|
o-Chlorotoluene
CASRN 95-49-8
Contents
0412
o-Chlorotoluene; CASRN 95-49-8
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 o-Chlorotoluene
File On-Line 02/01/1990
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 02/01/1990
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- o-Chlorotoluene
CASRN -- 95-49-8
Last Revised -- 02/01/1990
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
-------------------- ----------------------- ----- --- ---------
Decrease in body NOAEL: 20 mg/kg/day 1000 1 2E-2
weight gain mg/kg/day
LOAEL: 80 mg/kg/day
15-Week Rat Study
Oral Exposure (gavage)
Gibson et al., 1974a
*Conversion Factors: none
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Gibson, W.R., F.O. Gossett, G.R. Koenig and F. Marroquin. 1974a. The
toxicity of daily oral doses of o-chlorotoluene in the rat. Toxicology
Division, Lilly Research Laboratories. Submitted to Test Rules Development
Branch, Office of Toxic Substances, U.S. EPA, Washington, D.C.
o-Chlorotoluene in an aqueous solution containing 5% acacia as the emulsifying
agent was administered by gavage to weanling Harlan rats (20 males and 20
females/group) at doses of 0, 20, 80, or 320 mg/kg/day for 103 or 104 days.
At doses of 80 and 320 mg/kg/day, male rats developed a statistically
significant decrease in mean body weight gain (15% and 22%, respectively) and
an increase in adrenal weight. Increased heart and testes weights, an
increase in white blood cell (WBC) count, and a decrease in prothrombin time
were observed in males at the 320 mg/kg/day dose level. At the 80 mg/kg/day
dose, blood urea nitrogen (BUN) was increased in males. No histological
changes related to intake of o-chlorotoluene were seen in this study. A NOAEL
of 20 mg/kg/day is indicated and the LOAEL is 80 mg/kg/day.
Adult male and female beagle dogs (four/sex/level) were given gelatin capsules
containing an aqueous emulsion of o-chlorotoluene in 5% acacia at doses of 0,
5, 20, or 80 mg/kg/day daily for 97 days (Gibson et al., 1974b). At 1, 2, and
4 weeks and at 2 and 3 months, the dogs were examined for hematological and
biochemical changes, as well as for changes in urinalyses. No changes were
observed in body weight nor were any histological changes evident. Females
treated at the 80 mg/kg/day dose level developed a transient increase in
platelet count which returned to normal after 14 weeks of exposure. Since the
effects were transient, the authors did not consider the increased platelet
count to be treatment related. A NOAEL of 80 mg/kg/day is indicated for dogs
in this study.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty factor of 1000 was used: 10 to account for interspecies
extrapolation, 10 for differences in individual human sensitivity, and 10 for
use of a subchronic study.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
No oral reproductive or developmental toxicity studies are available.
Huntingdon Research Center (1983a,b) exposed rats (25 animals/dose) and
rabbits (16 animals/dose) to o-chlorotoluene vapor for 6 hours/day during days
6 to 19 (rats) and 6 to 28 (rabbits) of gestation. In rats, there was an
increase in malformed fetuses at doses of 9000 mg/cu.m (1710 mg/kg/day), but
not at 1000 mg/cu.m (190 mg/kg/day) and 3000 mg/cu.m (570 mg/kg/day); the
authors concluded that malformations in one fetus at the 1000 mg/cu.m dose
were not related to treatment. In rabbits, no fetal effects were observed at
doses of 1500 (150), 4000 (400) and 15,000 mg/cu.m (1500 mg/kg/day).
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- Low
RfD -- Low
The confidence in the study is medium because of the number of animals and
doses used and because several parameters were studied. The confidence in the
data base is low since no specific pattern of toxicity was observed at the
higher doses. Considering no chronic or pertinent oral reproductive or
developmental data are available, the overall confidence in the RfD is rated
low.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- U.S. EPA, 1985
Other EPA Documentation -- None
Agency Work Group Review -- 07/20/1989, 09/21/1989
Verification Date -- 09/21/1989
___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 -- o-Chlorotoluene
CASRN -- 95-49-8
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- o-Chlorotoluene
CASRN -- 95-49-8
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- o-Chlorotoluene
CASRN -- 95-49-8
Last Revised -- 08/01/1990
__VI.A. ORAL RfD REFERENCES
Gibson, W.R., F.O. Gossett, G.R. Koenig and F. Marroquin. 1974a. The
toxicity of daily oral doses of o-chlorotoluene in the rat. Toxicology
Division, Lilly Research Laboratories. Submitted to Test Rules Development
Branch, Office of Toxic Substances, U.S. EPA, Washington, DC.
Gibson, W.R., F.O. Gossett, G.R. Koenig and F. Marroquin. 1974b. The
toxicity of daily oral doses of o-chlorotoluene in the dog. Toxicology
Division, Lilly Research Laboratories. Submitted to Test Rules Development
Branch, Office of Toxic Substances, U.S. EPA, Washington, DC.
Huntingdon Research Center. 1983a. Effect of 2-chlorotoluene vapour on
pregnancy of the rat. Submitted to Test Rules Development Branch, Office of
Toxic Substances, U.S. EPA, Washington, DC.
Huntingdon Research Center. 1983b. Effect of 2-chlorotoluene vapour on
pregnancy of the New Zealand White rabbit. Submitted to Test Rules
Development Branch, Office of Toxic Substances, U.S. EPA, Washington, DC.
U.S. EPA. 1985. Health and Environmental Effects Profile for Chlorotoluene
(o-, m-, p-). 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.
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- o-Chlorotoluene
CASRN -- 95-49-8
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
02/01/1990 I.A. Oral RfD summary on-line
02/01/1990 VI. Bibliography on-line
08/01/1990 III.A. Health Advisory on-line
08/01/1990 VI.D. Health Advisory references added
01/01/1992 IV. Regulatory Action section on-line
VIII. SYNONYMS
Substance Name -- o-Chlorotoluene
CASRN -- 95-49-8
Last Revised -- 02/01/1990
95-49-8
AI3-15912 [USDA]
BENZENE, 1-CHLORO-2-METHYL- (9CI)
1-CHLORO-2-METHYLBENZENE
2-CHLORO-1-METHYLBENZENE
2-CHLOROTOLUENE
O-CHLOROTOLUENE
ORTHO-CHLOROTOLUENE
HSDB 5291
1-METHYL-2-CHLOROBENZENE
2-METHYLCHLOROBENZENE
TOLUENE, O-CHLORO- (8CI)
O-TOLYL CHLORIDE
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0412.HTM
|
