NA 2,4Dichlorophenoxyacetic acid [factsheet]

2,4-DICHLOROPHENOXYACETIC ACID

(2,4-D)

(including salts and esters)

Please Note: The main sources 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, and EPA's 2,4-Dichlorophenoxyacetic Acid Health Advisory. 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literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational 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 of acute (short-term) 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 animals, such as the LD₅₀ tests in 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 (long-term) 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 an RfC for 2,4-D. (5)

* The RfD for 2,4-D is 0.01 mg/kg/d based on hematologic, hepatic and renal toxicity in rats. (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)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has evaluated 2,4-D for chronic toxicity and has given it a composite score of 18 (scores range from 1 to 100, with 100 being the most toxic). These scores are nonlinear and are the product of two ratings: a rating based on the minimal-effect-dose and a rating based on the type of effect. (6)

Reproductive/Developmental Effects:

* No information is available on the reproductive or developmental effects of 2,4-D in humans.

* 2,4-D appears to be embryotoxic but only weakly teratogenic (causes birth defects) in animals. 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 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. (1,3,7,8)

* Limited animal data are available on the carcinogenicity of 2,4-D. 2,4-D has been tested in rats and mice by oral administration resulting in an increased tumor incidence. (7,8)

* A more recent study of rats exposed to 2,4-D by ingestion showed an increased incidence of lymphosarcomas in both sexes, and cancer of the mammary gland in females. (1)

* EPA has classified 2,4-D as a Group D, not classifiable as to human carcinogenicity, based on a lack of data concerning carcinogenicity in humans and animals. (3)

* However, IARC has recently classified 2,4-D as a Group 2B, i.e., the agent is possibly carcinogenic to humans. (1)

Physical Properties

* The chemical formula for 2,4-D is C₈H₆Cl₂O₃, and its molecular weight is 221.04 g/mol. (9)

* 2,4-D occurs as a white crystalline powder that is almost insoluble in water. (1,3,9)

* 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)

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)

Health Data from Inhalation Exposure

Concentration (mg/m³/d)	Health numbers^a	Regulatory, advisory numbers^b	Reference
1,000.0
_ _ _ _ 100.0
_ _ _ _ 10.0		* ACGIH TLV, NIOSH REL, MSHA standard, OSHA PEL (10 mg/m³)	4
_ _ _ _ 1.0
_ _ _ _ 0.1

ACGIH TLVCAmerican 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.

MSHACMine Safety and Health Administration.

NIOSH RELCNational Institute of Occupational Safety and Health recommended exposure limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PELCOccupational 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.

^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.

References

1. 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.

2. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes Publications, Park Ridge, NJ. 1985.

3. U.S. Environmental Protection Agency. 2,4-Dichlorophenoxyacetic Acid Health Advisory. Office of Drinking Water, Washington, DC. 1987.

4. 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.

5. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on 2,4-Dichlorophenoxyacetic Acid. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

6. U.S. Environmental Protection Agency. Technical Background Document to Support Rulemaking Pursuant to the Clean Air ActCSection 112(g). Ranking of Pollutants with Respect to Hazard to Human Health. EPAB450/3-92-010. Emissions Standards Division, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.

7. 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.

8. International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Chemicals, Industrial Processess and Industries Associated with Cancer in Humans. IARC Monographs, Volumes 1 to 29. Supplement 4. World Health Organization, Lyon. 1982.

9. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

10. U.S. Environmental Protection Agency. Pesticide Fact Handbook. Noyes Data Corporation, Park Ridge, NJ. 1988.