1,1,2-Trichloropropane (CASRN 598-77-6)
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0372
1,1,2-Trichloropropane; CASRN 598-77-6
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 1,1,2-Trichloropropane
File First On-Line 09/26/1988
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 09/26/1988* |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
*A comprehensive review of toxicological studies was completed (2004) - please see section I.A.6 for more information.
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — 1,1,2-Trichloropropane
CASRN — 598-77-6
Last Revised — 09/26/1988
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.
__I.A.1. Oral RfD Summary
Critical Effect
|
Experimental Doses* |
UF |
MF
|
RfD
|
---|---|---|---|---|
Mild lesions in Rat Oral Subchronic Villeneuve et al., |
NOEL: 100 mg/L in LOAEL: 1000 mg/L |
3000
|
1
|
5E-3
mg/kg/day |
*Conversion Factors: The equivalent dosages were estimated by the investigators.
__I.A.2. Principal and Supporting Studies (Oral RfD)
Villeneuve, D.C., I. Chu, V.E. Secours, M.G. Cotie, G.L. Plaa and V.E. Valli. 1985. Results of a 90-day toxicity study on 1,2,3- and 1,1,2-trichloropropane administered via the drinking water. Sci. Total Environ. 47: 421-426.
1,1,2-Trichloropropane (dissolved in Emulphor) was administered to groups of 10 male and 10 female weanling Sprague-Dawley rats in the drinking water at concentrations of 1, 10, 100 or 1000 mg/L for 90 days. These concentrations were equivalent to 0.15, 1.5, 15.0, or 150 mg/kg/day for males and 0.20, 2.0, 20.3, and 203 mg/kg/day for females as determined by the investigators. Two control groups consisted of 10 rats/sex each: one group received tap water, the other received tap water plus Emulphor. Parameters evaluated were clinical appearance, body weight, water consumption, hematology, clinical chemistry, hepatic mixed-function oxidase activity and organ weights. Histological examinations of major organs and tissues were also performed.
There were no effects on water consumption, body weight gain, hematological parameters or enzyme activity. One male at 1000 mg/L and one female at 100 mg/L died of undetermined causes. At 1000 mg/L, males had increased liver weights and females had increased serum cholesterol levels. Histopathological lesions included anisokaryosis and fatty vacuolization in the liver; eosinophilic inclusions, pyknosis, nuclear displacement and glomerular adhesions in the kidney; and follicular collapse, reduction in colloid density and increased epithelial cell height in the thyroid. The lesions were considered mild and occurred only in the 1000 mg/L group. Thus, 1000 mg/L (150 mg/kg/day for males) is the LOAEL and 100 mg/L (15 mg/kg/day for males) is the highest NOAEL.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — The UF of 3000 allows for uncertainty in the extrapolation of dose levels from laboratory animals to humans (10A), variability in sensitivity among humans (10H), uncertainty in extrapolating from subchronic to chronic exposure (10S), and uncertainty because of the lack of studies assessing reproductive or developmental effects (3D).
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
1,1,2-Trichloropropane has not been studied for teratogenicity or other reproductive effects or chronic toxicity. Smyth et al. (1962) reported an oral LD50 of 1.23 g/kg for rats. An inhalation exposure to 1,1,2- trichloropropane at 2000 ppm (12 g/cu.m) for 4 hours killed three of six rats. The dermal LD50 in rabbits was 14.1 mL/kg.
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Low
RfD — Low
Confidence in the study is medium because although it was a well-conducted study by a relevant route and defined both a NOAEL and a LOAEL, only 10 rats/group were used in this subchronic study. As there are no supporting studies, confidence in the database and the RfD is low.
__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — U.S. EPA, 1987
Limited peer review and extensive Agency-wide review 1987.
Other EPA Documentation — None
Agency Work Group Review — 09/17/1987
Verification Date — 09/17/1987
A comprehensive review of toxicological studies published prior to 2004 was conducted. No new health effects data were identified that would be directly useful in the revision of the existing RfD for 1,1,2-Trichloropropane and a change in the RfD is not warranted at this time.
__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 — 1,1,2-Trichloropropane
CASRN — 598-77-6
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — 1,1,2-Trichloropropane
CASRN — 598-77-6
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 — 1,1,2-Trichloropropane
CASRN — 598-77-6
Last Revised — 08/01/1991
_VI.A. Oral RfD References
Smyth, H.F., C.P. Carpenter, C.S. Weil, U.C. Pozzani and J.A. Striegel. 1962. Range-finding toxicity data: List VI. Ind. Hyg. J. 23: 95-107.
U.S. EPA. 1987. Health and Environmental Effects Document on Trichloropropanes. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response, Washington, DC.
Villeneuve, D.C., I. Chu, V.E. Secours, M.G. Cotie, G.L. Plaa and V.E. Valli. 1985. Results of a 90-day toxicity study on 1,2,3- and 1,1,2-trichloropropane administered via the drinking water. Sci. Total Environ. 47: 421-426.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — 1,1,2-Trichloropropane
CASRN — 598-77-6
Date |
Section |
Description |
---|---|---|
09/26/1988 | I.A. | Oral RfD summary on-line |
08/01/1991 | VI. | Bibliography 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. |
09/29/2004 | I.A.6. | Screening-Level Literature Review Findings message has been removed and replaced by comprehensive literature review conclusions. |
_VIII. Synonyms
Substance Name — 1,1,2-Trichloropropane
CASRN — 598-77-6
Last Revised — 09/26/1988
- 598-77-6
- PROPANE, 1,1,2-TRICHLORO-
- 1,1,2-Trichloropropane
- Trichloropropane, 1,1,2-