Review of 2,4-dichlorophenoxyacetic acid (2,4-D) epidemiology and toxicology.
The scientific evidence in humans and animals relevant to cancer risks, neurologic disease, reproductive risks, and immunotoxicity of 2,4-D was reviewed. Despite several thorough in vitro and in vivo animal studies, no experimental evidence exists supporting the theory that 2,4-D or any of its salts and esters damages DNA under physiologic conditions. Studies in rodents demonstrate a lack of oncogenic or carcinogenic effects following a lifetime dietary administration of 2,4-D. Epidemiologic studies provide scant evidence that exposure to 2,4-D is associated with soft tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, or any other cancer. Overall, the available evidence from epidemiologic studies is not adequate to conclude that any form of cancer is causally associated with 2,4-D exposure. There is no human evidence of adverse reproductive outcomes related to 2,4-D. The available data from animal studies of acute, subchronic, and chronic exposure to 2,4-D, its salts, and esters show an unequivocal lack of systemic toxicity at doses that do not exceed renal clearance mechanisms. There is no evidence that 2,4-D in any of its forms activates or transforms the immune system in animals at any dose. At high doses, 2,4-D damages the liver and kidney and irritates mucous membranes. Although myotonia and alterations in gait and behavioral indices are observed after overwhelming doses of 2,4-D, alterations in the neurologic system of experimental animals are not observed with the administration of doses in the microgram/kg/day range. It is unlikely that 2,4-D has any neurotoxic potential at doses below those required to induce systemic toxicity.
Garabrant
David H
DH
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor 48109-2029, USA. dhg@umich.edu
Philbert
Martin A
MA
D015084:2,4-Dichlorophenoxyacetic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D015197:Carcinogenicity Tests; D016022:Case-Control Studies; D015331:Cohort Studies; D004283:Dog Diseases / Q000139:chemically induced / Q000453:epidemiology; D004285:Dogs; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D006540:Herbicides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D006689:Hodgkin Disease / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007107:Immune System / Q000187:drug effects; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced / Q000453:epidemiology; D009152:Mutagenicity Tests; D009422:Nervous System Diseases / Q000139:chemically induced / Q000453:epidemiology; D012098:Reproduction / Q000187:drug effects; D012509:Sarcoma / Q000139:chemically induced / Q000453:epidemiology
D004785:Environmental Pollutants; D006540:Herbicides; D015084:2,4-Dichlorophenoxyacetic Acid