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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
clinical chemistry
and reduction in red
cell mass

Rat Oral Subchronic
Study

NTP, 1983

NOAEL: 8 mg/kg/day, 5
days/week converted
to 5.71 mg/kg/day

LOAEL: 16 mg/kg/day,
5 days/week converted
to 11.4 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).

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_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — 1,2,3-Trichloropropane
CASRN — 96-18-4

Not available at this time.

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_II.  Carcinogenicity Assessment for Lifetime Exposure

Substance Name — 1,2,3-Trichloropropane
CASRN — 96-18-4

Not available at this time.

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_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.

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_VI.B. Inhalation RfC References

None

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_VI.C. Carcinogenicity Assessment References

None

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_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.

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_VIII.  Synonyms

Substance Name — 1,2,3-Trichloropropane
CASRN — 96-18-4
Last Revised — 03/31/1987

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