United Statej Office of PertleWej and Toxic Sufactincn
Environmental Protection Office of Pettiade Programs (TS-766C)
Agency Washington, DC 20460
oEPA Pesticide
Fact Sheet
Name of Chemical: 2,4 - D
Reason for Issuance: update
Date Issued: March 1937
Fact Sheet Number:
94.1
1 . DESCRIPTION OF CHEMICAL
Generic Name: (2,4-Dichlorophenoxy) acetic acid
Common Name: 2,4-D (includes parent acid as well as
the 35 derivatives (esters and salts))
EPA Shaughnessy code: 030001
Chemical Abstracts Service (CAS) number: 94-75-7
Year of Initial Registration: 1948
Pesticide type: Herbicide, plant growth regulator
Chemical family: chlorinated phenoxys
2. USE PATTERNS AND FORMULATIONS
2,4-D is a systemic herbicide widely used to control
broadleaf weeds. There are approximately 1500 registered
products containing 2,4-D active ingredient. Over 60 million
pounds of 2,4-D active ingredients are annually applied
domestically with the majority used for control of broadleaf
weeds in wheat, field corn, grain sorghum, sugar cane, rice,
barLey, '"and range and pastureland.
USE PATTERNS
\
Agricultural; wheat, field corn, grain sorghum, sugar cane,
rice, barley, soybeans, orchard crops.
Aquatic Management; water hyacinth control; Tennessee Valley
Authority (TVA) Eurasian watermilfoil; lakes, ponds where treated
water is not used for domestic or irrigation purposes.
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Pasture and Rangeland brush control
Home and Garden : lawns, ornamental, turf, parks, recreation areas.
Forest Management : brush control, conifer release, tree injection.
TYPES AND METHODS OF APPLICATION : aerial and ground equipment,
knapsack sprayers, pressure andThose—end applicators, and lawn
spreaders.
TYPES OF FORMULATIONS : granular, amine and ester liquids, dust
aerosol spray (foam).
TOLERANCES :
Tolerances are established for residues of 2,4-D acid in a
variety of raw agricultural commodities, meat, milk, eggs, poultry,
fish, and shellfish. The tolerances include residues of 2,4-D
as a result of the application of the 2,4-D acid, as well as the
salts and esters. (These tolerances are listed in Attachment 1).
Food additive tolerances have been established for sugarcane,
molasses, milled fractions from barley, oats, rye, and wheat,
and potable water as a result of the use of 2,4—D in specific
aquatic management programs.
3. AGENCY REVIEW
The Agency initiated a review of the information available on
2,4-D in 1980 in order to address questions concerning potential
health effects associated with the use of 2,4—D. This review
was conducted to determine if 2,4—D should be reviewed under
the Special Review process or if another regulatory action was
appropriate. After a review of much of the existing toxicology
data supporting 2,4-D registrations, the EPA concluded that
the available information did not indicate that the continued
use of 2,4-D posed a significant health hazard when used in
accordance with label directions and precautions. The Agency
did conclude, however, that more information on 2,4—D toxicolo-
gical properties was necessary to better assess the potential
health hazards associated with the use of 2,4—D.
On August 29, 1980, after consulting with the Scientific
Advisory Panel (SAP), the Agency issued a data call-in letter
under authority of Section 3(c)(2)(B) of the Federal Insecticide,
Fungicide and Rodenticide Act (FIFRA) to registrants of 2,4-D.
The letter required submission of data on the following potential
health effects: acute toxicity (oral and dermal), oncogenicity
(tumor formation) in rat and mouse, reproduction, teratogenicity
(birth defects), neurotoxicity, and metabolism.
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Major registrants of technical 2,4—D products subject to
the data requirements have formed the “Industry Task Force on
2 1 4—D Research Data” (Task Force) to jointly produce the
required data.
The following data have been submitted by the Task Force
to support the 2,4—D registrations:
o Acute Oral and Dermal Toxicity Studies
(Rabbit, Rat) for all manufacturing use products
o Teratology Studies (Rat) for 2,4—D acid and
2,4—D Dichiorophenol
o Reproduction Study (Rat) for 2,4—D acid
o Pharmacokinetjc (Metabolism) Study (Rat, Mouse) for
2,4—D acid and isooctyl ester of 2,4—D
o Neurotoxicity Study (Rat) for 2,4—D acid
o Combined Chronic Toxicity and Oncogenicity Study
(Rat) for 2,4—D.
o Oncogenicity Study (Mouse) for 2,4—D acid
All required studies have been submitted; the results of
the major studies submitted are summarized below.
Teratology Study (Rat) 2,4—D acid
Fischer 344 female rats were administered doses of 2,4—D
acid (technical cirade) suspended in corn oil by gavage (oral
intubatjon) of 8, 25, or 75 mg/kg on days 6—15 of gestation
(35 rats/dose group). The results of the study were:
Maternal toxicity No Observed Effect Level (NOEL) = 75 mg/kg/day
Maternal toxicity Lowest Effect Level (LEL) = not found,
since NOEL was at the highest dose tested.
Fetotoxjc NOEL 25 mg/kg/day
Fetotoxjc LEL = 75 mg/kg/day (delayed ossification of bones)
The study does not indicate a teratogenic (birth defects)
effect up to 75 mg/kg/day.
Teratology Study (Rat ) 2 1 4—Dichloropheno]. (ester)
Fischer 344 female rats were gavaged on days 6—15 of gestation
with 0, 200, 375 or 750 mg/kg of 2,4—Dichioropheno]. suspended
in corn oil at 4 ml/kg. The results of the study were:
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Maternal toxicity LEL = 200 mg/kg
Fetotoxic NOEL = 375 rag/kg
Fetotoxic LEL = 750 mg/kg (delayed ossification of bones)
The test material was not teratogenic under the conditior s
of the study.
Reproduction Study (Rat) 2,4—D acid
Fischer 344 rats were administered 5, 20, or 80 mg/kg/day
of 2,4—D acid in the diet. The results indicate:
Maternal toxicity NOEL = 5 ma/kg/day
Maternal toxicity LEL = 20 mg/kg/day
Fetotoxic NOEL = 5 mg/kg/day
Fetotoxic LEL = 20 mg/kg/day
The results indicated that at the lowest dose tested of
5.0 mg/kg/day neither parent nor offspring were affected by the
administration of the chemical. However, at the next higher
dose tested (20 mg/kg/day) there was a decrease in maternal
body weight and reduced pup weiqht (weight of offspring).
There were no effects seen on fertility in male or female
rats.
Neurotoxicity (Rat) Dimethylanine salt of 2,4—D
Four groups of male and female Fischer CDF 344 rats (15 rats/
group) were used in a study to determine whether repeated dermal
exposure to 2,4—dimethylamine on the peripheral nervous system
of rats would result in pharmacological and/or toxicological
effects. The skin of the animals in the three treatment groups
was painted with a 12% 2,4—D amine solution for 2 hrs/day
5 days per week for 3 weeks. Control animals were treated
with tap water.
Derrnal exposure to 2,4—D resulted in two systemic effects:
treated rats weighed less than controls and the kidneys of
treated rats weiahed more than the controls. Even though the
rats had clear systemic effects of exposure to 2,4—D there
were no treatment—related changes in the function or structure
of the nervous system.
Oncogenicity (Rat)
Male and female rats (strain—CDF(F344)/CRL—BR)) were
administered doses of 1, 5, 15, and 45 mg/kg/day of 2,4—D
acid in the diet. The results of the study indicate that the
administration of 2,4—D appears to produce increased numbers
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of astrocytomas in brains of male rats at 45 mg/kg/day and
is suggestive of a carcinogenic effect. The Agency is currently
reviewing the study and will make a final determination on the
significance of the study in the Spring of 1987.
Oncogenicity (Mouse)
The mouse oncogenicity data were submitted in January 1987
and are under review by the Agency. The review is scheduled for
completion in the spring of 1987..
Epidemiologic Studies
Approximately 30 epidemiologic studies have been published
regarding the carcinogenic risk of herbicides, especially the
chlorinated phenoxy herbicides which include 2,4—D. The Agency
is undertaking a comprehensive review of these epidemiologic
studies to evaluate the weight of evidence pertaining to the
carcinogenic potential of 2,4—D.
4. SUMMARY OF MAJOR DATA GAPS
Environmental fate, residue chemistry, product chemistry,
and ecological effects data gaps are to be identified as part of
the Registration Standard development which is due to be issued
in early 1988.
5. REVIEW OF DATA
The Agency is reviewing the laboratory oncogenicity data
and the epidemiologic studies. The Agency will classify 2,4—D
under the Guidelines for Carcinogen Risk Assessment in the
Spring of 1987. That classification will be presented to the
Office of Pesticide Programs’ Science Advisory Panel (SAP) in
a public forum the Summer of 1987. After SAP review of the
Agency’s classification; the Agency will publish its
determination regarding 2,4—D oncogenicity in the Federal
Register.
6. CONTACT PERSON AT EPA
Douglas McKinney
Registration Division
U.S. Environmental Protection Agency
401 M Street, SW.
Washington, D.C. 20460
703—557—5488
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