2,4-Dimethylphenol (CASRN 105-67-9)
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0466
2,4-Dimethylphenol; CASRN 105-67-9
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-Dimethylphenol
File First On-Line 11/01/1990
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 11/01/1990 |
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-Dimethylphenol
CASRN — 105-67-9
Last Revised — 11/01/1990
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
|
---|---|---|---|---|
Clinical signs Mouse Subchronic Oral Gavage U.S. EPA, 1989 |
NOAEL: 50 mg/kg/day LOAEL: 250 mg/kg/day |
3000
|
1
|
2E-2
mg/kg/day |
* Conversion Factors: None
__I.A.2. Principal and Supporting Studies (Oral RfD)
U.S. EPA. 1989. Ninety-day gavage study in Albino mice using 2,4- dimethylphenol. Study No. 410-2831, prepared by Dynamac Corporation, Rockville, MD, for the Office of Solid Waste and Emergency Response, Washington, DC.
2,4-Dimethylphenol was administered daily to male and female albino mice by gavage. The animals (30/sex/group) were dosed for 90 days with 5.0, 50.0, or 250 mg 2,4-dimethylphenol/kg/day. Two control groups, untreated and vehicle (corn oil), of similar size were also established. Effects examined included mortality, clinical signs, body weights, food consumption, opthalmology, hematology and clinical chemistry, organ weights, and gross histopathology. Although 15 deaths occurred during this study (mostly because of errors in technical procedure), only one was considered as possibly treatment-related: a male in the 5 mg/kg/day-dose group died during the first 30 days of the experiment. No significant differences were found between treated and vehicle control groups in mean body weight, body weight gains, food consumption, or eye examinations at any dosage. Toxicologically relevant clinical signs observed only after week 6 in the high-dose groups of both genders included: squinting, lethargy, prostration, and ataxia, with onset shortly after dosing. Statistically significant hematological changes (p<0.05) included lower mean corpuscular volume and mean corpuscular hemoglobin concentration in females at terminal, but not interim, sacrifice.
At interim sacrifice in female mid- and high-dose groups, blood urea nitrogen (BUN) levels were significantly below vehicle controls; whereas at final sacrifice in the female mid-dose group, BUN levels were significantly higher than vehicle controls. Low-dose males at interim sacrifice had significantly higher cholesterol levels. Significant differences were not found in gross necropsy or histopathological evaluations, or in organ weights, except for an increase in adrenal weights of low-dose females. The LOAEL and NOAEL for this study were 250 and 50 mg/kg/day, respectively.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 3000 was established: 10 each for inter- and intraspecies variability and 30 for lack of chronic toxicity data, data in a second species and reproductive/developmental studies.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
A 14-day gavage study with 2,4-dimethylphenol conducted by the same laboratory that conducted the principal study, revealed lethargy, prostration, and ataxia in males and females in the 250 mg/kg/day-dose group, the same dose at which effects were found in the principal study (U.S. EPA, 1987).
No other long-term toxicity, reproductive, or developmental studies of 2,4- dimethylphenol were found in the databases searched. Literature concerning 2,6-dimethylphenol was identified, but an SAR-based RfD is considered inappropriate when a valid long-term toxicity study for 2,4-dimethylphenol is available.
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Low
RfD — Low
Confidence in the study is medium, since it examined appropriate endpoints and identified both a LOAEL and a NOAEL. The results of this study are consistent with those of a 14-day gavage study. The database provides no information on chronic and reproductive studies. Low confidence in both the database and oral RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — This assessment is not presented in any existing U.S. EPA document.
Other EPA Documentation — None
Agency Work Group Review — 02/21/1990
Verification Date — 02/21/1990
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-Dimethylphenol conducted in September 2002 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-Dimethylphenol
CASRN — 105-67-9
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — 2,4-Dimethylphenol
CASRN — 105-67-9
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-Dimethylphenol
CASRN — 105-67-9
Last Revised — 11/01/1990
_VI.A. Oral RfD References
U.S. EPA. 1987. Fourteen-day gavage study in Albino mice using 2,4- dimethylphenol. Study No. 410-2830, prepared by Dynamac Corporation, Rockville, MD for the Office of Solid Waste and Emergency Response, Washington, DC.
U.S. EPA. 1989. Ninety-day gavage study in Albino mice using 2,4- dimethylphenol. Study No. 410-2831, prepared by Dynamac Corporation, Rockville, MD, for the Office of Solid Waste and Emergency Response, Washington, DC.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — 2,4-Dimethylphenol
CASRN — 105-67-9
Date |
Section |
Description |
---|---|---|
11/01/1990 | I.A. | Oral RfD summary on-line |
11/01/1990 | VI. | Bibliography on-line |
01/01/1992 | IV. | Regulatory Action section 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. |
12/03/2002 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — 2,4-Dimethylphenol
CASRN — 105-67-9
Last Revised — 11/01/1990
- 105-67-9
- Phenol, 2,4-dimethyl-
- Caswell No. 907A
- EPA Pesticide Chemical Code 086804
- HSDB 4253
- m-XYLENOL
- NSC 3829
- RCRA WASTE NUMBER U101
- 1-HYDROXY-2,4-DIMETHYLBENZENE
- 2,4-dimethylphenol
- 2,4-Xylenol
- 4-HYDROXY-1,3-DIMETHYLBENZENE
- 4,6-DIMETHYLPHENOL