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