2,4-D Technical Fact Sheet (2024)

• Chemical Class and Type
• Physical / Chemical Properties
• Uses
• Mode of Action
• Toxicity Classification
• Acute Toxicity
• Chronic Toxicity
• Endocrine Disruption
• Carcinogenicity
• Reproductive and Teratogenic Effects
• Fate in the Body
• Medical Tests and Monitoring
• Environmental Fate
• Ecotoxicity Studies
• Regulatory Guidelines

Laboratory Testing: Before pesticides are registered bythe U.S. EPA, they must undergo laboratory testing forshort-term (acute) and long-term (chronic) health effects.Laboratory animals are purposely given high enough dosesto cause toxic effects. These tests help scientists judge howthese chemicals might affect humans, domestic animals,and wildlife in cases of overexposure.

Chemical Class and Type:

• 2,4-D is an herbicide and secondarily a plant growth regulator.¹ Formulations includeesters, acids, and several salts, which vary in their chemical properties, environmentalbehavior, and to a lesser extent, toxicity.^2,3 The salt and ester forms are derivatives ofthe parent acid.² Unless otherwise stated, the discussion in this fact sheet will refer tothe acid form.
• The International Union of Pure and Applied Chemistry (IUPAC) chemical name forthe acid form is 2,4-dichlorophenoxyacetic acid, its Chemical Abstracts Service (CAS)registry number is 94-75-7, and the chemical family is the phenoxyacetic acid compounds.³
• The dimethyl-amine salt (DMA) and 2-ethylhexyl ester (EHE) forms account for approximately90-95% of the total global use.⁴ The acid form is low in solubility andherbicide formulations consist of more soluble forms of the chemical.² Products containing2,4-D frequently contain other herbicides as well.⁵
• Agent Orange, the herbicide widely used during the Vietnam war, contained 2,4-D.However, the controversy regarding health effects centered around the 2,4,5-T componentof the herbicide and its contaminant, dioxin.^6,7
• 2,4-D has been used in the United States since the 1940s, and it was evaluated for re-registration in 2005 by the UnitedStates Environmental Protection Agency (U.S. EPA).³ The U.S. EPAdetermined that 2,4-D was eligible for re-registration, but requiredcertain changes to labeled uses to mitigate risk.³ See thetext box on Laboratory Testing.

Physical / Chemical Properties:

Uses:

• 2,4-D is used for broadleaf weed control in agricultural and nonagricultural settings, and it is registered for use in both terrestrialand aquatic environments. Major sites include pasture and rangeland, residential lawns, roadways, and cropland.Crops treated with 2,4-D include field corn, soybeans, spring wheat, hazelnuts, sugarcane, and barley.³ Uses for productscontaining 2,4-D vary widely. Always read and follow the label when applying pesticide products.
• Approximately 46 million pounds are used each year in the United States, based on data from 1992-2000.³
• Signal words for products containing 2,4-D may range from Caution to Danger.¹⁰ The signal word reflects the combinedtoxicity of the active ingredient and other ingredients in the product. See the pesticide label on the product and refer tothe NPIC fact sheets on Signal Words and Inert or "Other" Ingredients.
• To find a list of products containing 2,4-D which are registered in your state, visit the websitehttp://npic.orst.edu/reg/state_agencies.html select your state then click on the link for "State Products."

Mode of Action:

Target Organisms

• 2,4-D is used on a wide variety of terrestrial and aquatic broadleaf weeds. It has little effect on grasses.¹² It appears towork by causing uncontrolled cell division in vascular tissue.¹² Abnormal increases in cell wall plasticity, biosynthesis ofproteins, and production of ethylene occur in plant tissues following exposure, and these processes are responsible foruncontrolled cell division.^3,12
• The ester forms of 2,4-D penetrate foliage, whereas plant roots absorb the salt forms.¹² 2,4-D appears to be similar in actionto other auxin-type herbicides.¹²

Non-target Organisms

• The modes of toxicity to animals from the acid, ester and salt forms of 2,4-D are similar. The primary exception is that thesalt and acid forms can be extreme eye irritants.³ 2,4-D is actively secreted by the proximal tubules of the kidney, and toxicityappears to result when renal clearance capacity is exceeded.³ Dose-dependent toxic effects include damage to theeye, thyroid, kidney, adrenals, and ovaries or testes.³ In addition, researchers have observed neurotoxicity, reproductivetoxicity, and developmental toxicity.³ Chlorophenoxy herbicides exhibit a variety of mechanisms of toxicity, includingdose-dependent cell membrane damage leading to central nervous system toxicity,13 interference with cellular metabolisminvolving acetyl-coenzyme A (CoA),¹³ and uncoupling of oxidative phosphorylation due to either the disrupted CoAactivity or cellular membrane damage.¹³

Acute Toxicity:

Oral

• LD₅₀ values range from 639 mg/kg to 1646 mg/kg in rats depending on the chemical form of 2,4-D utilized in the study.³Researchers found that 2,4-D was more toxic for mice, reporting an LD₅₀ of 138 mg/kg.¹ All chemical forms for 2,4-D areconsidered low in toxicity¹¹ for acute oral exposure based on tests with rats.³ See the text boxes on Toxicity Classification and LD₅₀/LC₅₀.

LD₅₀/LC₅₀: A commonmeasure of acute toxicity is the lethal dose (LD₅₀) orlethal concentration (LC₅₀) that causes death (resultingfrom a single or limited exposure) in 50 percent of the treatedanimals. LD₅₀ is generally expressed as the dose inmilligrams (mg) of chemical per kilogram (kg) of bodyweight. LC₅₀ is often expressed as mg of chemical pervolume (e.g., liter (L)) of medium (i.e., air or water) the organismis exposed to. Chemicals are considered highly toxic when theLD₅₀/LC₅₀ is small and practically non-toxicwhen the value is large. However, the LD₅₀/LC₅₀does not reflect any effects from long-term exposure (i.e., cancer,birth defects or reproductive toxicity) that may occur at levels belowthose that cause death.

Dermal

• Acute dermal LD₅₀s ranged from 1829 mg/kg to greater than2000 mg/kg in rabbits depending on the chemical form of 2,4-D.All chemical forms of 2,4-D are considered low in toxicity foracute dermal exposure based on studies using rabbits.³
• The acid and salt forms of 2,4-D are highly toxic to eye tissue,causing severe eye irritation. This is reflected in the signal wordof the formulated product. The ester forms are not consideredeye irritants, and have Iow to very low ocular toxicity.³
• The ester and salt forms of 2,4-D are considered slight skin irritants.³

Inhalation

• All chemical forms of 2,4-D are of low to very low toxicity via inhalation based on studies using rats. Acute inhalation LC₅₀sfor rats ranged from 0.78 mg/L to greater than 5.4 mg/L depending on the chemical form.³ Most forms of 2,4-D are verylow in toxicity, and the parent acid and TIPA salt forms are low in toxicity.³

Signs of Toxicity - Animals

• Dogs fed 2,4-D exhibited myotonia, vomiting, and weakness; dogs are more sensitive to chlorophenoxy acid herbicidesthan other animals.¹⁴ In addition, dogs and cats have displayed inappetance, anorexia, ataxia, salivation, diarrhea, lethargy,and convulsions following exposure to 2,4-D, which may include eating treated grass¹⁵ although the potential for this isunclear.¹⁶ Rats demonstrated incoordination, central nervous system depression and muscular weakness following acuteoral dosing.^3,17 Biochemical analysis of rat tissues suggested hepatic and muscle damage following acute, subchronic, andchronic oral exposures.¹⁷

Signs of Toxicity - Humans

• No occupational studies were found reporting signs or symptoms following exposure to 2,4-D under normal usage.
• Symptoms of acute oral exposure to 2,4-D include vomiting, diarrhea, headache, confusion, aggressive or bizarre behavior.A peculiar odor is sometimes noted on the breath. Skeletal muscle injury and renal failure may also occur.¹⁸ Systemic toxicityis mainly associated with suicide attempts.¹⁸
• Symptoms following dermal exposure may include irritation, and inhalation exposure may lead to coughing and burningsensations in the upper respiratory tract and chest.¹⁸ Prolonged exposure may result in dizziness.¹⁸ Chlorophenoxycompounds such as 2,4-D are quickly absorbed when swallowed, but absorption from dermal or inhalation exposure islow.^13,18
• Case reports and observational studies provide the majority of information regarding the toxicological effects of 2,4-Din incidents involving human poisonings. Researchers compiled the medical cases of 69 people who ingested 2,4-D andother chlorophenoxy herbicides; 23 of these patients died.¹³ Ingestion led to vomiting, abdominal pain, diarrhea, and developmentof hypotension.¹³ Peripheral neuromuscular effects including muscle twitching, weakness, and loss of tendonreflexes have been reported.¹³ Neuromuscular effects have lasted several weeks to months and have been permanent insome cases.¹³
• Always follow label instructions and take steps to minimize exposure. If any exposure occurs, be sure to follow the First Aidinstructions on the product label carefully. For additional treatment advice, contact the Poison Control Center at 1-800-222-1222. If you wish to discuss an incident with the National Pesticide Information Center, please call 1-800-858-7378.

Chronic Toxicity:

Animals

• Subchronic oral exposure to 2,4-D caused damage to the eye, thyroid,kidney, adrenals, and the ovaries and testes of laboratory animals.^3,19 Asubchronic NOEL was established at 15 mg/kg/day based on studies inrats.¹⁹ See the text box on NOAEL, NOEL, LOAEL, and LOEL.
• The chronic toxicity NOEL in rats and mice was determined to be 5 mg/kg/day in two-year studies.^12,20 The maximum tolerateddose in the two-year rat study was 150 mg/kg/day in male rats and 75 mg/kg/day in females.²⁰ Additional NOEL andNOAEL doses were 15 mg/kg for rats in a 90-day study, and 1 mg/kg for dogs in a 12-month study, respectively.^12,21 Rabbitsexhibited toxicity following dosing with either acid, salt, or ester forms of 2,4-D at doses of 30 mg/kg/day or greater.⁴Chronic NOAELs and LOELs in dogs, however, varied for different parameters studied and by chemical form.²¹
• Rats showed no outward signs of toxicity following exposure to 200 mg/L of 2,4-D in drinking water for 30 and 100 days,but biochemical analysis suggested hepatic and muscle damage.¹⁷
• Researchers fed rats 2,4-D at doses of 1, 15, 100, and 300 mg/kg/day acid equivalents (ae). Changes in blood and thyroidparameters, organ weight ratios, and body weight gain were noted at 100 and 300 mg/kg/day doses.¹⁹ Chronic toxicity inthe eye, kidney, thyroid and liver of the rat were similar to effects found in subchronic studies.²⁰ Eye lesions were associatedonly with high doses of 150 mg/kg/day.²⁰

Humans

• No human data were found on chronic effects of 2,4-D other than epidemiological studies of cancer occurrence. Althoughpesticide use has been linked to Parkinson's disease and to respiratory disease in farmers, 2,4-D was not implicated in anyrelationships between pesticide exposure and subsequent disease.^22,23 See the Carcinogenicity section below for moreinformation on 2,4-D and cancer in humans. See the text box on Exposure.

Exposure: Effects of 2,4-D on human health and the environment depend on how much2,4-D is present and the length and frequency of exposure. Effects also depend on the healthof a person and/or certain environmental factors.

Endocrine Disruption:

• Because 2,4-D has demonstrated toxic effects on the thyroid and gonads following exposure, there is concern over potentialendocrine-disrupting effects.³ 2,4-D is included in the U.S. EPA June 2007 Draft List of Chemicals for Tier 1 Screening.²⁴

Carcinogenicity:

Animals

• No oncogenic effects were observed in rats or mice following 2 years of dietary exposure of 2,4-D with concentrationsranging from 5-150 mg/kg/day or 5-300 mg/kg/day, respectively.²⁰ Similarly, researchers did not observe immunotoxic oroncogenic responses in dogs dosed with 1.0-7.5 mg/kg/day for either 13 weeks or 1 year.²¹
• A case-control study in companion dogs concluded that there was a "modest association" between malignant lymphomain the dogs and the use of 2,4-D in their owners' yards after accounting for other home and yard pesticide use.²⁵ Otherinvestigators have questioned the epidemiological association reported in that study.^5,26
• Overall, there has been no consistent association between exposure to 2,4-D and tumor induction in animals.²⁷ More recently,non-cytotoxic concentrations of 2,4-D were correlated to DNA damage and altered expression of some genes inhamster embryo cells.²⁸

Humans

• The U.S. EPA evaluated 2,4-D for carcinogenic effects in 1988, 1992, and again in 2004. Each evaluation has concluded that"the data are not sufficient to conclude that there is a cause and effect relationship between exposure to 2,4-D and non-Hodgkin's Lymphoma." 2,4-D was categorized as "Group D - not classifiable as to human carcinogenicity" in 2004.³ Seethe text box on Cancer.

  Cancer: Government agencies in the United States and abroad have developed programs to evaluate thepotential for a chemical to cause cancer. Testing guidelines and classification systems vary. To learn moreabout the meaning of various cancer classification descriptors listed in this fact sheet, please visit theappropriate reference, or call NPIC.

• The International Agency for Research on Cancer (IARC), had not assigned 2,4-D a cancer rating as of June 2008. However,in 1987, IARC placed the family of chlorophenoxy herbicides in Group 2B, possibly carcinogenic to humans.²⁹
• A discussion of the history of classification decisions regarding the carcinogenicity of 2,4-D has been published. A confoundingfactor in determining the carcinogenicity of 2,4-D is the frequent simultaneous exposure of workers to 2,4-D inaddition to 2,4,5-T and its contaminant TCDD (dioxin), or to other herbicides. However, other work examining incidents ofexposure to 2,4-D without simultaneous exposure to 2,4,5-T has found some association between 2,4-D and non-Hodgkin'slymphoma.²⁶
• Although the free acid form of 2,4-D did not damage chromosomes, there is limited evidence that commercial formulationsmay have the potential to do so.²⁷ Overall, evidence for mutagenicity has been inconsistent.^26,27,30

Reproductive or Teratogenic Effects:

Animals

• Teratogenic effects were not observed in mice, rats, or rabbits unless the excretion capacity of the mother was overwhelmedfollowing oral exposure to 2,4-D or its salt and ester forms.^4,26 Reduced fetal viability was observed in hamstersfollowing maternal dosing at 40 mg/kg/day during pregnancy, although effects did not follow a dose-response relationship.³¹
• Fetal abnormalities were observed in rats following oral doses of 90 mg/kg/day or greater beginning at fertilization; thesedoses were toxic to the mothers as well.⁴ A NOEL of 25 mg/kg/day was derived for fetal rats in one study, and a NOAELof 12.5 mg/kg/day for the mothers and a developmental NOAEL of 50 mg/kg/day for the young were derived in anotherstudy.⁷ The overall maternal NOEL in rats was determined to be 8-17 mg/kg/day and overall developmental NOEL was 30mg/kg/day 2,4-D acid equivalents.⁴
• Rabbit fetuses were unaffected at doses below 40 mg/kg/day administered to the dams although extra ribs were formedat doses above this threshold.⁴ In rabbits, the developmental NOEL was 30 mg/kg/day 2,4-D acid equivalents.⁴

Humans

• No experimental data are available regarding the effects of 2,4-D exposure on reproduction or development in humans.There are some reports of reproductive effects following occupational exposure to chlorophenoxy herbicides,⁷ includingreduced sperm motility and viability following occupational exposure. Although motility and viability recovered over aperiod of several months, malformations were still present.³² Exposure to multiple pesticides in epidemiological studiesmake inference difficult.²⁶

Fate in the Body:

Absorption

• The greatest absorption rates in humans are from oral exposure, with much less absorption occurring following dermal orinhalation exposures.¹⁸ Absorption rates following ingestion are dose-dependent in laboratory animals, with larger dosespersisting in the gastrointestinal tract for longer periods of time.⁷ In humans, plasma levels following 5 mg/kg oral ingestionpeaked between 4-24 hours post-exposure.⁷
• Dermal exposure is considered the most likely route of exposure during product use.⁷ Absorption of 2,4-D across the skinoccurs more slowly and is less complete, and varies by chemical form, product formulation, species, and site of application.⁷Dermal absorption may be increased significantly with application of some sunscreens, insect repellents, or by alcoholconsumption, as demonstrated in laboratory studies using rats and mice.^33,34,35 Hairless mouse skin absorbed 39% of a100 μL dose in 24 hours.³⁴

Distribution

• In laboratory animals, the primary target organs for 2,4-D toxicity were the eye, thyroid, kidney, adrenal glands, and ovariesor testes following subchronic oral exposure at doses above the threshold of saturation for renal clearance.³ Biochemicalchanges suggested that liver and muscle damage occurred in rats at acute, subchronic, and chronic doses.¹⁷
• In humans, 2,4-D has a wide volume of distribution due to its water solubility, but it does not accumulate in any tissue.⁷

Metabolism

• Metabolism of 2,4-D is minimal in humans, with nearly all of it excreted unchanged as the parent compound.^7,36 The remainderis excreted as an unspecified 2,4-D conjugate.³⁷
• In animals, little 2,4-D is metabolized prior to excretion. Up to 3.2% of the applied dose in rats was excreted as an unspecifiedpolar metabolite.²⁶ In sheep and cattle, muscle, liver, kidney, and fat tissue contained the metabolite 4-chlorocatechol.38 Dogs must metabolize the parent compound prior to excretion, due to their reduced ability to excrete organicacids.³⁹
• No reactive intermediate metabolic products for 2,4-D have been identified in any species.²⁶

Excretion

• In humans, 2,4-D is rapidly excreted from the body, primarily in the urine.⁷ Much of the compound appears to be eliminatedunchanged, although some 2,4-D is eliminated from the body as a conjugate.³⁷ The percent of original dose excreted asa polar, acid-hydrolyzable metabolite was 4.8-27.0%.²⁶ The elimination half-life from blood plasma in humans orally dosedwith 5 mg/kg of 2,4-D was 11.6 hours.³⁷ These human volunteers excreted more than 75% of 2,4-D in their urine within 96hours of oral dosing.³⁶ Concentrations in blood plasma paralleled concentrations excreted in urine.³⁶ Some 2,4-D may beexcreted in perspiration but this process appears to occur more slowly compared with urinary excretion.⁷
• Excretion of 2,4-D in animals depends on the species, formulation, and dose.⁴⁰ In rats, elimination of orally administereddoses of 5 and 50 mg/kg 2,4-D took 24 hours, and the urine was composed almost entirely of unmetabolized 2,4-D.³⁹
• Dogs excreted a 5 mg/kg oral dose primarily in their urine with minor amounts detected in feces.³⁹ Dogs dosed with 50mg/kg excreted equal amounts in urine and feces and excretion was incomplete at 120 hours post-dose.³⁹ Because dogsappear to be deficient in their ability to excrete organic acids, 2,4-D must be metabolized prior to excretion.³⁹ Dogs orallydosed with 2,4-D excreted the parent compound, several conjugates and one unidentified compound in their urine.³⁹
• Excretion of 2,4-D in urine is dose-dependent but nonlinear, with percent excreted in urine declining at higher doses.⁷ Inall of the species of animals studied, 2,4-D is excreted quickly and almost entirely in the urine.⁷

Medical Tests and Monitoring:

• Biomarkers of exposure to 2,4-D have been reported in the scientific literature.⁴¹ Scientists used high-performance liquidchromatography with tandem mass spectrometry to detect 2,4-D in urine.^41,42
• Laboratory testing for 2,4-D is not widely available to physicians.
• 2,4-D was detected at low concentrations in urine samples collected from all age groups in a large study of the Americanpublic.⁴¹ However, how these residues may affect human health is presently not clear,⁴¹ and the relationship between exposurelevel and biomarker is unknown.⁴³

Environmental Fate:

Soil

• 2,4-D amine salts and esters are not persistent under most environmentalconditions.³ Typically, the ester and amine forms of 2,4-D areexpected to degrade rapidly to the acid form.³ Soil half-life valueshave been estimated at 10 days for the acid, diethylamine salt, andester forms.⁴⁴ Another study estimated a soil half-life for the esterform EHE ranging from 1-14 days with a median half-life of 2.9 days.³In aerobic mineral soils, a half-life of 6.2 days was estimated.³ A granularformulation of the BEE form was detected in aquatic sedimentsfor 186 days post-application, perhaps due to either the formulationor slow de-esterification of the sediment-bound chemical.³ See thetext box on Half-life.
• Microbial degradation of 2,4-D in soil involves hydroxylation, cleavage of the acid side-chain, decarboxylation, and ringopening.¹ The ethyl hexyl form of the compound is rapidly hydrolyzed in soil and water to form the 2,4-D acid.¹ Other comparativestudies demonstrated that ester and amine salt forms of 2,4-D have similar soil dissipation rates because they areconverted rapidly to the same anionic form.⁴⁵
• 2,4-D has a low binding affinity in mineral soils and sediment, and in those conditions is considered intermediately tohighly mobile.³ In sandy loam, sand, silty clay loam, and loam soil, K_oc values of 70, 76, 59, and 117 mL/g, respectively, wereobtained,³ indicating low binding affinity in these soil types. Although 2,4-D is highly mobile, rapid mineralization ratesmay reduce the potential of 2,4-D to affect groundwater.⁴⁶ Microbes may play a major role in degradation.²
• Break-down products of 2,4-D detected in laboratory experiments included 1,2,4-benzenetriol, 2,4-dichlorophenol (2,4-DCP), 2,4-dichloroanisole (2,4-DCA), 4-chlorphenol, chlorohydroquinone (CHQ), volatile organics, bound residues, and carbondioxide. These degradates are expected to be of low occurrence in the environment, of low toxicity, or both.³

Water

• The half-life of 2,4-D in aerobic aquatic environments was estimated to be 15 days and in anaerobic aquatic laboratorystudies, 41-333 days.³ A granular formulation of the BEE form degraded rapidly in the water column in alkaline conditionsbut was present in sediments for 186 days.³
• The ethyl hexyl form is rapidly hydrolyzed in water to 2,4-D acid, with a degradation half-life (DT₅₀) of less than one day.¹Ester forms of 2,4-D hydrolyze at rates that are pH dependent; the hydrolysis half-life of the butoxy ester increased from 9hours at pH 8 to more than one year in more acidic conditions with a pH of 5.38 The acid form of 2,4-D is very resistant toabiotic hydrolysis.³
• 2,4-D has been detected in streams and shallow groundwater at low concentrations, in both rural and urban areas.^3,47,48

Air

• Volatility for most forms of 2,4-D is low (see the table on 2,4-D and associated forms). However, the vapor pressure of some ester forms rangefrom 1.1 x 10^-3 to 2.3 x 10^-3 mmHg,² indicating that these forms readily volatilize. The Henry's Law Constant for 2,4-D acid is3.5 x 10^-4 at pH 7,⁴⁹ indicating low potential for movement from water to air.
• No data were found regarding the degradation of 2,4-D in the atmosphere.

Plants

• The ester forms of 2,4-D penetrate foliage, whereas plant roots absorb the salt forms.¹² Ester forms are converted to theacid within the plant, then accumulate in cells due to passive diffusion down the concentration gradient.¹² Active transportwithin the plant may also occur.¹² Accumulation occurs primarily at the meristem tissue of roots and shoots.¹
• Forest dissipation studies indicated that the ethyl hexyl ester form of 2,4-D degraded slowly on foliage and in leaf litter.³Residues of an ester form of 2,4-D were detected in samples of dead birch leaves for up to three years post-application.⁵⁰

Indoor

• No data were available on indoor persistence.

Food Residue

• 2,4-D was not included in the list of pesticides detectable in regulatory monitoring.⁵¹

  Maximum Contaminant Level (MCL): The MCL is the highestlevel of contaminant that is legally allowed in drinking water.The MCL is enforceable. The MCL is typically measured inmilligrams (mg) of contaminant per liter (L) of water.

  U.S. Environmental Protection Agency, National Primary Drinking Water Regulations. https://www.epa.gov/ground-water-and-drinking-water/national-primary-drinking-water-regulations#one

• Traces of 2,4-D were detected in 49.3% of finished drinkingwater samples and 53.7% of untreated water samples (365 and367 samples taken, respectively), with detections between 1.1and 2416.0 parts per trillion (ppt). These concentrations arewell below the maximum contaminant level (MCL) of 70,000ppt set by the U.S. EPA for finished drinking water.⁵² In bottledwater, only 2 of 367 samples contained 2,4-D, with residues of3.2 and 4.2 ppt.⁵² See the text box on Maximum Contaminant Level (MCL).

Ecotoxicity Studies:

Birds

• LD₅₀ values range from 472 mg/kg for acute oral exposure in pheasants, to 668 mg/kg in pigeons and Japanese quail, togreater than 1000 mg/kg in wild ducks.¹ The acute oral LD₅₀ for the dimethyl amine salt form of the compound was 500mg/kg for bobwhite quail, and the acute oral LD₅₀ for the ethyl hexyl form was 663 mg/kg in mallard ducks. The acute oralLD₅₀ for wild ducks was in excess of 2025 mg/kg for the sodium salt form of 2,4-D.¹ Overall, 2,4-D is moderately toxic topractically non-toxic to birds. There are no pronounced differences in toxicity based on the form of 2,4-D.³
• Five-day studies estimated LC₅₀ values for bobwhite quail and mallard ducks at greater than 5620 ppm.¹ Chronic studieshave also demonstrated low toxicity, with no effects observed below very high exposure levels such as concentrations indrinking water greater than the solubility of the chemical.² Under field conditions, eggs of ground-nesting birds could beexposed, but eggshell permeability to 2,4-D is low and treating eggshells with high concentrations of 2,4-D did not reducehatchability or cause chick abnormalities.²

Fish and Aquatic Life

• Toxicity to fish and aquatic invertebrates varies widely depending on chemical form, with esters being the most toxic.^1,2Acid and amine salt LC₅₀s range from greater than 80 to 2244 mg acid equivalents per liter (mg ae/L) whereas the estersrange from less than 1.0 to 14.5 mg acid equivalents per liter.³ The greater toxicity generally of the esters in fish is likely dueto the greater absorption rates of the esters through the gills, where they are hydrolyzed to the acid form.² The acute LC₅₀of the dimethyl amine salt form to rainbow trout was 100 mg/L,¹ which is considered slightly toxic.
• The acute LC₅₀ of the ethyl hexyl form to rainbow trout was greater than its solubility in water.¹ The LD₅₀ value for the isoctylform (CASRN 25168-26-7) in cutthroat trout was 0.5-1.2 mg/L,¹ or moderately to highly toxic. Adult fathead minnowsexhibited toxic effects at chronic exposures of the butoxyl ethanol ester form that were 1/10 to 1/45 of the 96-hour LC₅₀concentrations.² Early life stages of fish are more susceptible compared with adult fish or eggs.²
• Daphnia exposed to the acid form for 21 days exhibited an LC₅₀ of 235 mg/L when exposed to 2,4-D acid for 21 days, andan LC₅₀ of 5.2 mg/L when exposed to the ethyl hexyl form for 48 hours.¹ Therefore, the acid form is practically non-toxic toDaphnia but the ethyl hexyl form is moderately toxic. As with fish, esters are more toxic than acid or amine salt forms tofreshwater aquatic invertebrates, with LC₅₀ values ranging from 25 to 643 mg ae/L for the acid and amine salt forms but 2.2to 11.8 mg ae/L for esters.³ The relative toxicities for acids and salts are slightly toxic to practically non-toxic, whereas theesters are moderately to slightly toxic.
• Marine invertebrate sensitivities are similar to aquatic invertebrates, with LC₅₀ values of 50-830 mg ae/L for acid and saltforms and >0.092 to >66 mg ae/L for ester forms.³ The corresponding relative toxicity values are slightly toxic to practicallynon-toxic for the salts and acid but highly toxic to practically non-toxic for the ester forms.
• Researchers have estimated a No Observed Effect Concentration (NOEC) of 16.1 mg ae/L for the DEA ester and 79.0 mgae/L for the acid form based on survival and reproduction for DEA and number of young produced for the acid form. Thefreshwater aquatic invertebrate NOEC for the BEE ester was estimated at 0.2 mg ae/L based on survival and reproduction.³
• 2,4-D is marketed for controlling aquatic plants. Therefore, thelethal concentrations are reported as effective concentrationsfor killing half the target population (EC₅₀). Researchers estimatedan EC₅₀ of 0.58 mg/L for duckweed (Lemna gibba). A varietyof algal species exhibited LC₅₀ values ranging between 0.23 andgreater than 30 mg/L for the ethyl hexyl form.¹ The EC₅₀ for thedimethyl amine salt form against Selenastrum capricornutumwas estimated at 51.2 mg/L.¹ No effects were recorded for 19genera of algae exposed to 2,4-D at concentrations of up to 222mg/L.² However, the ester forms were toxic to some algae atmuch lower concentrations.² See the text box on EC₅₀.

  EC₅₀: The median effective concentration (EC₅₀) may bereported for sublethal or ambiguously lethal effects. Thismeasure is used in tests involving species such as aquaticinvertebrates where death may be difficult to determine.This term is also used if sublethal events are beingmonitored.

  Newman, M.C.; Unger, M.A. Fundamentals of Ecotoxicology; CRC Press, LLC.:Boca Raton, FL, 2003; p 178.

• A mesocosm study indicated that an unspecified form of 2,4-D applied at 0.117 mL/m² had no negative effects onspecies richness, biomass, or survival on algae and 25 species of aquatic animals, including frog larvae, salamanders,snails, and a range of other invertebrates.⁵³ Ninety-six-hour LC₅₀ concentrations for several species of amphibian larvaeexceeded 100 mg/L for the amine salt forms.² 2,4-D acid, 2,4-D EHE, and 2,4-D DMA are considered practically non-toxic toamphibian larvae based on tests with Rana pipiens.³
• Bioavailability and uptake of 2,4-D by organisms are strongly influenced by pH, temperature, and other environmental factors.² The sensitivity of aquatic invertebrates to 2,4-D increases with temperature; concentrations below those associatedwith short-term toxic effects impaired reproduction when ambient temperature was elevated.² Although some aquaticinvertebrates appear to sense and avoid 2,4-D in the water, others do not, even when exposed to lethal concentrations.²Fish appear to avoid 2,4-D in a dose-dependent manner until the onset of toxic effects.² Toxicity of 2,4-D was increasedwhen fish were simultaneously exposed to 2,4-D and carbaryl or picloram.²

Terrestrial Invertebrates

• LC₅₀ values for 24-hour exposures in honey bees (Apis mellifera) were estimated to be 104 and 115 μg per bee. Researchers estimated theLD₅₀ at greater than 10 μg/bee, so 2,4-D is considered practically non-toxic.³ Effects on bee longevity varied according todose and 2,4-D form.²
• 2,4-D is not considered hazardous to beneficial insects due to its low insecticidal activity and an adequate safety marginwhen products containing 2,4-D are used at recommended levels.^2,3
• Carabid beetles (Carabidae) exposed to sand dosed with 1 g/m² exhibited greater than 50% mortality after 4 days.²
• The calculated 48-hour LC₅₀ concentration for earthworms (Lumbricus rubellus) exposed to filter paper treated with 2,4-D was 61.6 μg/cm.²²
• Effects of 2,4-D on soil microorganisms were species-dependent.²

Regulatory Guidelines:

• The reference dose (RfD) for 2,4-D is 0.01 mg/kg/day.⁵⁴ See the text box on Reference Dose (RfD).

  Reference Dose (RfD): The RfD is an estimate of the quantity ofchemical that a person could be exposed to every day for the restof their life with no appreciable risk of adverse health effects. Thereference dose is typically measured in milligrams (mg) of chemicalper kilogram (kg) of body weight per day.

  U.S. Environmental Protection Agency, Integrated Risk Information System, IRIS Glossary, 2009. https://www.epa.gov/iris/iris-glossary#r

• The U.S. EPA has classified 2,4-D as "Group D - not classifiablewith regard to human carcinogenicity" in 2004.³IARC had not assigned 2,4-D a cancer rating as of December2007. However, the chlorophenoxy herbicidesas a group were classified in Group 2B, meaning thatthey are considered to be possibly carcinogenic to humans,by IARC in 1987.²⁹ See the text box on Cancer.
• The threshold limit value, or TLV, for 2,4-D is 10 mg/m³ for an 8-hour time weighted average exposure.⁵⁵ This limit is basedon results of animal feeding experiments.⁴³ This same dose was selected by the Occupational Safety and Health Administration(OSHA) for the permissible exposure limit (PEL) for an 8-hour time weighted average exposure and by the NationalInstitute for Occupational Safety and Health (NIOSH) for the recommended exposure limit (REL) for a 10-hour workday anda 40-hour workweek.⁴³
• The MCL for 2,4-D in drinking water is 0.07 mg/L.⁵⁶ See the text box on Maximum Contaminant Level (MCL).

Date Reviewed: November 2008

Please cite as: Gervais, J.; Luukinen, B.; Buhl, K.; Stone, D. 2008. 2,4-D Technical Fact Sheet; National PesticideInformation Center, Oregon State University Extension Services. http://npic.orst.edu/factsheets/archive/2,4-DTech.html.