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Carcinogenicity of Lindane, DDT, and 2,4-Dichlorophenoxyacetic Acid

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Carcinogenicity of Lindane, DDT, and 2,4-Dichlorophenoxyacetic Acid News Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid In June, 2015, 26 experts from immunosuppressive eff ects that can blood or adipose taken in adulthood; 13 countries met at the International operate in humans. however, the possible importance of Agency for Research on Cancer The insecticide DDT was classifi ed early-life exposure to DDT remains (IARC; Lyon, France) to assess the as “probably carcinogenic to humans” unresolved. Studies on non-Hodgkin carcinogenicity of the insecticides (Group 2A). DDT was used for the lymphoma and cancers of the liver lindane and 1,1,1-trichloro-2,2-bis(4- control of insect-borne diseases and testis provided limited evidence chlorophenyl)ethane (DDT), and the during World War 2; subsequently in humans for the carcinogenicity herbicide 2,4-dichlorophenoxyacetic it was widely applied to eradicate of DDT. acid (2,4-D). These assessments will malaria and also used in agriculture. Numerous studies in mice, rats, Published Online be published as Volume 113 of the Although most uses of DDT apart and hamsters (mainly oral admini- June 23, 2015 1 http://dx.doi.org/10.1016/ IARC Monographs. from disease vector control were stration) provided suffi cient evidence S1470-2045(15)00081-9 The insecticide lindane was banned from the 1970s, human in experimental animals for the For more on the IARC classifi ed as “carcinogenic to humans” exposure to DDT and to its metabolite carcinogenicity of DDT and its Monographs see http:// (Group 1). Lindane, the γ-isomer of 1,1-dichloro-2,2-bis(p-chlorophenyl) metabolites DDE and 1-chloro-4- monographs.iarc.fr/ hexachlorocyclohexane, has been ethylene (DDE) still occurs, mainly [2,2-dichloro-1-(4-chlorophenyl) Upcoming meetings as a consequence of biological ethyl]benzene (DDD). In mice, Oct 6–13, 2015, Volume 114: used extensively for insect control Red meat and processed meat in agriculture and for treatment of persistence leading to exposure 12 studies gave positive results, Feb 2–9, 2016, Volume 115: human ectoparasites. Occupational through diet. DDT is readily absorbed some for multiple tumour sites, Some industrial chemicals exposures have occurred among and is distributed in the body by with DDT consistently increasing the Monograph Working Group agricultural workers and pesticide lymphatic and blood circulation, with incidence of benign and malignant Members M Kogevinas (Spain)—Meeting applicators; however, the use of a preference for lipid-rich tissues. liver tumours; lymphoma incidence Chair; M L Larramendy lindane is now banned or restricted in Associations between cancer was also increased in three studies. (Argentina); B W Stewart most countries. Lindane is lipophilic, and exposure to DDT have been In rats, DDT increased the incidence of (Australia); T Sanderson (Canada); P Guénel (France); P Cocco (Italy); readily absorbed via all routes of investigated in more than 100 cohort benign and malignant liver tumours S Fukushima (Japan); ME Cebrian exposure, and distributes widely in and case-control studies from diverse in four studies. In hamsters, DDT Garcia [unable to attend]; the body. countries. Nested and population- signifi cantly increased the incidence L T Lopez Carrillo (Mexico); R Vermeulen (Netherlands); Epidemiological cohort and case- based case-control studies in China of adrenal cortex adenoma in two S Naidoo (South Africa); control studies of non-Hodgkin reported strong, dose-related studies. In rodents, the metabolites T Prapamontol (Thailand); lymphoma in several countries associations between liver cancer and DDE and DDD induced liver tumours F L Martin [unable to attend]; L Rushton (UK); M Alavanja; provided suffi cient evidence in blood DDT level after adjustment for in two studies each. M Bosland; R S Chhabra; W Chiu; 5–7 humans for the carcinogenicity potential confounders. No excess There is strong evidence that DDT A De Roos; R Herbert; M La Merrill; of lindane. The US Agricultural risk of liver cancer was reported in aff ects several mechanisms that D M Reif; D Roy; M T Smith; Health Study,2 a large prospective a historical cohort study8 of men can operate in humans. Immuno- K Thomas; M Wolff (USA) Invited Specialists cohort study with detailed exposure who sprayed DDT during a malaria- suppression has been consistently None assessment, reported statistically control campaign in Italy. In studies observed in numerous experimental Representatives signifi cant increases in non-Hodgkin on non-Hodgkin lymphoma, positive systems, including human cells in S Cazenave and C Queiroz lymphoma risk with increasing associations were reported in several vitro. DDT, DDD, and DDE increased Moreira, for the Brazilian Health occupational exposure to lindane. cohort and case-control studies in oxidative stress in human peripheral Surveillance Agency (ANVISA), Brazil; M-O Rambourg, for the 2,9,10 Population-based case-control studies North America and Europe, while blood mononuclear cells and French Agency for Food, in the mid-western USA and Canada other studies found no association.8 stimulated human colon cancer and Environment and Occupational also reported consistently positive Several case-control studies in the liver cancer cell proliferation in vitro Health and Safety, France; and D M Winn, for the National 3,4 associations. USA and Europe reported positive and in xenografted mice. Oestrogenic Cancer Institute, USA Suffi cient evidence in experimental associations between DDT or DDE eff ects and androgen-receptor Observers (non-voting) animals for the carcinogenicity of and testicular cancer, including a antagonism were consistently J S Bus, J E Goodman, and lindane was provided by several large case-control study11 nested in observed in numerous experimental S A McMaster, for the Industry Task Force II on 2,4-D Research studies of dietary administration a US military cohort. Although more systems including human cells in Data 12 in mice, with lindane consistently than 40 studies conducted since 1993 vitro. Anti-oestrogens blocked IARC/WHO Secretariat increasing the incidence of benign were reviewed, no clear asso ciation oestro genic eff ects of DDT in human L Benbrahim-Tallaa; V Bouvard; or malignant liver tumours. There is was found between breast cancer and breast cancer cells and in mice.13 R Brown; F El Ghissassi; Y Grosse; strong evidence that lindane causes DDT or DDE measured in samples of Progesterone receptor activation N Guha; K Z Guyton; M Korenjak; www.thelancet.com/oncology Vol 16 August 2015 891 News M Leon; D Loomis; H Mattock; was seen in vitro. Evidence of sex- The carcinogenicity of 2,4-D has 5 McGlynn KA, Abnet CC, Zhang M, et al. Serum K Straif; J Zavadil hormone disruption in exposed men been assessed in multiple rodent concentrations of 1,1,1-trichloro-2,2-bis(p- chlorophenyl)ethane (DDT) and 1,1-dichloro- For the Preamble to the IARC and women was unclear. bioassays and in an observational 2,2-bis(p-chlorophenyl)ethylene (DDE) and Monographs see http:// Since its introduction in 1945, 2,4-D study of pet dogs. In female mice, risk of primary liver cancer. J Natl Cancer Inst monographs.iarc.fr/ENG/ 2006; 98: 1005–10. Preamble/index.php has been widely used to control weeds single subcutaneous injections of the 6 Persson EC, Graubard BI, Evans AA, et al. For declarations of interests see in agriculture, forestry, and urban and isooctyl ester of 2,4-D increased the Dichlorodiphenyltrichloroethane and risk of http://monographs.iarc.fr/ENG/ 16 hepatocellular carcinoma. Int J Cancer 2012; residential settings. Occupational incidence of reticulum-cell sarcoma. Meetings/index.php 131: 2078–84. exposures to 2,4-D can occur during In male rats, 2,4-D in the diet induced 7 Zhao B, Shen H, Liu F, et al. Exposure to Of the working group members, organochlorine pesticides is an independent LR received an honorarium and manufacturing and application, while a positive trend in the incidence of rare 17 risk factor of hepatocellular carcinoma: travel expenses for providing the general population can be exposed brain astrocytomas. The Working a case-control study. J Expo Sci Environ advice on future epidemiological through food, water, dust, residential Group concluded that there was Epidemiol 2012; 22: 541–48. research to a Scientifi c Advisory application, and during spraying. limited evidence in experimental 8 Cocco P, Fadda D, Billai B, D’Atri M, Melis M, Group on Epidemiology of the Blair A. Cancer mortality among men European Crop Protection In humans, 2,4-D is eliminated largely animals for the carcinogenicity of occupationally exposed to Association and MTS has unchanged in the urine. 2,4-D due to methodological concerns dichlorodiphenyltrichloroethane. Cancer Res received payment for consulting Cancer risks associated with expo- regarding the positive studies, 2005; 65: 9588–94. and testimony from US law fi rms 9 Spinelli JJ, Ng CH, Weber JP, et al. and research support from the sure to 2,4-D have been evaluated although a substantial minority Organochlorines and risk of non-Hodgkin US Council for Education and in population-based case-control judged the evidence to be suffi cient. lymphoma. Int J Cancer 2007; 121: 2767–75. Research on Toxics. All other studies and in cohort studies of Mechanistic studies provided strong 10 Eriksson M, Karlsson M. Occupational and working group members declare other environmental factors and multiple no competing interests. The workers manufacturing and applying evidence that 2,4-D induces oxidative myeloma: a population based case-control representatives declare no pesticides. Due to the potential for stress that can operate in humans and study. Br J Ind Med 1992; 49: 95–103. 11 McGlynn KA, Quraishi SM, Graubard BI, competing interests. Of the confounding, studies involving moderate evidence that 2,4-D causes observers, JSB is a former Dow Weber JP, Rubertone MV, Erickson RL. Persistent organochlorine pesticides and risk Chemical Co employee, owns exposure to mixed herbicides or to immunosuppression, based on in-vivo of testicular germ cell tumors.
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