Group). The Destruction of Indochina. Science and Public Affairs. 1971; 27: 36–40.
Irvine L, Boyer IJ, DeSesso JM. Monomethylarsonic acid and dimethylarsinic acid: developmental toxicity studies with risk assessment. Birth Defects. Res B Dev Reprod Toxicol. 2006; 77: 53–68.
31., Inc. Cacodylic acid MSDS (Material Safety Data Sheet). 2005.
Hayes W Jr. Pesticides studied in man. Williams and Wilkins, Baltimore, 1982. ISBN-13: 978-0683038965.
Abernathy CO, Ohanian EV. Health effects of inorganic arsenic in drinking water. Proc. AWWA WQTC, Miami, Fla., Nov 7–11, 1993.
Petrick JS, Jagadish B, et al. Monomethylarsonous acid (MMA(III)) and arsenite: LD(50) in hamsters and in vitro inhibition of pyruvate dehydrogenase. Chem Res Toxicol. 2001; 14: 651–656.
Styblo M, et al. Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Arch Toxicol. 2000; 74: 289–299.
Vahter M. Effects of Arsenic on Maternal and Fetal Health. Annual Review of Nutrition. 2009; 29: 381–399.
Kapaj S, Peterson H, et al. Human health effects from chronic arsenic poisoning. A review. J Environ Sci Health. A Tox Hazard Subst Environ Eng. 2006; 41: 2399–428.
NJ (State of New Jersey). Right to Know Hazardous Substance Fact Sheet: Cacodylic Acid. 1999. (Revised in 2008).
Liebl B, Mückter H, et al. Influence of organic and inorganic arsenicals on glucose uptake in Madin-Darby canine kidney (MDCK) cells. Analyst. 1992; 117: 681–684.
IARC (International Agency for Research on Cancer). Arsenic and arsenic compounds. IARC Monogr Eval Carcinog Risk Hum. 2012; 100C: 41–93.
Kenyon EM, Hughes MF. A concise review of the toxicity and carcinogenicity of dimethylarsinic acid. Toxicology. 2001; 160: 227–236.
Spiewak R. Pesticides as a cause of occupational skin diseases in farmers. Ann Agric Environ Med. 2001; 8: 1–5.
Wei M, Wanibuchi H, et al. Urinary bladder carcinogenicity of dimethylarsinic acid in male F344 rats. Carcinogenesis. 1999; 20: 1873–1876.
Wanibuchi H, Hori T, et al. Promotion of rat hepatocarcinogenesis by dimethylarsinic acid: association with elevated ornithine decarboxylase activity and formation of 8-hydroxydeoxyguanosine in the liver. Jpn J Cancer Res. 1997; 88: 1149–1154.
Morikawa T, Wanibuchi H, et al. Promotion of skin carcinogenesis by dimethylarsinic acid in keratin (K6)/ODC transgenic mice. Jpn J Cancer Res. 2000; 91: 579–581.
Yamanaka K, Ohtsubo K, et al. Exposure to dimethylarsinic acid, a main metabolite of inorganic arsenics, strongly promotes tumorigenesis initiated by 4-nitroquinoline 1-oxide in the lungs of mice. Carcinogenesis. 1996; 17: 767–770.
EPA (U.S. Environmental Protection Agency). Cacodylic Acid: Decision Document. EPA, Office of Pesticide Programs, Washington, DC, 1981.
Antman K. Introduction: The History of Arsenic Trioxide in Cancer Therapy. The Oncologist. 2001; 6: 1–2.
Rogers EH, Chernoff N, Kavlock RJ. The teratogenic potential of cacodylic acid in the rat and mouse. Drug Chem Toxicol. 1981; 4: 49–61.