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Critical Evaluation of Cancer Risk from 2,4-D

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Reviews of Environmental Contamination and Toxicology

Part of the book series: Reviews of Environmental Contamination and Toxicology ((RECT,volume 167))

Abstract

2,4-D [(2,4-dichlorophenoxy)-acetic acid] is a widely used postemergent herbicide. It is structurally similar to indoleacetic acid (IAA), a naturally occurring plant hormone (see Fig.1). This similarity allows 2,4-D to mimic IAA and is the basis for its herbicidal action. The synthesis of 2,4-D was first reported in 1941 (ARC 1986I). In 1945, Dow Chemical Co. discovered that a 1:1 mixture of 2,4-D and 2,4,5-T [(2,4,5-trichlorophenoxy)-acetic acid] was a more effective herbicide than either of the two chemicals alone. The mixture was widely used thereafter and referred to as Agent Orange (Lilienfeld and Gallo 1989). Exposure to 2,4-D in the past may have more often been to a mixture of herbicides rather than 2,4-D alone. 2,4-D preparations before 1975 were often contaminated with TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) (IARC 1986;Johnson et al. 1992).

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References

  • Abdellatif AG, Preat V, Vamecq J, Nilsson J, Roberfroid M (1990) Peroxisome proliferation and modulation of rat liver carcinogenesis by 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, perfluorooctanoic acid and nafenopin. Carcinogenesis (Oxf) 11:1899–1902.

    CAS  Google Scholar 

  • Adams SL, Horvat ST, Irwin AE, Junkin RW, Koreman NM, Blakeey BR (1991) The effects of Tordon 202C exposure on urethan-induced lung adenoma formation in female CD-1 mice. Vet Hum Toxicol 33:209–211.

    PubMed  CAS  Google Scholar 

  • Adhikari N, Grover IS (1988) Genotoxic effects of some systemic pesticides: chromo-somal aberrations in bone marrow cells in rats. Environ Mol Mutagen 12:235–242.

    PubMed  CAS  Google Scholar 

  • Ahmed FE, Hart RW, Lewis NJ (1977) Pesticide induced DNA damage and its repair in cultured human cells. Mutat Res 42:161–174.

    PubMed  CAS  Google Scholar 

  • Arnold EK, Lovell RA, Beasley VR, Parker AJ, Stedelin JR (1991) 2,4-D toxicosis III: an attempt to produce 2,4-D toxicosis in dogs on treated grass plots. Vet Hum Toxicol 33:457–461.

    PubMed  CAS  Google Scholar 

  • Asp S, Riihimaki V, Hernberg S, Pukkala E (1994) Mortality and cancer morbidity of Finnish chlorophenoxy herbicide applicators: an 18-year prospective follow-up. Am J Ind Med 26:243–253.

    PubMed  CAS  Google Scholar 

  • Aspelin AL, Grube AH (1998) Pesticides industry sales and usage-1996 and 1997 market estimates. 733-R-98–001. Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency, Washington, DC.

    Google Scholar 

  • Bacher MA, Gibson GG (1988) Chlorophenoxyacid herbicides induce microsomal P-450 IVA1 (P-452) in rat liver. Chem Biol Interact 65:145–156.

    PubMed  CAS  Google Scholar 

  • Balarajan R, Acheson ED (1984) Soft tissue sarcomas in agriculture and forestry workers. J Epidemiol Community Health 38:113–116.

    PubMed  CAS  Google Scholar 

  • Barthel E (1981) Increased risk of lung cancer in pesticide-exposed male agricultural workers. J Toxicol Environ Health 8:1027–1040.

    PubMed  CAS  Google Scholar 

  • Blair A, Hoar Zahm S (1995) Overinterpretation of small numbers in the Dow 2,4-D cohort study (letter). J Occup Environ Med 37:126–127.

    PubMed  CAS  Google Scholar 

  • Blair A, Cantor KP, Zahm SH (1998) Non-Hodgkin’s lymphoma and agricultural use of the insecticide lindane. Am J Ind Med 33:82–87.

    PubMed  CAS  Google Scholar 

  • Blakely BR (1986) The effect of oral exposure to the N-butylester of 2,4-dichlorophen-oxyacetic acid on the immune response in mice. Int J Immunopharmacol 8:93–99.

    Google Scholar 

  • Blakley B (1997) Effect of roundup and tordon 202C herbicides on antibody production in mice. Vet Hum Toxicol 39:204–206.

    Google Scholar 

  • Blakely BR, Blakely PM (1986) The effect of prenatal exposure to the n-butylester of Cancer Risk From 2,4-D 27 2,4-dichloroacetic acid (2,4-D) on the immune response in mice. Teratology 33: 15–20.

    Google Scholar 

  • Blaldey BR, Gagnon JM, Rousseaux CG (1992) The effect of a commercial 2,4-D formulation on chemical-and viral-induced tumor production in mice. J Appl Toxicol 12:245–249.

    Google Scholar 

  • Blaldey BR, Yole MJ, Brousseau P, Boermans H, Foumler M (1998) Effect of 2,4dichlorophenoxyacetic acid, trifluralin and triallate herbicides on immune function. Vet Hum Toxicol 40:5–10.

    Google Scholar 

  • Bloemen LJ, Mandel JS, Bond GG, Pollock AF, Vitek RP, Cook RR (1993) An update of mortality among chemical workers potentially exposed to the herbicide 2,4-dichlorophenoxyacetic acid and its derivatives. J Occup Med 35:1208–1212.

    PubMed  CAS  Google Scholar 

  • Bond GG, Wetterstroem NH, Roush GJ, McLaren EA, Lipps TE (1988) Cause specific mortality among employees engaged in the manufacture, formulation, or packaging of 2,4-dichlorophenoxyacetic acid and related salts. Br J Ind Med 45:98–105.

    PubMed  CAS  Google Scholar 

  • Bond GG, Cartmill JB, Cook RR (1990) Investigation of excess cancer of other and unspecified sites among chemical workers (letter). Am J Ind Med 18:617–619.

    PubMed  CAS  Google Scholar 

  • Bongso TA, Basrur PK (1973) In vitro response of bovine cells to 2,4-dichlorophenoxyacetic acid. In Vitro 8:63.

    Google Scholar 

  • Brown LM, Dosemici M, Blair A, Burmeister L (1991) Comparability of data obtained from farmers and surrogate respondents on use of agricultural pesticides. Am J Epidemiol 134:348–355.

    PubMed  CAS  Google Scholar 

  • Cantor KP, Blair A, Everett G, Gibson R, Burmeister LF, Brown LM, Schumann L, Dick FR (1992) Pesticides and other agricultural risk factors for non-Hodgkin’s lymphoma among men in Iowa and Minnesota. Cancer Res 52:2447–2455.

    PubMed  CAS  Google Scholar 

  • Cantor KP, Blair A, Brown LM, Burmeister LF, Everett G (1993) Re: Pesticides and other agricultural risk factors for non-Hodgkin’s lymphoma among men in Iowa and Minnestoa (letter). Cancer Res 53:2421.

    PubMed  CAS  Google Scholar 

  • Carlo GL, Cole P, Miller AB, Munro IC, Solomon KR, Squire RA (1992) Review of a study reporting an association between 2,4-dichlorophenoxyacetic acid and canine malignant lymphoma: report of an expert panel. Regul Toxicol Pharmacol 16:245–252.

    PubMed  CAS  Google Scholar 

  • Charles JM, Bond DM, Jeffries TK, Yano BL, Stott WT, Johnson KA, Cunny HC, Wilson RD, Bus JS (1996a) Chronic dietary toxicity/oncogenicity studies on 2,4dichlorophenoxyacetic acid in rodents. Fundam Appl Toxicol 33:166–172.

    CAS  Google Scholar 

  • Charles JM, Cunny HC, Wilson RD, Bus JS (1996b) Comparative subchronic studies on 2,4-dichlorophenoxyacetic acid, amine and ester in rats. Fundam Appl Toxicol 33: 161–165.

    CAS  Google Scholar 

  • Charles JM, Dalgard DW, Cunny HC, Wilson RD, Bus JS (1996c) Comparative sub-chronic and chronic dietary toxicity studies on 2,4-dichlorophenoxyacetic acid, amine and ester in the dog. Fundam Appl Toxicol 29:78–85.

    CAS  Google Scholar 

  • Clausen M, Leier G, Witte I (1990) Comparison of the cytotoxicity and DNA-damaging properties of 2,4-D and U46 D Fluid (dimethylammonium salt of 2,4-D). Arch Toxicol 64:497–501.

    PubMed  CAS  Google Scholar 

  • Coggon D, Pannett B, Winter P (1991) Mortality and incidence of cancer at four factories making phenoxyherbicides. Br J Ind Med 48:173–178.

    PubMed  CAS  Google Scholar 

  • Crossen PE, Morgan WF, Horan JJ (1978) Cytogenetic studies of pesticide and herbicide sprayers. N Z Med J 88:192–195.

    PubMed  CAS  Google Scholar 

  • Dalager NA, Kang HK, Thomas TL (1995) Cancer mortality patterns among women who served in the military: the Vietnam experience. J Occup Environ Med 37:298–305.

    CAS  Google Scholar 

  • Edwards, MD, Pazzi, KA, Gumerlock, PH, Madewell, BR (1993) c-N-ras is activated infrequently in canine malignant lymphoma. Toxicol Pathol 21:288–291.

    PubMed  CAS  Google Scholar 

  • Epstein SS, Arnold E, Andrea J, Bass W, Bishop Y (1972) Detection of chemical muta-gens by the dominant lethal assay in the mouse. Toxicol Appl Pharmacol 23:288–325.

    PubMed  CAS  Google Scholar 

  • Eriksson M, Hardell L, Berg NO, Möller T, Axelson 0 (1981) Soft-tissue sarcomas and exposure to chemical substances: a case-referent study. Br J Ind Med 38:27–33.

    PubMed  CAS  Google Scholar 

  • Faustini A, Settimi L, Pacifici R, Fano V, Zuccaro P, Forastiere F (1996) Immunological changes among farmers exposed to phenoxy herbicides: preliminary observations. Occup Environ Med 53:583–585.

    PubMed  CAS  Google Scholar 

  • Fleming LE, Bean JA, Rudolf M, Hamilton K (1999) Cancer incidence in a cohort of licensed pesticide applicators in Florida. J Occup Environ Med 41:279–288.

    PubMed  CAS  Google Scholar 

  • Garry VF, Schreinemachers D, Harkins ME, Griffith J (1996) Pesticide appliers, bio-cides, and birth defects in rural Minnesota. Environ Health Perspect 104:394–399.

    PubMed  CAS  Google Scholar 

  • Gianessi LP, Puffer C (1991) Herbicide Use in the United States: National Summary Report. Resources for the Future, Washington, DC.

    Google Scholar 

  • Gianessi LP, Anderson JE (1995) Pesticide Use in US Crop Production. National Center for Food and Agricultural Policy, Washington, DC.

    Google Scholar 

  • Green L (1991) A cohort mortality study of forestry workers exposed to phenoxy acid herbicides. Br J Ind Med 48:234–238.

    PubMed  CAS  Google Scholar 

  • Greenwald P, Kovasznay B, Collins DN (1984) Sarcomas of soft tissues after Vietnam service. J Natl Cancer Inst 73:1107–1109.

    PubMed  CAS  Google Scholar 

  • Guidotti TL, Yoshida K, Clough V (1994) Personal exposure to pesticide among workers engaged in pesticide container recycling operations. Am Ind Hyg Assoc J 55:1154–1163.

    PubMed  CAS  Google Scholar 

  • Hansen WH, Quaife ML, Habermann RT, Fitzhugh OG (1971) Chronic toxicity of 2,4- dichlorophenoxyacetic acid in rats and dogs. Toxicol Appl Pharmacol 20:122–129.

    PubMed  CAS  Google Scholar 

  • Hardell L (1981) Relation of soft-tissue sarcoma, malignant lymphoma and colon cancer to phenoxy acids, chlorophenols and other agents. Scand J Work Environ Health 7: 119–130.

    CAS  Google Scholar 

  • Hardell L, Sandstrom A (1979) Case-control study: soft-tissue sarcoma and exposure to phenoxyacetic acids or chlorophenols. Br J Cancer 39:711–717.

    PubMed  CAS  Google Scholar 

  • Hardell L, Eriksson M, Lenner P, Lundgren E (1981) Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxyacetic acids: a case control study. Br J Cancer 43:169–176.

    PubMed  CAS  Google Scholar 

  • Hardell L, Eriksson M, Degerman A (1994) Exposure to phenoxyacetic acids, chlorophenols, or organic solvents in relation to histopathology, stage, and anatomical localization of non-Hodgkin’s lymphoma. Cancer Res 54:2386–2389.

    PubMed  CAS  Google Scholar 

  • Harris SA, Solomon KR (1992) Human exposure to 2,4-D following controlled activities on recently sprayed turf. J Environ Sci Health B 27:9–22.

    PubMed  CAS  Google Scholar 

  • Hayes HM, Tarone RE, Cantor KP, Jessen CR, McCurnin DM, Richardson RC (1991) Case-control study of canine malignant lymphoma: positive association with dog owner’s use of 2,4-dichlorophenoxyacetic acid herbicides. J Natl Cancer Inst 83: 1226–1231.

    PubMed  CAS  Google Scholar 

  • Hietanen E, Ahotupa M, Heinonen T, Hamalainen H, Kunnas T, Linnainmaa K, Mantyla E, Vainio H (1985) Enhanced peroxisomal 13-oxidation of fatty acids and glutathione metabolism in rats exposed to phenoxyacetic acids. Toxicology 34:103–111.

    PubMed  CAS  Google Scholar 

  • Hill EV, Carlisle H (1947) Toxicity of 2,4-dichlorophenoxyacetic acid for experimental animals. J Ind Hyg Toxicol 29:85–95.

    PubMed  CAS  Google Scholar 

  • Hoar SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R, Fraumeni JF Jr (1986) Cancer Risk From 2,4-D 29 Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 256: 1141–1147.

    PubMed  CAS  Google Scholar 

  • Hogstedt B, Kolnig A-M, Mitelman F, Skerfving S (1980) Cytogenetic study of pesticides in agricultural work (brief report). Heredity 92:177–178.

    CAS  Google Scholar 

  • IARC (1986) IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans; occupational exposures to chlorophenoxy herbicides. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. IARC, World Health Organization, Lyon, pp 357–407.

    Google Scholar 

  • IARC (1987) Chlorophenoxy herbicides. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. IARC, World Health Organization, Lyon, pp 151–160.

    Google Scholar 

  • Ibrahim MA, Bond GG, Burke TA, Cole P, Dost FN, Enterline PE, Gough M, Greenberg RS, Halperin WE, McConnell E, Munro IC, Swenberg JA, Zahm SH, Graham JD (1991) Weight of the evidence on the human carcinogenicity of 2,4-D. Environ Health Perspect 96:213–222.

    PubMed  CAS  Google Scholar 

  • Infante PF, Epstein SS, Newton WA (1978) Blood dycrasias and childhood tumors and exposure to chlordane and heptachlor. Scand J Work Environ Health 4:137–150.

    PubMed  CAS  Google Scholar 

  • Innes JRM, Ulland BM, Valerio MG, Petrucelli L, Fishbein L, Hart ER, Pallotta AJ, Bates RR, Falk HL, Gart JJ, Klein M, Mitchell I, Peters J (1969) Bioassay of pesticides and industrial chemicals for tumorigenicity in mice: a preliminary note. J Natl Cancer Inst 42:1101–1114.

    PubMed  CAS  Google Scholar 

  • Jacobi H, Witte I (1991) Synergistic effects of U46 D fluid (dimethylammonium salt of 2,4-D) and CuCl2 on cytotoxicity and DNA repair in human fibroblasts. Toxicol Lett 58:159–167.

    PubMed  CAS  Google Scholar 

  • Jenssen D, Renberg L (1976) Distribution and cytogenetic test of 2,4-D and 2,4,5-T phenoxyacetic acids in mouse blood tissues. Chem Biol Interact 14:291–299.

    CAS  Google Scholar 

  • Johnson ES, Parsons W, Weinberg CR, Shore DL, Mathews J, Patterson DG Jr, Needham LL (1992) Current serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in phenoxyacetic acid herbicide applicators and characterization of historical levels. J Natl Cancer Inst 84:1648–1653.

    PubMed  CAS  Google Scholar 

  • Johnson FE, Kugler MA, Brown SM (1981) Soft tissue sarcomas and chlorinated phenols. Lancet 2:40.

    CAS  Google Scholar 

  • Kale PG, Petty BT, Walker S, Ford JB, Dehkordi N, Tarasia S, Tasie BO, Kale R, Sohni YR (1995) Mutagenicity testing of nine herbicides and pesticides currently used in agriculture. Environ Mol Mutagen 25:148–153.

    PubMed  CAS  Google Scholar 

  • Kang HK, Weatherbee L, Breslin PP, Lee Y, Shepard BM (1986) Soft tissue sarcomas and military service in Vietnam: a case comparison group analysis of hospital patients. J Occup Med 28:1215–1218.

    PubMed  CAS  Google Scholar 

  • Kappas A (1988) On the mutagenic and recombinogenic activity of certain herbicides in Salmonella typhimurium and in Aspergillus nidulans. Mutat Res 204:615–621.

    PubMed  CAS  Google Scholar 

  • Kawashima Y, Katoh H, Nakajima S, Kozuka H, Uchiyama M (1984) Effects of 2,4dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid on peroxisomal enzymes in rat liver. Biochem Pharmacol 33:241–245.

    PubMed  CAS  Google Scholar 

  • Knopp D, Glass S (1991) Biological monitoring of 2,4-dichlorophenoxyacetic acid-exposed workers in agricultural and forestry. Int Arch Occup Environ Health 63:329–333.

    PubMed  CAS  Google Scholar 

  • Kogevinas M, Saracci R, Winkelmann R, Johnson E, Bertazzi PA, Bueno-de-Mesquita HB, Kauppinen T, Littorin M, Lynge E, Neuberger M, Pearce N (1993) Cancer inci-dence and mortality in women occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxins. Cancer Causes Control 4:547–553.

    PubMed  CAS  Google Scholar 

  • Kogevinas M, Kauppinen T, Winkelmann R, Becher H, Bertazzi PA, Bueno-de-Mesquita HB, Coggon D, Green L, Johnson E, Littorin M, Lynge E, Marlow DA, Mathews JD, Neuberger M, Benn T, Pannett B, Pearce N, Saracci R (1995) Soft tissue sarcoma and non-Hodgkin’s lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies. Epidemiology 6:396–402.

    PubMed  CAS  Google Scholar 

  • Kolberg, J, Helgeland, K, Jonsen, J, Tjeltveit, O (1970) Effect of phenoxyherbicides on mammalian cell cultures: a time-lapse cinemicrographic study. Acta Pharmacologica et Toxicologica 28:57.

    PubMed  CAS  Google Scholar 

  • Koli KM, Arteaga CL (1996) Complex role of tumor cell transforming growth factor (TGF)-ßs on breast carcinoma progression. J Mammal Gland Biol Neoplasia 1:373–380.

    CAS  Google Scholar 

  • Kross BC, Burnmeister LF, Ogilvie LK (1994) Mortality study among golf course superintendents. Golf Course Manage 62:49–56.

    Google Scholar 

  • Lathrop GD (1988) The epidemiology of Agent Orange and its associated dioxin. In: Young AL, Reggiani GM (eds) Agent Orange and Its Associated Dioxins: Assessment of a Controversy. Elsevier, New York, pp 92–113.

    Google Scholar 

  • Lawrence CE, Reilley AA, Quickenton P, Greenwald P, Page WF, Kuntz M (1985) Mortality patterns of New York State Vietnam veterans. Am J Public Health 75: 277–279.

    PubMed  CAS  Google Scholar 

  • Lilienfeld DE, Gallo MA (1989) 2,4-D, 2,4,5-T, and 2,3,7,8-TCDD: an overview. Epidemiol Rev 11:28–58.

    PubMed  CAS  Google Scholar 

  • Linnainmaa K (1983) Sister chromatid exchanges among workers occupationally exposed to phenoxy acid herbicides 2,4-D and MCPA. Teratog Carcinog Mutagen 3: 269–279.

    PubMed  CAS  Google Scholar 

  • Liu RCM, Hahn C, Hurtt ME (1996) The direct effect of hepatic peroxisome proliferators on rat Leydig cell function in vitro. Fundam Appl Toxicol 30:102–108.

    PubMed  CAS  Google Scholar 

  • Lorick KL, Ricci MS, Toscano WA (1995) Transforming growth factor-beta is increased in human breast cancer cells after exposure to organochlorine compounds (meeting abstract). Proc Annu Meet Am Assoc Cancer Res 36:A1012.

    Google Scholar 

  • Lynge E (1985) A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark. Br J Cancer 52:259–270.

    PubMed  CAS  Google Scholar 

  • Lynge E (1998) Cancer incidences in Danish phenoxy herbicide workers, 1947–1993. Environ Health Perspect 106:683–688.

    PubMed  Google Scholar 

  • Meister RT (1997) Pesticide dictionary; 2,4-D. In: Meister RT (ed) 1997 Farm Chemical Handbook. Meister Publishing, Willoughby, OH, pp C111–C112.

    Google Scholar 

  • Mills PK (1998) Correlation analysis of pesticide use data and cancer incidence rates in California counties. Arch Environ Health 53:410–413.

    PubMed  CAS  Google Scholar 

  • Mortelmans K, Haworth S, Speck W, Zeiger E (1984) Mutagenicity testing of Agent Orange Components and related chemicals. Toxicol Appl Pharmacol 75:137–146.

    PubMed  CAS  Google Scholar 

  • Munro IC, Carlo GL, Orr JC, Sund KG, Wilson RM, Kennepohl E, Lynch BS, Jablinske M, Lee NL (1992) A comprehensive, integrated review and evaluation of the scientific evidence relating to the safety of the herbicide 2,4-D. J Am Coll Toxicol 11: 559–664.

    CAS  Google Scholar 

  • Mustonen R, Kangas J, Vuojolahti P, Linnainmaa K (1986) Effects of phenoxyacetic acids on the induction of chomosome aberrations in vitro and in vivo. Mutagenesis 1: 241–245.

    PubMed  CAS  Google Scholar 

  • Mustonen R, Elovaara E, Zitting A, Linnainmaa K, Vainio H (1989) Effects of cial chlorophenolate, 2,3,7,8-TCDD, and pure phenoxyacetic acids on hepatic peroxisome proliferation, xenobiotic metabolism and sister chromatid exchange in the rat. Arch Toxicol 63:203–208.

    PubMed  CAS  Google Scholar 

  • Nagy Z, Mile I, Antoni F (1975) The mutagenic effect of pesticides on Escherichia coli WP2 try-. Acta Microbiol Acad Sci Hung 22:309–314.

    PubMed  CAS  Google Scholar 

  • Newell KW, Ross AD, Renner RM (1984) Phenoxy and picolinic acid herbicides and small-intestinal adenosarcoma in sheep. Lancet ii:1301–1304.

    Google Scholar 

  • Nishioka M, Hines C, Brinkman M, Burkholder H, Lewis RG (1998) Comparison of commercial vs homeowner application for transport of lawn-applied herbicide 2,4-D into homes. PB98–116536. NTIS, Springfield, Virginia.

    Google Scholar 

  • Olsen GW, Bodner KM (1996) The effects of the type of respondent on risk estimates of pesticide exposure in a non-Hodgkin’s lymphoma case-control study. J Agromed 3:37–49.

    Google Scholar 

  • Olsson H, Brandt L (1981) Non-Hodgkin’s lymphoma of the skin and occupational exposure to herbicides. Lancet 2:579.

    PubMed  CAS  Google Scholar 

  • Pearce N (1989) Phenoxy herbicides and non-Hodgkin’s lymphoma in New Zealand: frequency and duration of herbicide use (letter). Br J Ind Med 46:143–144.

    PubMed  CAS  Google Scholar 

  • Pearce N, Smith A, Howard J, Sheppard RA, Giles HJ, Teague C (1986) Non-Hodgkin’s lymphoma and exposure to phenoxyherbicides, chlorophenols, fencing work, and meat works employment: a case-control study. Br J Ind Med 43:75–83.

    PubMed  CAS  Google Scholar 

  • Phuong NTN, Hung BS, Schecter A, Vu DQ (1990) Dioxin levels in adipose tissues of hospitalized women living in the South of Vietnam in 1984–89 with a brief review of their clinical histories. Women Health 16:79–93.

    PubMed  CAS  Google Scholar 

  • Reuber MD (1983) Carcinogenicity and toxicity of 2,4-dichlorophenoxyacetic acid. Sci Total Environ 31:203–218.

    PubMed  CAS  Google Scholar 

  • Reynolds PM, Reif JS, Ramsdell HS, Tessari JD (1994) Canine exposure to herbicide-treated lawns and urinary excretion of 2,4-dichlorophenoxyacetic acid. Cancer Epidemiol Biomark Prey 3:233–237.

    CAS  Google Scholar 

  • Riihimäki V, Asp S, Hemberg S (1982) Mortality of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid herbicide aplicators in Finland. Scand J Work Environ Health 8:37–42.

    PubMed  Google Scholar 

  • Riihimäki V, Asp S, Pukkala E, Hemberg S (1983) Mortality and cancer morbidity among chlorinated phenoxyacid applicators in Finland. Chemosphere 12:779–784.

    Google Scholar 

  • Rubinstein C, Jone C, Trosko JE, Chang C-C (1984) Inhibition of intercellular communication in cultures of Chinese Hamster V79 cells by 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. Fundam Appl Toxicol 4:731–739.

    PubMed  CAS  Google Scholar 

  • Sandberg JA, Duhart HM, Lipe G, Biniendra Z, Slikker W Jr (1996) Distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) in fetal rats. J Toxicol Environ Health 49: 497–509.

    PubMed  CAS  Google Scholar 

  • Saracci R, Kogevinas M, Bertazzi P-A, Bueno De Mesquita BH, Coggon D, Green LM, Kauppinen T, L’Abbe KA, Littorin M, Lynge E, Mathews JD, Neuberger M, Osman J, Pearce N, Winkelmann R (1991) Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols. Lancet 338:1027–1032.

    PubMed  CAS  Google Scholar 

  • Sarma R, Jacobs J (1982) Thoracic soft-tissue sarcoma in Vietnam veterans exposed to Agent Orange. N Engl J Med 306:1109.

    PubMed  CAS  Google Scholar 

  • Sauerhoff MW, Braun WH, Blau GE, Gehring PJ (1977) The fate of 2,4-dichlorophen-oxyacetic acid (2,4-D) following oral administration to man. Toxicology 8:3–11.

    PubMed  CAS  Google Scholar 

  • Schop RN, Hardy MH, Goldberg MT (1990) Comparison of the activity of topically applied pesticides and the herbicide 2,4-D in two short-term in vivo assays of geno-toxicity in the mouse. Fundam Appl Toxicol 15:666–675.

    PubMed  CAS  Google Scholar 

  • Smith AH, Fisher DO, Giles HJ, Pearce N (1983) The New Zealand soft tissue sarcoma case-control study: interview findings concerning phenoxyacetic acid exposure. Chemosphere 12:565–571.

    CAS  Google Scholar 

  • Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO (1995) The E-Screen Assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect 103:113–122.

    PubMed  CAS  Google Scholar 

  • Sterling TD, Arundel AV (1986) Health effects of phenoxy herbicides. Scand J Work Environ Health 12:161–173.

    CAS  Google Scholar 

  • Sternberg SS (1992) Canine malignant lymphoma and 2,4-dichlorophenoxyacetic acid herbicides (letter). J Natl Cancer Inst 84:271.

    PubMed  CAS  Google Scholar 

  • Thomas TL, Kang HK, Dalager NA (1991) Mortality among women Vietnam veterans, 1973–1987. Am J Epidemiol 134:973–980.

    PubMed  CAS  Google Scholar 

  • Tindall JP (1985) Chloracne and chloracnegens. J Am Acad Dermatol 13:539–558. Turkula TE, Jalal SM (1985) Increased rates of sister chromatid exchanges induced by the herbicide 2,4-D. J Hered 76:213–214.

    Google Scholar 

  • Ulm L, Springer 0 (1994) Effect of prenatal and postnatal exposure to herbicide 2,4-D on the immunohaematopoietic mice system. Period Biol 96:499–503.

    CAS  Google Scholar 

  • USEPA (1996) Status of Chemicals in Special Review. 738-A-96–042. U.S. Environmental Protection Agency, Office of Prevention Pesticides and Toxic Substances, Washington, DC.

    Google Scholar 

  • USEPA (1997) Carcinogenicity peer review (4th) of 2,4-dichlorophenoxyacetic acid (2,4-D). U.S. Environmental Protection Agency Memorandum from Jeff Rowland and Esther Rinde (letter), Office of Pesticide Programs, Health Effects Division, Washington, DC.

    Google Scholar 

  • Vainio H, Linnainmaa K, Kahonen M, Nickels J, Hietanen E, Marniemi J, Peltonen P (1983) Hypolipidemia and peroxisome proliferation induced by phenoxyacetic acid herbicides in rats. Biochem Pharmacol 32:2775–2779.

    PubMed  CAS  Google Scholar 

  • Van DD (1984) Herbicides as a possible cause to liver cancer. In: Westing AH (ed) Herbicides in War; The Long Term Ecological and Human Consequences. Taylor & Francis, Philadelphia, pp 119–120.

    Google Scholar 

  • VAO (1996) Veterans and Agent Orange: Update 1996. National Academy Press, Washington, DC.

    Google Scholar 

  • Vin VD, Slozina NM, Nikitin AI (1990) Character of the estral cycle, rate of anovulation, chromosomal gametopathies and embryonal death in rats, when the females get 2,4dichlorofenoxyacetic acid (2,4-D) before pregnancy. Arkhiv Anatomii Gistologii I Embriologii 99:69.

    CAS  Google Scholar 

  • Vineis P, Terracini B, Ciccone G, Cignetti A, Colombo E, Donna A, Maffi L, Pisa R, Ricci P, Zanini E, Comba P (1986) Phenoxy herbicides and soft-tissue sarcomas in female rice weeders. A population based case-referent study. Scand J Work Environ Health 13:9–17.

    Google Scholar 

  • Vineis P, Faggiano F, Tedeschi M, Ciccone G (1991) Incidence rates of lymphomas and soft-tissue sarcomas and environmental measurements of phenoxy herbicides. J Natl Cancer Inst 83:362–363.

    PubMed  CAS  Google Scholar 

  • Warren JR, Lalwani ND, Reddy JK (1982) Phthalate esters as peroxisome proliferator carcinogens. Environ Health Perspect 45:35–40.

    PubMed  CAS  Google Scholar 

  • Weisenburger DD (1990) Environmental epidemiology of non-Hodgkin’s lymphoma in eastern Nebraska. Am J Ind Med 18:303–305.

    PubMed  CAS  Google Scholar 

  • Weisenburger D, Zahm S, Ward M, Babbitt P, Holmes F, Boysen C, Robel R, Saal R, Vaught J, Cantor K, Blair A (1991) Non-Hodgkin’s lymphoma associated with the agricultural use of herbicides; analysis by histologic type. Lab Invest 62:105A.

    Google Scholar 

  • WHO (1984) Environmental Health Criteria 29: 2,4-D. World Health Organization, Geneva.

    Google Scholar 

  • WHO (1989) Environmental Health Criteria 84: 2,4-D—Environmental Aspects. World Health Organization, Geneva.

    Google Scholar 

  • Wigle DT, Semenciw RM, Wilkins K, Riedel D, Ritter L, Morrison HI, Mao Y (1990) Mortality study of Canadian male farm operators: non-Hodgkin’s lymphoma mortality and agricultural practices in Saskatchewan. J Natl Cancer Inst 82:575–582.

    PubMed  CAS  Google Scholar 

  • Wiklund K, Dich J (1994) Cancer risks among female farmers in Sweden. Cancer Causes Control 5:449–457.

    PubMed  CAS  Google Scholar 

  • Wiklund K, Holm L (1986) Soft tissue sarcoma risk in Swedish agricultural and forestry workers. J Natl Cancer Inst 76:229–234.

    PubMed  CAS  Google Scholar 

  • Wiklund K, Dich J, Holm LE (1987a) Risk of malignant lymphoma in Swedish pesticide appliers. Br J Cancer 56:505–508.

    CAS  Google Scholar 

  • Wiklund K, Holm L, Dich J (1987b) Soft tissue sarcoma risk among agricultural and forestry workers in Sweden. Chemosphere 16:2107–2110.

    Google Scholar 

  • Witte I, Jacobi H, Juhl-Strauss U (1995) Correlation of synergistic cytotoxic effects of environmental chemicals in human fibroblasts with their lipophilicity. Chemosphere 31:4041–4049.

    PubMed  CAS  Google Scholar 

  • Woods JS, Polissar L (1989) Non-Hodgkin’s lymphoma among phenoxy herbicide-exposed farm workers in western Washington State. Chemosphere 18:401–406.

    Google Scholar 

  • Woods JS, Polissar L, Severson RK, Heuser LS, Kulander BG (1987) Soft tissue sarcoma and non-Hodgkin’s lymphoma in relation to phenoxyherbicide and chlorinated phenol exposure in western Washington. J Natl Cancer Inst 78:899–910.

    PubMed  CAS  Google Scholar 

  • Yoder J, Watson M, Benson WW (1973) Lymphocyte chromosome analysis of agricultural workers during extensive occupational exposure to pesticides. Mutat Res 21: 335–340.

    PubMed  CAS  Google Scholar 

  • Zahm SH, Weisenburger DD, Babbitt PA, Saal RC, Vaught JB, Cantor KP, Blair A (1990) A case-control study of non-Hodgkin’s lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska.Epidemiology 1:349–356.

    PubMed  CAS  Google Scholar 

  • Zahm S, Weisenburger DD, Saal RC, Vaught JB, Babbitt PA, Blair A (1993) The role of agricultural pesticide use in the development of non-Hodgkin’s lymphoma in women. Arch Environ Health 48:353–358.

    PubMed  CAS  Google Scholar 

  • Zahm SH (1997) Mortality study of pesticide applicators and other employees of a lawn care service company. J Occup Environ Med 39:1055–1067.

    PubMed  CAS  Google Scholar 

  • Zetterberg G, Busk L, Elovson R, Starec-Nordenhammar I, Ryttman H (1977) The influence of pH on the effects of 2,4-D (2,4-dichlorophenoxyacetic acid, Na salt) on Saccharomyces cerevisiae and Salmonella typhimurium. Mutat Res 42:3–18.

    PubMed  CAS  Google Scholar 

  • Zimmering S, Mason JM, Valencia R, Woodruff RC (1985) Chemical mutagenesis testing in Drosophila. II. Results of 20 coded compounds tested for the National Toxicology Program. Environ Mutagen 7:87–100.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Program on Breast Cancer and Environmental Risk Factors in New York State, Cornell University, 112 Rice Hall, Ithaca, NY, 14853, USA

    Renu Gandhi & Suzanne Snedeker

  2. Department of Cellular and Molecular Physiology, Division of Endocrinology, Diabetes and Metabolism, Penn State Medical College, Hershey Medical Center, Hershey, PA, USA

    Serge-Alain Wandji

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  1. Renu Gandhi
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  2. Serge-Alain Wandji
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  3. Suzanne Snedeker
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  1. Reviews of Environmental Contamination and Toxicology, 5794 E. Camino del Celador, Tucson, Arizona, 85750, USA

    George W. Ware

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Gandhi, R., Wandji, SA., Snedeker, S. (2000). Critical Evaluation of Cancer Risk from 2,4-D. In: Ware, G.W. (eds) Reviews of Environmental Contamination and Toxicology. Reviews of Environmental Contamination and Toxicology, vol 167. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-1156-3_1

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