2,4-Dichlorophenoxyacetic acid (2,4-D) (CASRN 94-75-7)
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0150
2,4-Dichlorophenoxyacetic acid (2,4-D);
CASRN 94-75-7
Health assessment information on a chemical substance is included in IRIS
only after a comprehensive review of chronic toxicity data by U.S. EPA
health scientists from several Program Offices and the Office of Research
and Development. The summaries presented in Sections I and II represent
a consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR 2,4-Dichlorophenoxyacetic acid (2,4-D)
File First On-Line 03/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 05/05/1988 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — 2,4-Dichlorophenoxyacetic acid (2,4-D)
CASRN — 94-75-7
Last Revised — 05/05/1988
The oral Reference Dose (RfD) is based on the assumption that thresholds
exist for certain toxic effects such as cellular necrosis. It is expressed
in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily exposure to the human
population (including sensitive subgroups) that is likely to be without
an appreciable risk of deleterious effects during a lifetime. Please refer
to the Background Document for an elaboration of these concepts. RfDs
can also be derived for the noncarcinogenic health effects of substances
that are also carcinogens. Therefore, it is essential to refer to other
sources of information concerning the carcinogenicity of this substance.
If the U.S. EPA has evaluated this substance for potential human carcinogenicity,
a summary of that evaluation will be contained in Section II of this file.
NOTE: The Oral RfD for 2,4-D may change in the near future pending the
outcome of a further review now being conducted by the Oral RfD Workgroup.
__I.A.1. Oral RfD Summary
Critical Effect |
Experimental Doses* |
UF
|
MF
|
RfD
|
---|---|---|---|---|
Hematologic, hepatic 90-Day Rat Oral Dow Chemical Co., |
NOAEL: 1.0 mg/kg/day LOAEL: 5.0 mg/kg/day |
100
|
1
|
1E-2
mg/kg/day |
*Conversion Factors: none
__I.A.2. Principal and Supporting Studies (Oral RfD)
Dow Chemical Co. 1983. Acc. No. 251473. Available from EPA. Write to FOI,
EPA, Washington, DC 20460.
Hematologic, hepatic, and renal toxicity were demonstrated in a study in
Fischer rats (strain 344) during subchronic feeding performed at the Hazleton
Laboratories (1983). 2,4-D (97.5% pure) was added to the diet chow and fed to
the rats for 91 days at doses calculated to be 0.0 (controls), 1.0, 5.0, 15.0,
or 45.0 mg/kg/day. In each of the five groups there were 20 animals/sex and
40 animals/treatment group, for a total of 200 animals. Criteria examined to
determine toxicity were survival, daily examination for clinical
symptomatology, weekly change in body weights, growth rates, food intake,
ophthalmologic changes, changes in organ weights, and clinical, gross and
histopathologic alterations. The results of the study demonstrated
statistically significant reductions in mean hemoglobin (both sexes), mean
hematocrit and red blood cell levels (both sexes), and mean reticulocyte
levels (males only) at the 5.0 mg/kg/day dose or higher after 7 weeks. There
were also statistically significant reductions in liver enzymes LDH, SGOT,
SGPT, and alkaline phosphatase at week 14 in animals treated at the 15.0
mg/kg/day or higher doses. Kidney weights (absolute and relative) showed
statistically significant increases in all animals at the 15.0 mg/kg/day dose
or higher at the end of the experimental protocol. Histopathologic
examinations correlated well with kidney organ weight changes showing cortical
and subcortical pathology. Increases in ovarian weights, T-4 levels, and a
decrease in BUN were reported, but were not considered to be treatment-
related.
In a second part of this study (Dow Chemical Co., 1983), B6C3F1 mice
(20/sex/group) were fed the diet chow mixed with 97.5% pure 2,4-D at 0.0, 5.0,
15.0, 45.0 or 90.0 mg/kg bw/day (calculated doses) for 91 days. Criteria used
to determine toxicity were the same as for rats. The only effect reported at
5 mg/kg/day was increased weight of adrenals in females. Effects at 15
mg/kg/day included altered organ weights and hematologic effects. Kidney
weights were not affected below 45 mg/kg/day.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — The 100-fold uncertainty factor accounts for both interspecies and
interhuman variability in the toxicity of this chemical in lieu of specific
data. Because an analysis of the 90-day and 1-year interim results suggests
that the NOAEL would hold for the full 2-year duration, inclusion of the
subchronic-to-chronic UF is not warranted.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
The subchronic studies previously discussed provide a more sensitive basis for the RfD than available chronic or reproduction studies. Chronic toxicity and reproduction studies of 2,4-D indicated no adverse effects at dietary levels up to 500 ppm in dogs (approximately 14.5 mg/kg bw/day), up to 1250 ppm in rats (approximately 62.5 mg/kg bw/day) (Hansen et al., 1971), or at levels of 1000 ppm in drinking water (50-100 mg/kg bw/day) in pregnant rats (exposed through gestation and for 10 months following parturition) or their offspring (exposed for up to 2 years after weaning) (Bjorklund and Erne, 1966). A secondary reference to another study reported an increase in mortality among rats whose dams received approximately 50 mg/kg bw/day of 2,4-D in the diet for 3 months before mating and throughout gestation and lactation (Gaines and Kimbrough, 1970).
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Medium
RfD — Medium
Confidence in the principal study is medium because a fair number of animals of each sex was used, four doses were given, and a good number of parameters were measured. Confidence in the database is medium because several studies support both the observation of critical toxic effects and the levels at which they occur. Medium confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — U.S. EPA, 1984
This document has received several internal EPA reviews, reviews by outside
expert scientists and a public review.
Other EPA Documentation — None
Agency Work Group Review — 05/20/1985, 02/05/1986
Verification Date — 02/05/1986
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfD for 2,4-Dichlorophenoxyacetic acid (2,4-D) conducted in November 2001 identified one or more significant new studies. IRIS users may request the references for those studies from the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
__I.A.7. EPA Contacts (Oral RfD)
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — 2,4-Dichlorophenoxyacetic acid (2,4-D)
CASRN — 94-75-7
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — 2,4-Dichlorophenoxyacetic acid (2,4-D)
CASRN — 94-75-7
This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — 2,4-Dichlorophenoxyacetic acid (2,4-D)
CASRN — 94-75-7
Last Revised — 08/01/1989
_VI.A. Oral RfD References
Bjorklund, N. and K. Erne. 1966. Toxicological studies of phenoxyacetic
herbicides in animals. Acta. Vet. Scand. 7: 364-390.
Dow Chemical Company. 1983. Accession No. 251473. Available from EPA.
Write to FOI, EPA, Washington, DC 20460.
Gaines, T. and R. Kimbrough. 1970. Personal Communication. (Cited in Hansen
et al., 1971).
Hansen, W.H., M.L. Quaife, R.T. Habermann and O.G. Fitzhugh. 1971. Chronic
toxicity of 2,4-dichlorophenoxyacetic acid in rats and dogs. Toxicol. Appl.
Pharmacol. 20(1): 122-129.
U.S. EPA. 1984. Drinking Water Criteria Document for 2,4-
Dichlorophenoxyacetic Acid (2,4-D). Prepared by the Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Drinking Water, Washington, DC.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — 2,4-Dichlorophenoxyacetic acid (2,4-D)
CASRN — 94-75-7
Date |
Section |
Description |
---|---|---|
09/30/1987 | IV. | Regulatory Action section on-line |
06/30/1988 | I.A. | RfD under review - change possible |
08/01/1989 | VI. | Bibliography on-line |
02/01/1990 | II. | Carcinogenicity assessment review status changed |
01/01/1992 | IV. | Regulatory actions updated |
08/01/1995 | I.A. | EPA's RfD/RfC and CRAVE workgroups were discontinued in May, 1995. Chemical substance reviews that were not completed by September 1995 were taken out of IRIS review. The IRIS Pilot Program replaced the workgroup functions beginning in September, 1995. |
04/01/1997 | III., IV., V. | Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information. |
12/03/2002 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — 2,4-Dichlorophenoxyacetic acid (2,4-D)
CASRN — 94-75-7
Last Revised — 03/31/1987
- 94-75-7
- ACETIC ACID, (2,4-DICHLOROPHENOXY)-
- ACIDE 2,4-DICHLORO PHENOXYACETIQUE
- ACIDO(2,4-DICLORO-FENOSSI)-ACETICO
- AGROTECT
- AMIDOX
- AMOXONE
- AQUA-KLEEN
- BH 2,4-D
- BRUSH-RHAP
- B-SELEKTONON
- CHLOROXONE
- CROP RIDER
- CROTILIN
- 2,4-D
- D 50
- DACAMINE
- 2,4-D ACID
- DEBROUSSAILLANT 600
- DECAMINE
- DED-WEED LV-69
- DESORMONE
- (2,4-DICHLOOR-FENOXY)-AZIJNZUUR
- DICHLOROPHENOXYACETIC ACID
- 2,4-Dichlorophenoxyacetic acid
- Dichlorophenoxyacetic acid, 2,4-
- 2,4-DICHLORPHENOXYACETIC ACID
- (2,4-DICHLOR-PHENOXY)-ESSIGSAEURE
- DICOPUR
- DICOTOX
- DINOXOL
- DMA-4
- DORMONE
- 2,4-DWUCHLOROFENOKSYOCTOWY KWAS
- EMULSAMINE BK
- EMULSAMINE E-3
- ENT 8,538
- ENVERT 171
- ENVERT DT
- ESTERON
- ESTERONE FOUR
- ESTONE
- FARMCO
- FERNESTA
- FERNIMINE
- FERNOXONE
- FERXONE
- FOREDEX 75
- FORMULA 40
- HEDONAL
- HERBIDAL
- IPANER
- KROTILINE
- LAWN-KEEP
- MACRONDRAY
- MIRACLE
- MONOSAN
- MOXONE
- NA 2765
- NETAGRONE
- NETAGRONE 600
- NSC 423
- PENNAMINE
- PENNAMINE D
- PHENOX
- PIELIK
- PLANOTOX
- PLANTGARD
- RCRA WASTE NUMBER U240
- RHODIA
- SALVO
- SPRITZ-HORMIN/2,4-D
- SPRITZ-HORMIT/2,4-D
- TRANSAMINE
- TRIBUTON
- TRINOXOL
- U 46DP
- U-5043
- VERGEMASTER
- VIDON 638
- VISKO-RHAP
- WEED-AG-BAR
- WEEDAR-64
- WEEDATUL
- WEED-B-GON
- WEEDEZ WONDER BAR
- WEEDONE LV4
- WEED-RHAP
- WEED TOX
- WEEDTROL