1,2,3-Trichloropropane (CASRN 96-18-4) | IRIS
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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 First 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 Rat Oral Subchronic NTP, 1983 |
NOAEL: 8 mg/kg/day, 5 LOAEL: 16 mg/kg/day, |
1000
|
1
|
6E-3
mg/kg/day |
*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 Unpublished report prepared by Hazleton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 Studies/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
Database — 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 database 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
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 1,2,3-Trichloropropane 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 — 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.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_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 RfC 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 |
08/01/1995 | II. | EPA's RfD/RfC and CRAVE workgroups were discontinued in May, 1995. Chemical substance reviews that were not completed by September 1995 were taken out of IRIS review. The IRIS Pilot Program replaced the workgroup functions beginning in September, 1995. |
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. |
07/30/2003 | I., II. | This chemical is being reassessed under the IRIS Program. |
_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-