2,4-D (2,4-Dichlorophenoxyacetic Acid)

(including salts and esters)

94-75-7

Hazard Summary-Created in April 1992; Revised in January 2000

2,4-D is a herbicide used on a number of crops. At high concentrations it affects the central nervous system (CNS) in humans, with symptoms including stiffness of arms and legs, incoordination, lethargy, anorexia, stupor, and coma. 2,4-D is also an irritant to the gastrointestinal tract and skin in humans. Chronic (long-term) oral exposure to 2,4-D results in effects on the blood, liver, and kidneys in animals. Several human studies have suggested an association between exposure to 2,4-D (and other herbicides) and an increased incidence of tumor formation. However, it is not clear whether this represents a true association, and, if so, whether it is specifically related to 2,4-D. Some studies have reported increased incidences of tumors in orally exposed animals. EPA has not classified 2,4-D as to its human carcinogenicity.

Please Note: The main source of information for this fact sheet are EPA's Integrated Risk Information System (IRIS), which contains information on oral chronic toxicity of 2,4-D and the RfD. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Uses

2,4-D is used as a systemic herbicide to control broadleaf weeds in wheat, corn, rangeland/pastureland, sorghum, and barley. Over 1500 pesticide products contain 2,4-D as an active ingredient. (1,2,3,10)

Sources and Potential Exposure

Individuals are most likely to be exposed to 2,4-D by inhalation or dermal contact during its manufacture, formulation, or application. (1,2)
2,4-D has been detected in a small number of drinking water supplies at low concentrations; this contamination appears to be the result of agricultural runoff. (1,3)
In the 1970s, 2,4-D was reported to occur in some foods; more recent surveys have failed to find detectable levels. (3)

Assessing Personal Exposure

No information was located concerning the measurement of personal exposure to 2,4-D.

Health Hazard Information

Acute Effects:

Neurotoxicity is the predominant effect from acute inhalation and oral exposure to 2,4-D, with symptoms including stiffness of arms and legs, incoordination, lethargy, anorexia, stupor, and coma in humans. 2,4-D is also an irritant to the gastrointestinal tract, causing nausea, vomiting, and diarrhea. (1,3)
Dermal contact with 2,4-D may result in a rash or dermatitis in humans. (1)
Tests involving acute exposure of rats, mice, rabbits, and hamsters, have demonstrated 2,4-D to have high acute toxicity from oral and dermal exposure. (4)

Chronic Effects (Noncancer):

Hematologic, hepatic, and renal toxicity have been demonstrated from chronic oral exposure to 2,4-D in animal studies. Specifically, a reduction in hemoglobin and red blood cells, decreased liver enzyme activity, and increased kidney weight have been observed. (1,5)
EPA has not established a Reference Concentration (RfC) for 2,4-D. (5)
The Reference Dose (RfD) for 2,4-D is 0.01 milligrams per kilogram body weight per day (mg/kg/d) based on effects on the blood, liver, and kidneys in rats. The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups), that is likely to be without appreciable risk of deleterious noncancer effects during a lifetime. It is not a direct estimator of risk but rather a reference point to gauge the potential effects. At exposures increasingly greater than the RfD, the potential for adverse health effects increases. Lifetime exposure above the RfD does not imply that an adverse health effect would necessarily occur.(5)
EPA has medium confidence in the principal study on which the RfD was based because a fair number of animals of each sex were used, four doses were given, and a good number of parameters were measured; medium confidence in the database because several studies support both the observation of critical toxic effects and the levels at which they occur; and, consequently, medium confidence in the RfD. (5)

Reproductive/Developmental Effects:

No information is available on the reproductive or developmental effects of 2,4-D in humans.
Increased mortality and weight loss have been observed in the offspring of rats orally exposed to high levels of 2,4-D. Decreased fetal weights, increased fetal mortality, and skeletal malformations have been reported in the offspring of mice, rats, and hamsters exposed to 2,4-D orally. (1,3,7)

Cancer Risk:

Several human studies have suggested an association between exposure to 2,4-D (and other herbicides) and an increased incidence of tumor formation. However, it is not clear whether this represents a true association, and if so, whether it is specifically related to 2,4-D. (1,3,6,7)
Ingestion exposure of rats to 2,4-D resulted in an increased incidence of lymphosarcomas in both sexes, and cancer of the mammary gland in females. (1)
EPA has not classified 2,4-D for human carcinogenicity. (5)

Physical Properties

The chemical formula for 2,4-D is C₈H₆Cl₂O₃, and its molecular weight is 221.04 g/mol. (8)
2,4-D occurs as a white crystalline powder that is almost insoluble in water. (1,3,8)
2,4-D has a slight phenolic odor; the odor threshold has not been established. (2)
The log octanol/water partition coefficient (log K_ow) for 2,4-D is 2.81. (1)

Conversion Factors:
To convert concentrations in air (at 25°C) from ppm to mg/m³: mg/m³ = (ppm) × (molecular weight of the compound)/(24.45). For 2,4-dichlorophenoxyacetic acid: 1 ppm = 9.04 mg/m³.

Health Data from Inhalation Exposure

ACGIH TLV--American Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effects.
NIOSH IDLH--National Institute of Occupational Safety and Health's immediately dangerous to life or health limit; NIOSH recommended exposure limit to ensure that a worker can escape from an exposure condition that is likely to cause death or immediate or delayed permanent adverse health effects or prevent escape from the environment.
NIOSH REL--NIOSH's recommended exposure limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure and/or ceiling.
OSHA PEL--Occupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

The health and regulatory values cited in this factsheet were obtained in December 1999.
^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.
^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice. OSHA numbers are regulatory, whereas NIOSH and ACGIH numbers are advisory.

References

U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.
M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes Publications, Park Ridge, NJ. 1985.
U.S. Environmental Protection Agency. 2,4-Dichlorophenoxyacetic Acid Health Advisory. Office of Drinking Water, Washington, DC. 1987.
U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.
U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on 2,4-Dichlorophenoxyacetic Acid. National Center for Environmental Assessment, Office of Research and Development, Washington, DC. 1999.
International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man: Some Fumigants, the Herbicides 2,4-D and 2,4,5-T, Chlorinated Dibenzodioxins and Miscellaneous Industrial Chemicals. Volume 15. World Health Organization, Lyon. 1977.
International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Chemicals, Industrial Processes and Industries Associated with Cancer in Humans. IARC Monographs, Volumes 1 to 29. Supplement 4. World Health Organization, Lyon. 1982.
The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck and Co. Inc., Rahway, NJ. 1989.
U.S. Environmental Protection Agency. Pesticide Fact Handbook. Noyes Data Corporation, Park Ridge, NJ. 1988.
American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological Exposure Indices. Cincinnati, OH. 1999.
National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to Chemical Hazards. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.
Occupational Safety and Health Administration (OSHA). Occupational Safety and Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29 CFR 1910.1000. 1998.