E X T O X N E T
Extension Toxicology Network
A Pesticide Information Project of Cooperative Extension Offices of
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University of California at Davis. Major support and funding was provided
by the USDA/Extension Service/National Agricultural Pesticide Impact
Assessment Program.
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Pesticide
Information
Profile
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2,4-D
Publication Date: 9/93
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TRADE OR OTHER NAMES
2,4-D is used in many commercial products. A few commercial names
for products containing 2,4-D include Weedtrine-II, Aqua-Kleen, Barrage,
Plantgard, Lawn-Keep, Planotox and Malerbane.
INTRODUCTION
2,4-D, a chlorinated phenoxy compound, functions as a systemic
herbicide and is used to control many types of broadleaf weeds. There
are many forms or derivatives (esters, amines, salts) of 2,4-D and these
vary in solubility and volatility. Unless otherwise specified, this
document will refer to the acid form of 2,4-D. This compound is used in
cultivated agriculture and in pasture and rangeland applications, forest
management, home and garden situations and for the control of aquatic
vegetation.
2,4-D was a major component (about 50%) of the product Agent Orange
used extensively throughout Vietnam. However most of the problems
associated with the use of Agent Orange were associated with a
contaminant (dioxin) in the 2,4,5-T component of the defoliant. The
association of 2,4-D with Agent Orange has prompted a vast amount of
study on the herbicide.
TOXICOLOGICAL EFFECTS
ACUTE TOXICITY
While the LD50 of 2,4-D suggests that it is only moderately toxic,
the product carries the DANGER signal word on the label indicating that
it is highly toxic. This is because 2,4-D has produced serious eye and
skin irritation among agricultural workers (15,16).
The oral LD50 of 2,4-D in the rat ranges from 375 to 666 mg/kg; 370
mg/kg in the mouse; and less than 320 to 1,000 mg/kg in the guinea pig.
The rat and rabbit have dermal LD50 values of 1,500 mg/kg and 1,400
mg/kg, respectively. In humans, prolonged breathing of 2,4-D causes
coughing, burning, dizziness, and temporary loss of muscle coordination.
Symptoms of poisoning can be fatigue and weakness with perhaps
nausea. On rare occasions there can be inflammation of the nerve
endings with muscular effects following high levels of exposure (6).
Symptoms vary with the different commercial products because of the
specific amounts and types of additives such as surfactants and
solvents.
CHRONIC TOXICITY
Rats given moderate amounts (50 mg/kg) of 2,4-D in the diet for two
years had no adverse effects. Some dogs fed lower amounts of the
compound in their food for two years died, probably because dogs do not
excrete organic acids efficiently. A human given a total of 16.3 grams
in 32 days as "desperation therapy" lapsed into a stupor, showed signs
of incoordination, weak reflexes, and urinary incontinence.
Reproductive Effects
Administration of drinking water dosed with moderate levels of 2,4-
D (about 50 mg/kg) to pregnant rats did not result in any adverse
effects on birth weights, or litter size. Rats fed higher levels (188
mg/kg) had fetuses with abdominal cavity bleeding and increased
mortality. DNA synthesis in the testes was significantly inhibited when
mice were fed large amounts (200 mg/kg) of 2,4-D (8). While there is
some conflicting evidence about the reproductive effects of the compound
in animals, most of the evidence suggests that 2,4-D causes reproductive
effects at moderate doses in animals. This indicates that humans may be
at risk with 2,4-D exposure though no direct evidence of reproductive
problems associated with 2,4-D exposure exists.
Teratogenic Effects
2,4-D has a very limited ability to cause birth defects. However,
rats fed 150 mg/kg on days 6-15 of pregnancy had an increase in skeletal
abnormalities such as delayed bone development and wavy ribs (10) which
are a function of general toxicity. The same conclusions may be drawn
for 2,4-D's potential to cause teratogenic effects in humans as was
noted above.
Mutagenic Effects
2,4-D has been very extensively tested for mutagenicity and found
to be non-mutagenic in most systems. However, significant increases of
damage occurred in chromosomes in cultured human cells at low exposure
levels (17). 2,4-D did not damage DNA in human lung cells. The
evidence is too equivocal to draw any conclusions.
Carcinogenic Effects
Low doses fed to rats for two years caused an increase in malignant
tumors (10). There was some question about whether the tumors were
associated with specific organs or were non-specific. Female mice given
a single injection of 2,4-D developed cancer (reticulum-cell sarcomas)
(10).
The studies of 2,4-D carcinogenicity mentioned above are considered
to be inadequate by IARC (International Agency for Research on Cancer).
New studies, completed in 1986, show a low incidence of brain tumors at
moderate exposure levels (45 mg/kg/day) over a lifetime.
In humans, a variety of studies give conflicting results. Several
studies in Sweden and the United States (Kansas (1) and Nebraska (21)),
suggest an association of 2,4-D exposure with cancer. An increased
occurrence of non-Hodgkin's lymphoma was found among a Kansas and
Nebraska farm population associated with the spraying of 2,4-D. Other
studies done in New Zealand, Washington, New York, Australia, and on
Vietnam veterans from the United States were all negative. There remains
considerable controversy about the methods used in the various studies
and thus with the results of the various studies (20). Investigations
are continuing.
Organ Toxicity
Most symptoms disappear within a few days but there is a report of
liver dysfunction from long term exposure (6).
Fate in Humans and Animals
The absorption of the herbicide is almost complete in mammals after
ingestion and nearly all of a dose is excreted in the urine. The
compound is readily absorbed through the skin and lungs also. When five
men were given 5 mg/kg, they excreted most of the dose (about 82%) as
unchanged 2,4-D.
Only traces of the compound have been found in the milk of
lactating animals for six days following exposure. The half-life is
between 10 and 20 hours in living organisms. There is little evidence
to suggest that the compound accumulates to any significant level in
mammals or in other organisms (18). Peak concentrations of 2,4-D were
found in the blood, liver, kidney, lungs and spleen with lower levels in
muscle and brain between six and eight hours after small doses (1
mg/kg) were given to rats. After 24 hours there were no detectable
tissue residues.
2,4-D passes through the placenta in pigs and rats. In rats, about
20% was detected in the uterus, placenta, fetus, and amniotic fluid
(12). Chickens given moderate amounts of 2,4-D in drinking water from
birth to maturity had very low levels of the compound in egg yolks and
only a trace in the egg whites.
ECOLOGICAL EFFECTS
2,4-D is slightly toxic to wildfowl. Mallards, pheasants, quail,
and pigeons had LD50 levels of >1000, 472, 668, and 668 mg/kg,
respectively.
Some formulations of 2,4-D are highly toxic to fish while others
are less so. For example the LC50 ranges between 1.0 mg/l to 100 mg/l
in cutthroat trout, depending on the formulation used. Channel catfish
had less than 10% mortality at 10 mg/l in 48 hours. Green sunfish when
exposed to 110 mg/l for 41 hours showed no effect on swimming response.
Limited studies indicate a half-life of less than 2 days in fish and
oysters when exposure is discontinued (11).
Brood production was severely impaired when honeybees were fed
moderate doses, but, at lower levels of exposure they lived
significantly longer than the controls. The honeybee LD50 is 11.5
micrograms/bee.
Concentrations of 10 mg/l for 85 days did not adversely affect the
survival of adult dungeness crabs. The early immature stages had an
LC50 of greater than 10 mg/l in 96 hours indicating that the compound is
only slightly toxic to these organisms. Brown shrimp had a small
increase in mortality at 2 mg/l over a 48 hour exposure period.
ENVIRONMENTAL FATE
2,4-D applied at 1.16 lb/acre to bluegrass turf in a laboratory
experiment had a half-life of ten days. Other half-life figures for the
herbicide in soil are seven days (15-25 degree C with 65% moisture) and
ten days in non-sterile soil and 1.5 to 16 days in other studies. Soil
microbes are primarily responsible for its disappearance in soil.
Studies in Alaska and Canada failed to detect leaching in 22 weeks or
from spring to fall (10), but 2,4-D has been included on the EPA list
of compounds that are likely to leach from soil.
In aquatic environments microorganisms readily degrade 2,4-D and
breakdown by sunlight is not a major reason for loss. Rates of
breakdown increase with increased nutrients, sediment load and dissolved
organic carbon. Under oxygenated conditions the half-life can be short,
in the order of one week to several weeks.
2,4-D interferes with normal plant growth processes. Uptake of the
compound is through leaves, stems and roots; however, it is generally
nonpersistent. In one study when 2,4-D was applied to grass, there were
80 ppm at day zero, 45 ppm at 14 days, and 6 ppm at 56 days. Breakdown
in plants is by a variety of biological and chemical pathways (11).
Despite its short half-life in soil and in aquatic environments,
the compound has been detected in groundwater supplies in at least five
States and in Canada (18). It has also been detected in surface waters
throughout the United States at very low concentrations.
DIOXIN CONTAMINATION
Although recently manufactured 2,4-D technical acids have
consistently been free of dioxin contamination, the amine and ester
products may have measurable levels of some forms of dioxin. According
to a study of 2,4-D manufactured in Canada (9), of 26 amine samples
tested, 8 were positive. The levels ranged from 5 ppb to nearly 500
ppb. Several different forms of dioxin were present in the different
products. All but one of 21 ester samples were positive.
Since an earlier study had reported finding hexachlorodioxin in
2,4-D the samples were analyzed for mono- to octachlorodioxin but no
other isomers were found above the detection limit of 10 ppb. A
subsequent study of 2,4-D manufactured in the United States found very
little dioxin contamination. Measurable amounts of one form of the
compound (2,7 DCDD) were found in 3 of 30 samples, with traces of other
isomers. The amounts found do not have biological significance.
Exposure Guidelines:
| NOEL (rats): | 1 mg/kg |
| ADI: | 0.3 mg/kg (WHO) |
| MCL: | 0.07 mg/l |
| HA: | 70 ug/l (lifetime) |
| TLV-TWA: | 10 mg/m3 |
| TLV STEL: | 20 mg/m3 |
| Dangerous Exposure: | 500 mg/m3 (OSHA/NIOSH) |
| RfD: | 0.01 mg/kg/day |
| LEL: | 5 mg/kg/day (rat) |
Physical Properties:
| CAS #: | 94-75-7 |
| Chemical Name: | (2,4-dichlorophenoxy) acetic acid |
| Chemical class/use: | phenoxy herbicide |
| Solubility in water: | 890 mg/l |
| Solubility in other solvents: | ethanol and acetone, 9.5 g/100 g;
benzene, 1.07 g/100g |
| Melting Point: | 138 degrees C |
| Vapor Pressure: | 8 x 10-6 mm Hg |
| Partition Coefficient: | 2.81 (octanol/water) |
BASIC MANUFACTURER
Rhone-Poulenc, Inc.
PO Box 12014
2 T.W. Alexander Dr.
Research Triangle Park, NC 27709
Telephone: 919-549-2000
Emergency: 800-334-7577
Review by Basic Manufacturer:
Comments solicited: October, 1992
Comments received:
REFERENCES
Hoar, S.K., A. Blair, F.F. Holmes, C.D. Boysen, R.J. Robel, R.
Hoover, J.F. Fraumeni, Jr. (1986). Agricultural Herbicide Use and Risk
of Lymphoma and Soft-Tissue Sarcoma, JAMA 256:9:1141-1147.
Newton, Michael and Frank N. Dost, (1984). Biological and Physical
Effects of Forest Vegetation Management. Washington Dept of Natural
Resources, Olympia, WA.
Shepard, Thomas H. (1986). Catalog of Teratogenic Agents. The
John Hopkins University Press, Baltimore, MD.
U. S. Environmental Protection Agency (1986-1988). Pesticide Fact
Sheet, Office of Pesticides and Toxic Substances, Office of Pesticide
Programs (TS-766C)
Wagner, Sheldon L. (1980). Clinical Toxicology of Agricultural
Chemicals. Environmental Health Sciences Center, Oregon State Univ.,
Corvallis, OR.
Gosselin, R.E., R.P. Smith, H.C. Hodge (1984). Clinical Toxicology
of Commercial Products, Williams and Wilkins, Baltimore, MD.
Cochrane, W.P., J. Singh, W. Miles, and B. Wakeford (1981).
Determination of Chlorinated Dibenzo-p-Dioxin Contaminants in 2,4-D
Products by Gas Chromatography - Mass Spectrometric Techniques, J of
Chromatography 217:289-299.
National Library of Medicine (1992). Hazardous Substances
Databank. TOXNET, Medlars Management Section, Bethesda, MD.
U. S. Environmental Protection Agency (1987). Health Advisory,
Office of Drinking Water.
Forest Service, (1984). Pesticide Background Statements, Vol. I
Herbicides. United States Department of Agriculture, Agriculture
Handbook No. 633.
National Research Council Canada (1978). Phenoxy Herbicides -
Their Effects on Environmental Quality with Accompanying Scientific
Criteria for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD). Subcommittee on
Pesticides and Related Compounds, NRC Associate Committee on Scientific
Criteria for Environmental Quality, Ottawa, Canada.
Food and Drug Administration (1986). The FDA Surveillance Index.
Bureau of Foods, Dept of Commerce, National Technical Information
Service, Springfield, VA.
Occupational Health Services, Inc. (1988). Hazardline, New York,
NY.
Canadian Centre for Toxicology (1987). Expert Panel Report on
Carcinogenicity of 2,4-D, Ontario Pesticide Advisory Committee of the
Ontario Ministry of the Environment, Toronto, Ontario, Canada.
The Agrochemicals Handbook. 1991. Royal Society of Chemistry.
Cambridge, England.
The Farm Chemicals Handbook. 1992. Meister Publishing Company.
Willoughby, Ohio.
Schlop, R.N., M.H. Hardy, and M.T. Goldberg. 1990. Comparison of
the activity of topically applied pesticides and the herbicide 2,4-D in
two short-term in vivo assays of genotoxicity in the mouse Fundamentals
of Applied Toxicology. 15:666-675
Howard, Philip H. Handbook of Environmental Fate and Exposure
Data for Organic Chemicals. Lewis Publishers Chelsea, Michigan.
Stevens, James T. and Darrell D. Sumner. 1991. Herbicides. in
Handbook of Pesticide Toxicology, Volume3, Classes of Pesticides.
Wayland J. Hayes and Edward R. LAws editors. Academic Press. New York.
The Federal Register. June 14, 1990. Volume 55 number 115 p.
24116. EPA Proposed Rules.
Zahm, S.H. Weisenburger, D.D., Babbitt, P.A. et.al. 1990. A
Case-control Study of Non-Hodgkin's Lymphoma and the Herbicide 2,4-
dichlorophenoxyacetic acid (2,4-D) in Eastern Nebraska. Epidemeology
1:349-356.
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criticism of unnamed products implied. Most of this information is historical
in nature and may no longer be applicable.
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