Since its introduction in the 1940s, the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been widely used to control weeds in agriculture, forestry, and urban and residential settings. According to documents obtained by public records requests, the U.S. Food and Drug Administration (FDA) forecast sharp increases in the levels of 2,4-D in American food after regulators approved new genetically modified 2,4-D tolerant crops that tolerate being sprayed directly with the herbicide. Use of 2,4-D is “expected to triple” after the introduction of these GMO crops, the agency said. The U.S. Environmental Protection Agency (EPA) has also approved Dow Agroscience’s “Enlist Duo,” a mixture of glyphosate and 2,4-D for use on genetically engineered corn, cotton and soybean seeds that Dow developed to tolerate the chemicals.
2,4-D use is “expected to triple” due to GMO crops
Both glyphosate and 2,4-D have been linked to cancer and other health problems, and there is little known about the synergistic toxicity of these chemicals. Chemical manufacturers are now seeking approval from the U.S. Department of Agriculture (USDA) for five-trait GMO maize seeds that are genetically engineered to tolerate 2,4-D, dicamba, glyphosate, glufosinate and quizaofop. See our fact sheets on glyphosate and dicamba.
Overview of 2,4-D
Scientific studies link 2,4-D to certain types of cancer, birth defects, immunosuppression and other health impacts in highly exposed populations including farmers, farmworkers and farming communities. More than 1,000 products containing 2,4-D are sold in the United States. The herbicide, which will kill many broadleaf weeds but not most grasses, comes in many forms, including liquids, dusts, and granules. Use of 2,4-D is so widespread that residues have been detected in surface and groundwater sources.
2,4-D was one of two active ingredients in the “Agent Orange” herbicide formulation used during the Vietnam War, though adverse health effects associated with Agent Orange have been blamed on a separate ingredient – 2,4,5-Trichlorophenoxyacetic acid, and its contaminant, dioxin.
In 2015 the World Health Organization’s International Agency for Research on Cancer (IARC) said a review of scientific literature showed that 2,4-D is “possibly” carcinogenic to humans. IARC said it based the classification on findings that while there was “inadequate evidence in humans and limited evidence in experimental animals” of ties between 2,4-D and cancer, epidemiological studies provided “strong evidence that 2,4-D induces oxidative stress … and moderate evidence that 2,4-D causes immunosuppression.”
The IARC classification contradicted a 2007 assessment by the U.S. Environmental Protection Agency (EPA), which said scientific data did not support a link between human cancer and 2,4-D exposure. The EPA states that 2,4-D “generally has low toxicity for humans.” However, many experts point out that U.S. regulations have not kept pace with scientific advances for understanding chemical risk.
The EPA allows 2,4-D to be used in the production of fruits and vegetables and is sprayed directly on some crops used for human and animal food. The U.S. Food and Drug Administration (FDA) has found residues of 2,4-D in food samples but asserts the pesticide traces people consume pose no health dangers. Documents obtained from the FDA through Freedom of Information Act (FOIA) requests show the government forecast sharp increases in the levels of 2,4-D in American food after regulators approved new 2,4-D tolerant crops developed by Dow AgroSciences that tolerate being sprayed directly with the herbicide.
In March of 2017, the Center for Food Safety and five other organizations sued the EPA over its approval of Dow’s new 2,4-D herbicide, designed to be used with 2,4-D-tolerant crops. The groups alleged the regulatory agency violated its duties under the Pesticide Act and violated its duties to protect endangered species. The group said the agency’s approval of Dow’s “Enlist Duo” product, which combines glyphosate and 2,4-D, was “part of a disturbing, industry-wide trend” in which crops are genetically engineered to withstand being sprayed with multiple pesticides. “While these GE crop systems initially provide a quick-fix way to kill weeds, the intensive spraying triggers rapid evolution of weed resistance to the chemicals. Just as overuse of antibiotics breeds resistant bugs and more antibiotics to kill them, so these GE crop systems drive a toxic spiral of increasing weed resistance and pesticide use.”
In July 2020 the U.S. Court of Appeals for the Ninth Circuit rejected the claims and ruled that Dow’s Enlist Duo could stay on the market. The court agreed with the petitioners that the EPA did not properly assess harm to the monarch butterflies associated with increased use of 2,4-D. But the court merely instructed the agency to review the risks to monarch butterflies.
Medical and scientific studies
A systematic review and meta-analysis of studies of associations between 2,4-D and NHL [non-Hodgkin lymphoma] found “new evidence for an association between NHL and exposure to the herbicide 2,4-D… Overall, in our analysis focused on the highest exposure group from each study, we identified a statistically significant association between 2,4-D exposure and increased RRs [relative risks] of NHL.” 2,4-dichlorophenoxyacetic acid (2,4-D) and risk of non-Hodgkin lymphoma: a meta-analysis accounting for exposure levels. Annals of Epidemiology, 2017.
Systematic review and meta-analyses of nearly three decades of epidemiological research on the relationship between non-Hodgkin lymphoma and occupational exposure to agricultural pesticides finds that “Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure.” Non-Hodgkin Lymphoma and Occupational Exposure to Agricultural Pesticide Chemical Groups and Active Ingredients: A Systematic Review and Meta-Analysis. International Journal of Environmental Research and Public Health, 2014.
A population-based case-control study in Italy found that “the positive association found between phenoxy herbicides exposures and NHL [non-Hodgkin lymphoma], when we restricted the analysis to the subjects who never used personal protective equipment, confirms previously reported associations…” Cancer and Pesticides: An Overview and Some Results of the Italian Multicenter Case–Control Study on Hematolymphopoietic Malignancies. Annals of the New York Academy of Sciences, 2006.
A population-based, case-control study in Nebraska found a “50% excess of NHL [non-Hodgkin lymphoma] associated with mixing or applying 2,4-D. The risk for NHL increased with the average frequency of use to more than threefold among those exposed more than 20 days per year.” A case-control study of non-Hodgkin’s lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska. Epidemiology, 1990.
Study of rates of adverse birth outcomes in Minnesota, Montana, North Dakota, and South Dakota found that “in rural, agricultural counties where wheat acreage occupies a larger percentage of the land and where use of chlorophenoxy herbicides is higher, anomalies of the circulatory/respiratory and musculoskeletal/integumentary system significantly increased.” Birth Malformations and Other Adverse Perinatal Outcomes in Four U.S. Wheat-Producing States. Environmental Health Perspectives, 2003.
Study of offspring of pesticide appliers in Minnesota found that “the rate of birth defects increased in…offspring born to the general population residing in high-use chlorophenoxy herbicide/fungicide regions…” Pesticide appliers, biocides, and birth defects in rural Minnesota. Environmental Health Perspectives, 1996.
Case-control study of breast cancer in California farm workers found “suggestive increases” in breast cancer risk “were seen for a phenoxyacetic acid herbicide, 2,4-D, an organophosphate, malathion, and an organochlorine insecticide, chlordane, ” and that the “risk associated with chemical use was stronger in younger women, those with early-onset breast cancer, and those diagnosed earlier.” Breast Cancer Risk in Hispanic Agricultural Workers in California. International Journal of Occupational and Environmental Health, 2013.
Nested case-control study of gastric cancer found that “Working in areas with high use of the phenoxyacetic acid herbicide 2,4-D was associated with gastric cancer…” Agricultural exposures and gastric cancer risk in Hispanic farm workers in California. Environmental Research, 2007.
Case-control study investigating the risk of parkinsonism in occupations found “Three individual compounds, the organochlorine 2,4-dichlorophenoxyacetic acid, the herbicide paraquat, and the insecticide and acaricide permethrin, were associated with more than a 3-fold increased risk of disease”. Occupation and Risk of Parkinsonism: A Multicenter Case-Control Study. Journal of the American Medical Association, 2009.
Amyotrophic lateral sclerosis
Large nationwide study published in the journal NeuroToxicology (December 2021) reports that “several neurotoxic pesticide exposures estimated using residential location were associated with statistically significant increased risk of ALS (amyotrophic lateral sclerosis). These include the herbicides 2,4-D and glyphosate, and the insecticides carbaryl and chlorpyrifos.” ALS is a progressive nervous system disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control. Pesticides applied to crops and amyotrophic lateral sclerosis risk in the U.S. NeuroToxicology, December, 2021.
Study of the association between pesticide use and thyroid diseases found “increased odds of hypothyroidism with ever-use of the herbicides 2,4-D, 2,4,5-T, 2,4,5-TP, alachlor, dicamba, and petroleum oil.” Hypothyroidism and pesticide use among male private pesticide applicators in the agricultural health study. Journal of Occupational and Environmental Medicine, 2013.
Sperm disorders/decreased male fertility
Study of the reproductive function of 32 male farmers exposed to 2,4-D found that “2,4-D can affect spermatogenesis in occupationally exposed farmers. The decrease of fertility in exposed subjects results from asthenospermia, necrospermia and teratospermia, frequently associated. The most important pathological aspects of the spermatogenesis of the exposed subjects are increase and permanence over time of abnormal spermatozoa.” Study of reproductive function in persons occupationally exposed to 2,4-dichlorophenoxyacetic acid (2,4-D). Mutation Research Letters, 1991.
Lipid/glucose metabolism/heart risk
Study on the toxicity of chlorophenoxy herbicides using linear regression found that “exposure to 2,4-D was associated with changes in biomarkers that, based on the published literature, have been linked to risk factors for acute myocardial infarction and type-2 diabetes.” Perturbation of lipids and glucose metabolism associated with previous 2,4-D exposure: a cross-sectional study of NHANES III data, 1988-1994. Environmental Health, 2010.
Study of blood samples from farmers found that “exposure to commercial 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) formulations may exert short term immunosuppressive effects.” Immunological changes among farmers exposed to phenoxy herbicides: preliminary observations. Occupational and Environmental Medicine, 1996.
Microbiome perturbations in mice
Study of sub-chronic low-dose 2,4-D exposure in a mouse model “revealed a distinct gut microbial community with profound changes in diverse microbial pathways including urea degradation, amino acid and carbohydrate metabolism in 2,4-D-treated mice. Moreover, the metabolomics results revealed that the metabolic profiles in treatment group were differentiated from control group in both fecal and plasma samples. Toxic effects on the host of 2,4-D at an occupationally relevant dose were observed indicated by decreased acylcarnitine levels in plasma. These findings indicated that 2,4-D can cause toxicity and substantially impact the gut microbiome in mice at occupationally relevant doses”. Subchronic low-dose 2,4-D exposure changed plasma acylcarnitine levels and induced gut microbiome perturbations in mice. Scientific Reports, 2019.
Other reports and fact sheets
Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services: Toxicological Profile for 2,4-Dichlorophenoxyacetic Acid (2,4-D), July 2020.
Natural Resources Defense Council: 2,4-D: The Most Dangerous Pesticide You’ve Never Heard Of.
Beyond Pesticides: Chemical Watch Factsheet 2,4-D
Pesticide Action Network: The risks of the herbicide 2,4-D
Journalism and opinion
EPA tosses aside safety data, says Dow pesticide for GMOs won’t harm people, by Patricia Callahan, Chicago Tribune. (12.8.15) “For use on its new genetically engineered corn and soybeans, Dow Chemical Co. is reviving 2,4-D, a World War II-era chemical linked to cancer and other health problems. If these crops are widely adopted, the government’s maximum-exposure projections show that U.S. children ages 1 to 12 could consume levels of 2,4-D that the World Health Organization, Russia, Australia, South Korea, Canada, Brazil and China consider unsafe.”
Congress questions EPA about Dow’s Enlist Duo pesticide risks, by Patricia Callahan, Chicago Tribune. (2.15.16) “When the EPA approved Enlist Duo in 2014, the agency tossed aside evidence of kidney lesions in lab rats that Dow’s own scientists said were caused by 2,4-D, clearing the way for children to be exposed to levels considered for decades to be unsafe, the Tribune investigation found.”
Reps. Blumenauer, DeFazio, Other Members Call on EPA to Reevaluate Risks of Powerful Herbicide Before Reapproved, Press Release. (2.12.16) “We were concerned to learn that … EPA dismissed a key study linking 2,4-D to kidney abnormalities based on one scientist’s analysis, and in doing so, effectively gave the green light for 41 times more of the chemical to enter the America diet than was previously allowed.”
Agent Orange in Your Backyard: The Harmful Pesticide 2,4-D, by Gina Solomon, The Atlantic. (2.24.12). “Newer science shows that it’s not just a cancer problem, but that this pesticide interferes with several essential hormones, thereby increasing the risks of birth defects and neurologic damage in children. Studies in Midwest wheat-growing areas (where 2,4-D is heavily used) have shown increased rates of certain birth defects, especially in male children, and lower sperm counts in adults.”
Last year it was dicamba, this year it’s 2,4-D, by Johnathan Hettinger, Midwest Center for Investigative Reporting. (3.29.19) “A volatile weed killer linked to cancer and endocrine issues will likely be sprayed on millions more acres of soybeans and cotton across the Midwest and South starting this year. In January, China approved imports of a new genetically modified soybean variety — Enlist E3 soybeans jointly made by Corteva Agriscience, a division of DowDupont and seed company MS Technologies — that can withstand the herbicide 2,4-D.”
What to know before you spray your lawn with pesticides, by Amanda Mascarelli, The Washington Post. (7.7.14) “Researchers are learning a great deal about how vulnerable children’s brains are to pesticides during fetal and early childhood development. “These delicate developmental processes are easily disrupted by very small doses of toxic chemicals that would be virtually harmless for an adult,” said Phil Landrigan, dean for global health and a professor of pediatrics at the Mount Sinai School of Medicine in New York.
Chemical spray damage results in record $7m negligence court payout, by Clint Jasper, ABC. (8.10.17) A grape grower in Australia was awarded $7 million in damages for losses caused by a neighbor’s negligent spraying of 2,4-D and other chemicals. “The chemical 2,4-D has been at the centre of a number of controversies, including in 2013 when it was revealed imported 2,4-D herbicides contained elevated levels of deadly dioxins.”
WHO unit finds 2,4-D herbicide ‘possibly’ causes cancer in humans, by Carey Gillam, Reuters. (6.22.15) “IARC’s findings on 2,4-D have been awaited by environmental and consumer groups that are lobbying U.S. regulators to tightly restrict its use, as well as by farm groups and others that defend 2,4-D as an important agent in food production that does not need more restrictions.”
Chemicals on our food: When “safe” may not really be safe, by Carey Gillam, Environmental Health News. (11.27.18) “Toxicologist Linda Birnbaum, who directs the U.S. National Institute of Environmental Health Sciences (NIEHS), has also raised concerns about pesticide dangers through exposures once assumed to be safe …. Last year she called for “an overall reduction in the use of agricultural pesticides” due to multiple concerns for human health, stating that “existing US regulations have not kept pace with scientific advances showing that widely used chemicals cause serious health problems at levels previously assumed to be safe.’”