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1,2,3-Trichloropropane
CASRN 96-18-4

Contents


0200
1,2,3-Trichloropropane; CASRN 96-18-4  


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  1,2,3-Trichloropropane

File On-Line 03/31/1987

Category (section)                           Status      Last Revised
-----------------------------------------    --------    ------------

Oral RfD Assessment (I.A.)                   on-line       08/01/1990

Inhalation RfC Assessment (I.B.)             no data     

Carcinogenicity Assessment (II.)             no data       11/01/1993



_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS __I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD) Substance Name -- 1,2,3-Trichloropropane CASRN -- 96-18-4 Last Revised -- 08/01/1990 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 -------------------- ----------------------- ----- --- --------- Alterations in NOAEL: 8 mg/kg/day, 5 1000 1 6E-3 clinical chemistry days/week converted mg/kg/day and reduction in red to 5.71 mg/kg/day cell mass LOAEL: 16 mg/kg/day, Rat Oral Subchronic 5 days/week converted Study to 11.4 mg/kg/day NTP, 1983
*Conversion Factors: Doses adjusted for dosing schedule (5 days/week) ___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD) NTP (National Toxicology Program). 1983. 120-Day gavage study in mice and rats with 1,2,3-trichloropropane. Unpublished report prepared by Hazleton Laboratories. In this study, the toxic effects of 1,2,3-trichloropropane in B6C3F1 mice and Fischer 344 rats were examined following administration of the test material by gavage 5 days/week for 60 to 120 days. Groups of 20 animals/sex (mice or rats) were administered doses of 8, 16, 32, 63, 125, or 250 mg/kg/day trichloropropane in corn oil. The control animals (30/sex) received corn oil by gavage. After 60 days, 50% of the animals for each test group and 10 mice/sex and 10 rats/sex from the control group were sacrificed. Clinical pathology and histopathology were performed after 60 and 120 days. Several other parameters, such as body weight changes, food consumption, mortality and organ weight changes, were also recorded. Treatment-related deaths occurred at the 250 mg/kg/day dose level in both mice and rats during the early phase of the study. Rats were more sensitive than mice; the mortality rate was 100% in rats. Other chemical-related findings common to both mice and rats were increased liver and kidney weights accompanied by histopathological changes in the organs. Additionally, rats showed decreased body weight gains, alterations in serum enzymes associated with hepatic and renal toxicity, and decreased red cell mass. Female rats and mice as contrasted with males showed increased sensitivity to trichloropropane. Specifically, treatment-related clinical chemistry alterations were observed in male rats receiving doses of 125 and 63 mg/kg/day, whereas females showed alterations in the same parameters at doses of 125, 63 and 32 mg/kg/day and, to a lesser extent, at the 16 mg/kg/day level. Based on data reported in this study, LOAELs were 63 mg/kg/day for mice and 16 mg/kg/day for rats. The highest NOEL was 8 mg/kg/day, 5 days/week or 5.7 mg/kg/day (on 5 days/7 days basis) in rats. Applying an uncertainty factor of 1000, an RfD of 0.006 mg/kg/day or 0.4 mg/day for a 70-kg person can be derived. ___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD) UF -- An uncertainty factor of 1000 was used; 10 for intraspecies, 10 for interspecies extrapolation, and 10 for extrapolating subchronic to chronic exposures. MF -- None ___I.A.4. ADDITIONAL COMMENTS (ORAL RfD) Other than LD50 data for trichloropropane derived from oral studies and several short-term inhalation studies published as abstracts, no chronic or reproductive studies are available for quantitative risk analysis. ___I.A.5. CONFIDENCE IN THE ORAL RfD Study -- High Data Base -- Low RfD -- Low The principal study was well-designed, established a NOEL and LOAEL, and measured several toxicological endpoints in both mice and rats; therefore, a high confidence was recommended. The data base lacks pertinent supporting inhalation or oral studies; therefore, a low confidence was recommended. Confidence in the RfD can be considered low to medium. ___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 -- 05/14/1986, 09/02/1986 Verification Date -- 09/02/1986 ___I.A.7. EPA CONTACTS (ORAL RfD) Please contact the Risk Information Hotline for all questions concerning this assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX) or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC) Substance Name -- 1,2,3-Trichloropropane CASRN -- 96-18-4 Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE Substance Name -- 1,2,3-Trichloropropane CASRN -- 96-18-4 Not available at this time.
_VI. BIBLIOGRAPHY Substance Name -- 1,2,3-Trichloropropane CASRN -- 96-18-4 Last Revised -- 08/01/1990 __VI.A. ORAL RfD REFERENCES NTP (National Toxicology Program). 1983. 120-Day gavage study in mice and rats with 1,2,3-trichloropropane. Unpublished report prepared by Hazleton Laboratories.
__VI.B. INHALATION RfD REFERENCES None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES None
_VII. REVISION HISTORY Substance Name -- 1,2,3-Trichloropropane CASRN -- 96-18-4 -------- -------- -------------------------------------------------------- Date Section Description -------- -------- -------------------------------------------------------- 03/01/1988 I.A.1. Principal study corrected 03/01/1988 I.A.5. Confidence levels revised 06/01/1990 IV.F.1. EPA contact changed 06/01/1990 VI. Bibliography on-line 08/01/1990 I.A. Text edited 08/01/1990 III.A. Health Advisory on-line 08/01/1990 VI.D. Health Advisory references added 01/01/1992 I.A.7. Primary contact changed 01/01/1992 IV. Regulatory actions updated 07/01/1992 II. Carcinogen assessment summary now under review 03/01/1993 II. Work group review date added 11/01/1993 II. Work group review date added
VIII. SYNONYMS Substance Name -- 1,2,3-Trichloropropane CASRN -- 96-18-4 Last Revised -- 03/31/1987 96-18-4 ALLYL TRICHLORIDE GLYCEROL TRICHLOROHYDRIN GLYCERYL TRICHLOROHYDRIN NCI-C60220 PROPANE, 1,2,3-TRICHLORO- TRICHLOROHYDRIN 1,2,3-Trichloropropane Trichloropropane, 1,2,3-



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Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0200.HTM