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2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) (CASRN 93-76-5)

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0262

2,4,5-Trichlorophenoxyacetic acid (2,4,5-T); CASRN 93-76-5

Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data, as outlined in the IRIS assessment development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached during the assessment development process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website.

STATUS OF DATA FOR 2,4,5-T

File First On-Line 09/07/1988

Category (section)
Status
Last Revised
Oral RfD Assessment (I.A.) on-line 06/01/1989
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 — 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
CASRN — 93-76-5
Last Revised — 06/01/1989

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.

__I.A.1. Oral RfD Summary

Critical Effect
Experimental Doses*
UF
MF
RfD

Increased urinary
coproporphyrins

2-Year Rat Feeding
Study

Kociba et al., 1979

Reduced neonatal
survival

3-Generation Rat
Feeding Study

Smith et al., 1981

NOAEL: 3 mg/kg/day

LOAEL: 10 mg/kg/day

300
1
1E-2
mg/kg/day

*Conversion Factors -- None

__I.A.2. Principal and Supporting Studies (Oral RfD)

Kociba, R.J., D.G. Keyes, R.W. Lisowe, et al. 1979. Results of a two-year chronic toxicity and oncogenic study of rats ingesting diets containing 2,4,5- trichlorophenoxyacetic acid (2,4,5-T). Food Cosmet. Toxicol. 17: 205-221.

Smith, F.A., F.J. Murray, J.A. John, et al. 1981. Three-generation reproduction study of rats ingesting 2,4,5-trichloropenoxyacetic acid in the diet. Toxicol. Res. Lab., Dow Chemical, Midland, MI.

Groups of Sprague-Dawley rats (50/sex) were maintained on diets supplying 0, 3, 10, or 30 mg 2,4,5-T/kg bw/day for 2 years (Kociba et al., 1979). An additional 10 animals/sex/group were sacrificed after 4 months. Toxicological endpoints measured were body weight, food consumption, tumorigenicity, hematology, urinalysis, serum chemistry and histopathology. No effects were observed at 3 mg/kg/day. An increase in urinary excretion of coproporphyrins (at 4 months only) was reported for males at 10 and 30 mg/kg/day, and for females only at the high-dose level. A mild dose-related increase in the incidence of mineralized deposits in the renal pelvis was reported for females at 10 and 30 mg/kg/day after 2 years.

In a 3-generation reproduction study (Smith et al.,1981), rats were fed levels of 2,4,5-T corresponding to 0, 3, 10, or 30 mg/kg bw/day. No effects were observed at the low dose. Reduced neonatal survival was observed at both higher doses.

The reproductive endpoint is well documented. Other studies have shown effect on reproduction in mice, rats, hamsters and monkeys. A LOAEL of 15 mg/kg with a NOEL of 8 mg/kg for reduced fetal body weight was reported for mice. Fetal mortality was observed following administration of 2,4,5-T at 40 mg/kg (highest dose) to pregnant hamsters. Cleft palate was induced in A/JAX mice at 15 mg/kg; lower doses were not tested (Cranmer, 1978). Other strains of mice were less sensitive. Higher doses (about 200 mg/kg) induce frank teratogenic effects in rats. A qualitative association between 2,4,5-T exposure and human birth defects has been suggested. Terata and fetotoxic effects have not been observed in monkeys up to a dose of 40 mg/kg.

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF — The UF of 300 includes uncertainty in the extrapolation of dose levels from laboratory animals to humans (10A), uncertainty in the threshold for sensitive humans (10H), and uncertainty because of deficiencies in the chronic toxicity database (3D).

MF — None

__I.A.4. Additional Studies/Comments (Oral RfD)

None

__I.A.5. Confidence in the Oral RfD

Study — High
Database — Medium
RfD — Medium

The Smith et al. (1981) study appears to be adequate for the assessment of long-term reproductive effects; a clear NOEL is established. The database is highly supportive of both the nature and the magnitude of the reproductive effect. The Kociba et al. (1979) study rates a high confidence rating because of its relative completeness. Confidence in the RfD is medium (tending towards high) because of the mutual support of the two studies and strength of the reproductive database. The relative weakness of the chronic toxicity database precludes a higher confidence level.

__I.A.6. EPA Documentation and Review of the Oral RfD

Source Docment -- U.S. EPA, 1982

Other EPA Documentation — None

Agency Work Group Review — 12/18/1985, 05/15/1986, 08/13/1987, 10/15/1987, 01/20/1988

Verification Date — 01/20/1988

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 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) conducted in August 2003 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).

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_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
CASRN — 93-76-5

Not available at this time.

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_II.  Carcinogenicity Assessment for Lifetime Exposure

Substance Name — 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
CASRN — 93-76-5

This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.

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_III.  [reserved]
_IV.  [reserved]
_V.  [reserved]


_VI.  Bibliography

Substance Name — 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
CASRN — 93-76-5
Last Revised — 02/01/1993

_VI.A. Oral RfD References

Cranmer, M. 1978. Use of herbicides in forestry. USDA/EPA Symposium, Arlington, VA, February 21-22,.

Kociba, R.J., D.G. Keyes, R.W. Lisowe, et al. 1979. Results of a two-year chronic toxicity and oncogenic study of rats ingesting diets containing 2,4,5- trichlorophenoxyacetic acid (2,4,5-T). Food Cosmet. Toxicol. 17: 205-221.

Smith, F.A., F.J. Murray, J.A. John, K.D. Nitschke, R.J. Kociba and B.A. Schwetz. 1981. Three-generation reproduction study of rats ingesting 2,4,5- trichlorophenoxyacetic acid in the diet. Toxicol. Res. Lab., Dow Chemical, Midland, MI.

U.S. EPA. 1982. Draft Interim Criterion Statement: Chlorophenoxy Herbicides. Ambient Water Quality Criterion for the Protection of Human Health. ECAO-CIN- 82-D005. (Internal Review Draft). This document was developed from a multimedia document on the Chlorophenoxy Herbicides which during 1982 had fairly comprehensive external review with a limited internal review.

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_VI.B. Inhalation RfD References

None

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_VI.C. Carcinogenicity Assessment References

None

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_VII.  Revision History

Substance Name — 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
CASRN — 93-76-5

Date
Section
Description
09/07/1988 I.A. Oral RfD summary on-line
01/01/1989 I.A.7. Contacts phone numbers corrected
06/01/1989 I.A.6. Work group review dates added
08/01/1989 VI. Bibliography on-line
08/01/1989 Synonyms Silvex deleted from synonyms
01/01/1992 I.A.7. Secondary contact changed
01/01/1992 IV. Regulatory Action section on-line
02/01/1993 III.A. Health Advisory on-line
02/01/1993 VI.D. Health Advisory references on-line
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
10/28/2003 I.A.6 Screening-Level Literature Review Findings message has been added.

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_VIII.  Synonyms

Substance Name — 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
CASRN — 93-76-5
Last Revised — 08/01/1989

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