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Carcinogenicity of Tetrachlorvinphos, Parathion, Malathion, Diazinon, and Glyphosate

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Carcinogenicity of Tetrachlorvinphos, Parathion, Malathion, Diazinon, and Glyphosate News Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate In March, 2015, 17 experts from to the bioactive metabolite, paraoxon, aggressive cancers after adjustment for 11 countries met at the International is similar across species. Although other pesticides.9 In mice, malathion Agency for Research on Cancer (IARC; bacterial mutagenesis tests were increased hepatocellular adenoma Lyon, France) to assess the carcino­ negative, parathion induced DNA and or carcinoma (combined).10 In rats, genicity of the organophosphate chromosomal damage in human cells it increased thyroid carcinoma in pesticides tetrachlorvinphos, parathion, in vitro. Parathion markedly increased males, hepatocellular adenoma or malathion, diazinon, and glyphosate rat mammary gland terminal end carcinoma (combined) in females, (table). These assessments will be bud density.4 Parathion use has been and mammary gland adenocarcinoma published as volume 112 of the IARC severely restricted since the 1980s. after subcutaneous injection in Lancet Oncol 2015 1 4 Monographs. The insecticides malathion and females. Malathion is rapidly absorbed Published Online March 20, 2015 The insecticides tetrachlorvinphos diazinon were classifi ed as “probably and distributed. Metabolism to the http://dx.doi.org/10.1016/ and parathion were classifi ed as carcinogenic to humans” (Group 2A). bioactive metabolite, malaoxon, S1470-2045(15)70134-8 “possibly carcinogenic to humans” Malathion is used in agriculture, public is similar across species. Malaoxon For more on the IARC (Group 2B). The evidence from human health, and residential insect control. It strongly inhibits esterases; atropine Monographs see http:// monographs.iarc.fr studies was scarce and considered continues to be produced in substantial reduced carcinogenesis-related eff ects 4 inadequate. Tetrachlorvinphos induced volumes throughout the world. There in one study. Malathion induced DNA Upcoming meetings June 2–9, 2015, Volume 113: hepato cellular tumours (benign or is limited evidence in humans for the and chromosomal damage in humans, Some organochlorine malignant) in mice, renal tubule carcino genicity of malathion. Case- corroborated by studies in animals and insecticides and some tumours (benign or malignant) in control analyses of occupational in vitro. Bacterial mutagenesis tests chlorphenoxy herbicides 2 Oct 6–13, 2015, Volume 114: male mice, and spleen haemangioma exposures reported positive associa­ were negative. Compelling evidence Red meat and processed meat in male rats. Tetrachlorvinphos is tions with non-Hodgkin lymphoma supported dis ruption of hormone Monograph Working Group 5 6 7 a reactive oxon with affinity for in the USA, Canada, and Sweden, pathways. Hormonal eff ects probably Members esterases. In experimental animals, although no increased risk of non- mediate rodent thyroid and mammary A Blair (USA)—Meeting Chair; tetra chlorvinphos is systemically Hodgkin lymphoma was observed in gland proliferation. L Fritschi (Australia); J McLaughlin; C M Sergi (Canada); distributed, metabolised, and the large Agricultural Health Study Diazinon has been applied in G M Calaf (Chile); F Le Curieux eliminated in urine. Although bacterial cohort (AHS). Occupational use was agriculture and for control of home (Finland); I Baldi (France); mutagenesis tests were negative, associated with an increased risk and garden insects. There was limited F Forastiere (Italy); H Kromhout (Netherlands); A ‘t Mannetje tetrachlorvinphos induced genotoxicity of prostate cancer in a Canadian evidence for diazinon carcinogenicity (New Zealand); T Rodriguez in some assays (chromosomal damage case-control study8 and in the AHS, in humans. Positive associations [unable to attend] (Nicaragua); in rats and in vitro) and increased which reported a signifi cant trend for for non-Hodgkin lymphoma, with P Egeghy [unable to attend], cell proliferation (hyperplasia in rodents). Tetrachlorvinphos is banned Activity (current status) Evidence in humans Evidence Mechanistic evidence Classifi cation* in the European Union. In the USA, (cancer sites) in animals it continues to be used on animals, Tetrachlorvinphos Insecticide (restricted in Inadequate Sufficient ·· 2B the EU and for most uses including in pet fl ea collars. in the USA) For parathion, associations with Parathion Insecticide (restricted in Inadequate Sufficient ·· 2B cancers in several tissues were observed the USA and EU) in occupational studies, but the Malathion Insecticide (currently Limited (non- Sufficient Genotoxicity, oxidative stress, 2A† evidence in humans remains sparse. In used; high production Hodgkin lymphoma, infl ammation, receptor-mediated mice, parathion increased bronchiolo­ volume chemical) prostate) effects, and cell proliferation or death Diazinon Insecticide (restricted in Limited (non- Limited Genotoxicity and oxidative stress 2A† alveolar adenoma and/or carcinoma the USA and EU) Hodgkin lymphoma, in males, and lymphoma in females. In leukaemia, lung) rats, parathion induced adrenal cortical Glyphosate Herbicide (currently used; Limited (non- Sufficient Genotoxicity and oxidative stress 2A† 3 highest global production Hodgkin lymphoma) adenoma or carcinoma (combined), volume herbicide) malignant pancreatic tumours, and thyroid follicular cell adenoma in males, EU=European Union. *See the International Agency for Research on Cancer (IARC) preamble for explanation of classification system (amended January, 2006). †The 2A classification of diazinon was based on limited evidence of carcinogenicity in humans and experimental animals, and strong and mammary gland adenocarcinoma mechanistic evidence; for malathion and glyphosate, the mechanistic evidence provided independent support of the 2A classifi cation based on (after sub cutaneous injection in evidence of carcinogenicity in humans and experimental animals. females).4 Parathion is rapidly absorbed Table: IARC classifi cation of some organophosphate pesticides and distributed. Parathion metabolism www.thelancet.com/oncology Published online March 20, 2014 http://dx.doi.org/10.1016/S1470-2045(15)70134-8 1 News G D Jahnke; C W Jameson; indications of exposure–response of non-Hodgkin lymphoma. In male 3 National Toxicology Program. Bioassay of M T Martin; M K Ross; I Rusyn; trends, were reported by two large CD-1 mice, glyphosate induced a parathion for possible carcinogenicity. L Zeise (USA) Natl Cancer Inst Carcinog Tech Rep Ser 1979; multicentre case-control studies of positive trend in the incidence of a 70: 1–123. Invited Specialists occupational exposures.5,6 The AHS rare tumour, renal tubule carcinoma. A 4 Cabello G, Valenzuela M, Vilaxa A, et al. A rat C Portier (Switzerland) mammary tumor model induced by the Representatives reported positive associations with second study reported a positive trend organophosphorous pesticides parathion and 15 M E Gouze, for the French specifi c subtypes, which persisted for haemangiosarcoma in male mice. malathion, possibly through Agency for Food, Environment after adjustment for other pesticides, Glyphosate increased pancreatic acetylcholinesterase inhibition. Environ Health Perspect 2001; 109: 471–79. and Occupational Health and but no overall increased risk of non- islet-cell adenoma in male rats in two Safety (France); J Rowland, for 5 Waddell BL, Zahm SH, Baris D, et al. Agricultural 11 the US Environmental Protection Hodgkin lymphoma. Support for an studies. A glyphosate formulation use of organophosphate pesticides and the risk of non-Hodgkin’s lymphoma among male Agency (USA) increased risk of leukaemia in the AHS promoted skin tumours in an farmers (United States). Cancer Causes Control Observers was strengthened by a monotonic initiation-promotion study in mice. 2001; 12: 509–17. M K Boye Jensen, for Cheminova increase in risk with cumulative Glyphosate has been detected in 6 McDuffi e HH, Pahwa P, McLaughlin JR, et al. (Denmark); B Fervers, for the Non-Hodgkin’s lymphoma and specifi c pesticide Léon Bérard Centre (France); diazinon exposure after adjustment the blood and urine of agricultural exposures in men: cross-Canada study of E Giroux, for University for other pesticides. Multiple updates workers, indicating absorption. pesticides and health. Cancer Epidemiol Jean-Moulin Lyon 3 (France); from the AHS consistently showed an Soil microbes degrade glyphosate Biomarkers Prev 2001; 10: 1155–63. T Sorahan, for Monsanto 7 Eriksson M, Hardell L, Carlberg M, Akerman M. Company (USA); C Strupp, for increased risk of lung cancer with an to aminomethylphosphoric acid Pesticide exposure as risk factor for the European Crop Protection exposure–response association that (AMPA). Blood AMPA detection non-Hodgkin lymphoma including Association (Belgium); P Sutton, histopathological subgroup analysis. Int J Cancer was not explained by confounding by after poisonings suggests intestinal 2008; 123: 1657–63. for the University of California, San Francisco (USA) other pesticides, smoking, or other micro bial metabolism in humans. 8 Band PR, Abanto Z, Bert J, et al. Prostate cancer 12 risk and exposure to pesticides in British established lung cancer risk factors. Glyphosate and glyphosate formu­ IARC/WHO Secretariat Columbia farmers. Prostate 2011; 71: 168–83. L Benbrahim-Tallaa; R Carel; Nonetheless, this fi nding was not lations induced DNA and chromosomal 9 Koutros S, Beane, Freeman LE, et al. Risk of total F El Ghissassi; Sonia El-Zaemey; replicated in other populations. In damage in mammals, and in human and aggressive prostate cancer and pesticide use Y Grosse;
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