United States
Environmental Protection
1=1 m m Agency
EPA/690/R-09/064F
Final
9-11-2009
Provisional Peer-Reviewed Toxicity Values for
1,2,3 -Trichlorobenzene
(CASRN 87-61-6)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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COMMONLY USED ABBREVIATIONS
BMD
Benchmark Dose
IRIS
Integrated Risk Information System
IUR
inhalation unit risk
LOAEL
lowest-observed-adverse-effect level
LOAELadj
LOAEL adjusted to continuous exposure duration
LOAELhec
LOAEL adjusted for dosimetric differences across species to a human
NOAEL
no-ob served-adverse-effect level
NOAELadj
NOAEL adjusted to continuous exposure duration
NOAELhec
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-ob served-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
RfC
inhalation reference concentration
RfD
oral reference dose
UF
uncertainty factor
UFa
animal to human uncertainty factor
UFC
composite uncertainty factor
UFd
incomplete to complete database uncertainty factor
UFh
interhuman uncertainty factor
UFl
LOAEL to NOAEL uncertainty factor
UFS
subchronic to chronic uncertainty factor
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PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR
1,2,3-TRICHLOROBENZENE (CASRN 87-61-6)
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (U.S. EPA) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1)	U.S. EPA's Integrated Risk Information System (IRIS).
2)	Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in U.S. EPA's Superfund
Program.
3)	Other (peer-reviewed) toxicity values, including
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in U.S. EPA's IRIS. PPRTVs are developed according to a
Standard Operating Procedure (SOP) and are derived after a review of the relevant scientific
literature using the same methods, sources of data, and Agency guidance for value derivation
generally used by the U.S. EPA IRIS Program. All provisional toxicity values receive internal
review by two U.S. EPA scientists and external peer review by three independently selected
scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multiprogram consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all U.S. EPA programs, while PPRTVs are developed
specifically for the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a 5-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV documents conclude that
a PPRTV cannot be derived based on inadequate data.
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and Resource Conservation and Recovery Act (RCRA) program offices are advised to
carefully review the information provided in this document to ensure that the PPRTVs used are
appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility
in question. PPRTVs are periodically updated; therefore, users should ensure that the values
contained in the PPRTV are current at the time of use.
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It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV document and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the U.S. EPA
Office of Research and Development's National Center for Environmental Assessment,
Superfund Health Risk Technical Support Center for OSRTI. Other U.S. EPA programs or
external parties who may choose of their own initiative to use these PPRTVs are advised that
Superfund resources will not generally be used to respond to challenges of PPRTVs used in a
context outside of the Superfund Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the U.S. EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
IRIS (U.S. EPA, 2009a), the Health Effects Assessment Summary Tables (HEAST;
U.S. EPA, 1997), and the Drinking Water Standards and Health Advisories list (U.S. EPA, 2006)
do not report noncancer or cancer assessments for 1,2,3-trichlorobenzene. The Chemical
Assessments and Related Activities (CARA) list (U.S. EPA, 1991, 1994) includes a Drinking
Water Criteria Document (DWCD) for Trichlorobenzenes (U.S. EPA, 1988) and a Health
Assessment Document (HAD) for Chlorinated Benzenes (U.S. EPA, 1985), neither of which
derived toxicity values for 1,2,3-trichlorobenzene due to inadequate data. The World Health
Organization (WHO) calculated a tolerable daily intake (TDI) of 0.02 mg/kg-day for
1,2,3-trichlorobenzene in an Environmental Health Criteria document (WHO, 1991), based on a
NOEL reported as 7.7 mg/kg-day in a 13-week dietary study in rats (Cote et al., 1988), to which
an UF of 500 was applied (basis for UF not reported). Health Canada (1993) derived a TDI of
0.00077 mg/kg-day using the same NOEL as the WHO (1991), but applied an UF of 10,000
(10 for intraspecies variation, 10 for interspecies variation, 10 for a less-than-chronic-duration
study and 10 for lack of data on carcinogenicity or chronic toxicity). No occupational exposure
limits have been established for 1,2,3-trichlorobenzene by the American Conference of
Governmental Industrial Hygienists (ACGIH, 2007), National Institute of Occupational Safety
and Health (NIOSH, 2005), or Occupational Safety and Health Administration (OSHA, 2008).
The National Toxicology Program (NTP) has not assessed the toxicity or carcinogenicity of this
compound (NTP, 2006) and it is not included in the 11th Report on Carcinogens (NTP, 2005).
1,2,3-Trichlorobenzene has not been the subject of a monograph by the International Agency for
Research on Cancer (IARC, 2008) or a toxicological profile by the Agency for Toxic Substances
Disease Registry (ATSDR, 2008).
To identify toxicological information pertinent to the derivation of provisional toxicity
values for 1,2,3-trichlorobenzene, literature searches were conducted in December 2007 using
the following databases: MEDLINE, TOXLINE, DART/ETIC, BIOSIS
(January 2000-December 2007), Current Contents (prior 6 months), TSCATS1/2, GENETOX,
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HSDB, and RTECS. Except where noted, the literature searches were not limited by date. A
toxicity review on halogenated benzenes (Leber and Bus, 2001) was also consulted for relevant
information. A final search for recently published toxicity studies was conducted for the period
from January 2008 thru March 2009.
REVIEW OF PERTINENT DATA
Human Studies
Information regarding the toxicity or carcinogenicity of 1,2,3-trichlorobenzene in humans
was not located.
Animal Studies
Oral Exposure
A subchronic toxicity study was conducted in which groups of 10 male and 10 female
weanling Sprague-Dawley rats were fed 1,2,3-trichlorobenzene (>99% pure) in dietary
concentrations of 0, 1, 10, 100, or 1000 ppm for 13 weeks (Cote et al., 1988). The diets were
prepared by blending ground feed with corn oil solutions containing appropriate amounts of
1,2,3-trichlorobenzene. Reported approximate amounts of chemical ingested in the low- to
high-dose groups were 0.08, 0.78, 7.7, and 78 mg/kg-day in the males and 0.13, 1.3, 12, and
113 mg/kg-day in the females. Endpoints evaluated throughout the study consisted of clinical
signs (daily), body weight (weekly), food consumption (5 rats/dose/sex at weeks 1, 4, 8, and 12),
and urinalysis (pH, protein, and nitrite in 5 rats/dose/sex at weeks 4, 8, and 12). Endpoints
evaluated at the end of the 13-week feeding period included hematology (hemoglobin, packed
cell volume, erythrocyte count, total and differential leukocyte counts, platelet count,
prothrombin time, mean corpuscular hemoglobin [MCH] and mean corpuscular hemoglobin
concentration [MCHC]), serum chemistry (sodium, potassium, inorganic phosphate, total
bilirubin, alkaline phosphatase [ALP], aspartate aminotransferase [AST], total protein, calcium,
cholesterol, glucose, uric acid and lactic dehydrogenase), hepatic microsomal aniline
hydroxylase and aminopyrine demethylase activities, liver protein content, and femoral bone
cytology. At necropsy, all animals were examined grossly, selected organs were weighed (liver,
kidney, spleen, heart, and brain) and comprehensive histological examinations (41 tissues) were
conducted.
Body-weight gain was 5.1, 9.8, 2.4, and 10.2% less than controls in males at 0.08, 0.78,
7.7, and 78 mg/kg-day, respectively; the decreases in the 0.78 and 78 mg/kg-day animals were
statistically (p < 0.05) significant (Cote et al., 1988). Because of the lack of clear dose-response,
the authors concluded that the effect at 0.78 mg/kg-day was probably an incidental finding.
There were no significant decreases in body-weight gain in the females or food consumption in
either sex. Relative liver weight was significantly (p < 0.05) increased in males at 78 mg/kg-day
(12.5%) higher than controls) and relative kidney weight was significantly increased in males at
0.08, 0.78, and 78 mg/kg-day (14.2, 14.2, and 21.4% higher than controls); absolute organ
weights were unchanged. The increases in kidney weight were not accompanied by renal
histopathology or abnormal urinalysis. Hematology, serum chemistry, and hepatic microsomal
enzymes were not affected by exposure. The only other exposure-related effects were
histopathological changes in the liver and thyroid. These effects were qualitatively described in
a general manner that also pertained to other trichlorobenzenes in the study. The effects were
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considered by the researchers to be generally mild in nature, biologically significant only at the
highest dose level and more severe in males than females. Hepatic changes in "most treated
groups consisted of a mild-to-moderate increase in cytoplasmic volume and anisokaryosis of
hepatocytes observed mostly in perivenous and midzone areas." High-dose rats had mild hepatic
changes "characterized by aggregated basophilia as well as widespread midzonal vacuolation
due to fatty infiltration." Thyroid changes "were characterized by reduction in follicular size,
increased epithelial height from flattened cuboidal cells to columnar shape and reduced colloid
density." The severity of the thyroid changes "varied from minimal in the low-dose groups to
mild and moderate in the high-dose groups." Other information regarding the liver and thyroid
lesions (e.g., incidence data) was not reported. Based on the mild-to-moderate histopathological
changes in the liver and thyroid of the high-dose male rats, this study identified a NOAEL of
7.7 mg/kg-day and LOAEL of 78 mg/kg-day.
A developmental toxicity study was conducted in which groups of 13-14 female
Sprague-Dawley rats were administered 1,2,3-trichlorobenzene (99.5% pure) in corn oil by
gavage in doses of 0 (vehicle control), 150, 300, or 600 mg/kg-day on Gestation Days
(GDs) 6-15 (Black et al., 1988). The dams were sacrificed on GD 22. Clinical signs were
monitored throughout the study. Maternal endpoints evaluated at termination included body
weight, hematology (hemoglobin concentration, hematocrit value, erythrocyte count, total and
differential leukocyte counts, mean corpuscular volume [MCV], MCH and MCHC), serum
chemistry (sodium, potassium, inorganic phosphorus, total bilirubin, ALP, AST, total protein,
calcium, cholesterol, glucose, uric acid and lactic dehydrogenase), hepatic microsomal aniline
hydroxylase and aminopyrine-N-demethylase activities, liver protein concentration, organ
weights (liver, kidney, spleen, heart and brain), and histopathology (25 tissues). Developmental
endpoints included resorptions and dead fetuses, litter size, fetal body weight, gross birth defects
and skeletal (approximately two-thirds of each litter), and visceral (remaining fetuses)
malformations and variations. Effects in the maternal rats included statistically significant
(p < 0.05) increases in the weight of the liver (relative to body weight) at 600 mg/kg-day
(13.7% higher than controls, with no changes in absolute liver weight or body weight) and
hepatic microsomal aminopyrine-N-demethylase activity at 600 mg/kg-day (19.7% higher than
controls) and decreases in hemoglobin concentration at 300 and 600 mg/kg-day (5.0 and
5.8%) less than controls) and hematocrit level at 600 mg/kg-day (10.5% less than controls). The
authors concluded that the changes in hemoglobin concentration and hematocrit indicated a very
mild anemia. Other maternal effects included histopathological changes in the liver and thyroid.
These effects were qualitatively described in a general manner that also pertained to other
trichlorobenzenes in the study. The hepatic changes were mild, consisted largely of increased
periportal cytoplasmic eosinophilia and mild anisokaryosis of hepatocellular nuclei and
apparently occurred at >300 mg/kg-day. The thyroid changes were mild and consisted of
reduced follicle size (often accompanied by angular collapse) at >300 mg/kg-day and increased
epithelial height and cytoplasmic vacuolation at 600 mg/kg-day. Other information regarding
the liver and thyroid lesions (e.g., incidence data) was not reported. There were no indications of
1,2,3-trichlorobenzene-induced developmental toxicity. Based on decreased hemoglobin
concentration and histopathological changes in the liver and thyroid, this study identified a
NOAEL of 150 mg/kg-day and LOAEL of 300 mg/kg-day for maternal toxicity. A NOAEL of
600 mg/kg-day and no LOAEL were identified for developmental toxicity.
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Additional toxicity studies (unpublished) may be among the Toxic Substances Control
Act (TSCA) confidential submissions that are noted in the TSCATS Low Detail Report
(U.S. EPA, 2008b) but they could not be obtained in a reasonable period of time.
Inhalation Exposure
No pertinent inhalation studies were located.
Other Studies
Gavage administration of 1,2,3-trichlorobenzene in liquid paraffin to rats at a dose level
of 780 mg/kg-day for 7 days induced nonnecrotic liver cell degeneration in the central, midzonal,
and periportal regions, as well as increases in hepatic uroporphyrin, urinary coproporphyrin, and
urinary porphobilinogen levels (Rimington and Ziegler, 1963).
A limited amount of information is available on the genotoxicity of
1,2,3-trichlorobenzene. 1,2,3-Trichlorobenzene did not induce reverse mutations in Salmonella
typhimurium TA98, TA100, TA1535, or TA1537 (Haworth et al., 1983; Nohmi et al., 1985) or
DNA repairing genes (umuDC) in S. typhimurium TA1535/pSK1002 (Ono et al., 1992), when
tested with or without metabolic activation. 1,2,3-Trichlorobenzene did not induce chromosome
aberrations in cultured Chinese hamster lung fibroblast cells when tested with or without
metabolic activation (Sofuni et al., 1985). In vivo, intraperitoneal administration of
1,2,3-trichlorobenzene to male NMRI mice caused a dose-related increase in micronucleus
formation in bone marrow polychromatic erythrocytes (Mohtashamipur et al., 1987). In this
study, two doses of 125, 250, 375, or 500 mg/kg were injected 24 hours apart and evaluations
were performed on bone marrow samples taken 30 hours after the first injection. Total doses
(i.e., 250, 500, 750, and 1000 mg/kg) ranged from 18-72% of the single dose intraperitoneal
LD50 (13 90 mg/kg).
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
ORAL RfD VALUES FOR 1,2,3-TRICHLOROBENZENE
Information relevant to oral RfD derivation is available from one subchronic toxicity
study and one developmental toxicity study. In this subchronic toxicity study, Cote et al. (1988),
exposed male and female rats to 1,2,3-trichlorobenzene (0.0, 0.08, 0.78, 7.7, and 78 mg/kg-day
in males; 0.0, 0.13, 1.3, 12, and 113 mg/kg-day in females) in the diet for 13 weeks. The main
effects included a statistically significant (p < 0.05) reduction in male rat body weight gain as
well as mild-to-moderate histopathological changes in the liver (aggregated basophilia and
widespread midzonal vacuolation due to fatty infiltration) and thyroid (reduced follicular size
and colloid density and increased epithelial height) in the high-dose animals. The study authors
noted that the observed effects were generally more severe in males than females. Based on the
body weight, liver effects, and thyroid effects in the male rat, this study identified a NOAEL of
7.7 mg/kg-day and LOAEL of 78 mg/kg-day for subchronic oral toxicity. In the developmental
toxicity study (Black et al., 1988), female rats were exposed to 150, 300, or 600 mg/kg-day of
1,2,3-trichlorobenzene by gavage on GDs 6-15. Effects in the dams included decreased
hemoglobin concentration and histopathological changes in the liver and thyroid; based on these
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effects, this study identifies aNOAEL of 150 mg/kg-day and LOAEL of 300 mg/kg-day for
maternal toxicity. No fetotoxic or teratogenic effects were observed, indicating that a NOAEL of
600 mg/kg-day and no LOAEL were identified for developmental toxicity.
Subchronic p-RfD
The NOAEL of 7.7 mg/kg-day for a reduction in male body weight gain, as well as liver
and thyroid histopathology in rats exposed to 1,2,3-trichlorobenzene for 13 weeks (Cote et al.,
1988), is used to derive the subchronic p-RfD. Benchmark dose (BMD) analysis is precluded
because the incidence of lesions was not reported. Derivation of the subchronic p-RfD involves
dividing the NOAEL by a UF of 1000. The subchronic p-RfD is calculated as follows:
Subchronic p-RfD = NOAEL UF
= 7.7 mg/kg-day ^ 1000
= 0.008 or 8 x 10 3 mg/kg-day
The composite UF of 1000 includes component UF factors of 10 for extrapolation from rats to
humans, 10 for human variability, and 10 for database insufficiencies, as explained below.
•	A 10-fold UF is applied to account for laboratory animal-to-human interspecies
differences because no information is available on the toxicity of 1,2,3-trichlorobenzene
in humans. No other information is available to assess possible differences between
animals and humans in pharmacokinetic and pharmacodynamic responses to
1,2,3-trichlorobenzene.
•	A 10-fold UF for intraspecies differences is applied to account for potentially susceptible
human subpopulations. In the absence of information on the variability in response of
humans to 1,2,3-trichlorobenzene, the full value of 10 is used.
•	A 10-fold UF is applied to account for deficiencies in the available
1,2,3-trichlorobenzene database. The oral database is limited to one subchronic
(13-week) toxicity study in rats and one developmental toxicity study in fetal rats where
no effects were observed. These studies have reporting insufficiencies and testing in only
one species. The database additionally lacks studies on reproductive toxicity,
neurotoxicity, immunotoxicity and studies with a second species.
A UF for extrapolating from a subchronic- to a chronic-duration exposure is not applied
because the POD is based upon a subchronic-duration exposure to 1,2,3-trichlorobenzene. Also
a UF for extrapolating from a LOAEL to a NOAEL is not applied because a NOAEL is
identified as the POD in the critical study.
The overall confidence in this RfD assessment is medium-to-low. Confidence in the
principal study is medium. The principal study examined relevant systemic toxicity endpoints in
rats of both sexes exposed to four dose levels and identifies a NOAEL and LOAEL, but it is
limited by qualitative and generalized reporting of critical results. Confidence in the database is
low, as discussed above. Reflecting the medium confidence in the principal study and low
confidence in the database, confidence in the subchronic p-RfD is low.
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Chronic p-RfD
No chronic oral toxicity study of 1,2,3-trimethylbenzene was located, indicating that the
subchronic p-RfD provides the only basis for derivation of a chronic p-RfD. A chronic p-RfD is
not derived because the application of an additional UF of 10 for extrapolation from a subchronic
duration study demonstrates a level of uncertainty that is inconsistent with U.S. EPA risk
assessment methods. However, the Appendix of this document contains a screening-level value
that may be useful in certain instances. Please see the attached Appendix for details.
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION RfC VALUES FOR 1,2,3-TRICHLOROBENZENE
No subchronic toxicity, chronic toxicity, or other relevant inhalation studies of
1,2,3-trichlorobenzene were located. RfC derivation is precluded by the lack of data.
PROVISIONAL CARCINOGENICITY ASSESSMENT
FOR 1,2,3-TRICHLOROBENZENE
There are no human or animal carcinogenicity data for 1,2,3-trichlorobenzene. A limited
amount of genotoxicity data suggest that 1,2,3-trichlorobenzene is not mutagenic, but may be
clastogenic. When tested in vitro, with or without metabolic activation, 1,2,3-trichlorobenzene
did not induce reverse mutations in S. typhimurium strains TA98, TA100, TA1535, or TA1537
(Haworth et al., 1983; Nohmi et al., 1985), DNA repairing genes (umuDC) in S. typhimurium
TA1535/pSK1002 (Ono et al., 1992) or chromosome aberrations in Chinese hamster lung
fibroblast cells (Sofuni et al., 1985). When tested in vivo by i.p. injection in mice,
1,2,3-trichlorobenzene induced micronuclei in bone marrow polychromatic erythrocytes
(Mohtashamipur et al., 1987).
In accordance with current EPA cancer guidelines (U.S. EPA, 2005), the available data
are inadequate for an assessment of human carcinogenic potential.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2007. TLVs® and
BEIs®: Threshold Limit Values for Chemical Substances and Physical Agents, Biological
Exposure Indices. ACGIH, Cincinnati, OH.
ATSDR (Agency for Toxic Substances and Disease Registry). 2008. Toxicological Profile
Information Sheet. U.S. Department of Health and Human Services, Public Health Service,
Atlanta, GA. Online, http://www.atsdr.cdc. gov/toxprofites/index.asp.
Black, W.D., V.E.O. Valli, J. A. Ruddick et al. 1988. Assessment of teratogenic potential of
1,2,3-, 1,2,4- and 1,3,5-trichlorobenzenes in rats. Bull. Environ. Contam. Toxicol. 41:719-26.
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Cote, M., I. Chu, D.C. Villeneuve et al. 1988. Trichlorobenzenes: Results of a thirteen week
feeding study in the rat. Drug Chem. Toxicol. 11:11-28.
Haworth, S., T. Lawlor, K. Mortelmans et al. 1983. Salmonella mutagenicity test results for
250 chemicals. Environ. Mutagen. 5(Suppl 1):3—142.
Health Canada. 1993. Trichlorobenzenes (Priority Substances List Assessment Report).
Government of Canada, Environment Canada, Health Canada. ISBN 0-662-21063-8. Cat. No.
En40-215/25E. Online, http://www.hc-sc.gc.ca/ewh-semt/alt formats/hecs-
sesc/pdf/pubs/contaminants/psll-lspl/trichlorobenzenes/tri chlorobenzenes-ene.pdf.
IARC (International Agency for Research on Cancer). 2008. Search IARC Monographs.
Online, www.cie.iarc.fr.
Leber, A.P. and J.S. Bus. 2001. Halogenated benzenes. In: Patty's Toxicology, 5th ed., Vol. 5,
E. Bingham, B. Cohrssen, and C.H. Powell, Ed. John Wiley and Sons, Inc., New York,
p. 449-504.
Mohtashamipur, E., R. Triebel, H. Straeter et al. 1987. The bone marrow clastogenecity of eight
halogenated benzenes in male NMRI mice. Mutagenesis. 2:111-113.
Nohmi, T., R. Miyata, K. Yoshikawa et al. 1985. Mutagenicity tests on organic chemical
contaminants in city water and related compounds. I. Bacterial mutagenicity tests. Eisei
Shikensho Hokoku. 103:60-64.
NTP (National Toxicology Program). 2005. 11th Report on carcinogens. U.S. Department of
Health and Human Services, Public Health Service, National Institutes of Health, Research
Triangle Park, NC. Online, http://ntp.niehs.nih.eov/ntp/roc/tocl 1 .htm.
NTP (National Toxicology Program). 2006. Management Status Report. Online.
http://ntp.ni ehs.nih.gov/?obi ectid=96A77AlC-123F-7908-7BA79AB04E206892.
NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to
Chemical Hazards. Index by CASRN. Online, http://www.cdc.eov/niosh/npe/.
Ono, Y., I. Somiya and T. Kawaguchi. 1992. Genotoxic evaluation on aromatic organochlorine
compounds by using uitiu test. Wat. Sci. Tech. 26:61-69.
OSHA (Occupational Safety and Health Administration). 2008. OSHA Standard 1915.1000 for
Air Contaminants. Part Z, Toxic and Hazardous Substances. Online.
https://www.osha.gov/pls/oshaweb/owadisp.show document?p table STANDARDS&p id=999
2.
Rimington, C. and G. Ziegler. 1963. Experimental porphyria in rats induced by chlorinated
benzenes. Biochem. Pharmacol. 12:1387-1397.
Sofuni, T., M. Hayashi, A. Matsuoka, M. Sawada, M. Hatanaka and M. Ishidate. 1985.
Mutagenicity tests on organic chemical contaminants in city water and related compounds. II.
Chromosome aberration tests in cultured mammalian cells. Eisei Shikenjo Hokoku. 103:64-75.
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U.S. EPA. 1985. Health Assessment Document for Chlorinated Benzenes. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Air Quality Planning and Standards, Washington, DC.
EPA/600/8-84/015F.
U.S. EPA. 1988. Drinking Water Criteria Document for Trichlorobenzenes. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Drinking Water, Washington, DC. August.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables (HEAST). FY-1997 Update.
Prepared by the Office of Research and Development, National Center for Environmental
Assessment, Cincinnati, OH, for the Office of Emergency and Remedial Response, Washington,
DC. July. EPA/540/R-97/036. NTIS PB 97-921199.
U.S. EPA. 2005. Guidelines for Carcinogen Risk Assessment and Supplemental Guidance for
Assessing Susceptibility from Early-Life Exposure to Carcinogens. Risk Assessment Forum,
Washington, DC. EPA/630/P-03/001F. Online.
http://www.epa.gov/raf/publications/pdfs/childrens supplement finat.pdf.
U.S. EPA. 2006. 2006 Edition Drinking Water Standards and Health Advisories. Office of
Water, Washington, DC. Summer 2006. Online.
http://water.epa.gov/drink/standards/hascience.cfm.
U.S. EPA. 2009a. Integrated Risk Information System (IRIS). Online. Office of Research and
Development, National Center for Environmental Assessment, Washington, DC.
http ://www. epa. gov/iris/.
U.S. EPA. 2008b. TSCATS Low Detail Report for 1,2,3-trichlorobenzene. Office of Pollution
Prevention and Toxics, Washington, DC.
WHO (World Health Organization). 1991. Environmental Health Criteria for Chlorinated
Benzenes other than Hexachlorobenzene. Geneva, Switzerland. Vol.128. Online.
http://www.inchem.org/documents/ehc/ehc/ehcl28.htm.
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APPENDIX. DERIVATION OF A SCREENING VALUE
FOR 1,2,3-TRICHLOROBENZENE
For reasons noted in the main PPRTV document, it is inappropriate to derive provisional
toxicity values for 1,2,3-trichlorobenzene. However, information is available for this chemical,
which, although insufficient to support derivation of a provisional toxicity value, under current
guidelines, may be of limited use to risk assessors. In such cases, the Superfund Health Risk
Technical Support Center summarizes available information in an Appendix and develops a
"screening value." Appendices receive the same level of internal and external scientific peer
review as the PPRTV documents to ensure their appropriateness within the limitations detailed in
the document. Users of screening toxicity values in an appendix to a PPRTV assessment should
understand that there is considerably more uncertainty associated with the derivation of an
appendix screening toxicity value than for a value presented in the body of the assessment.
Questions or concerns about the appropriate use of screening values should be directed to the
Superfund Health Risk Technical Support Center.
Screening Chronic p-RfD
No chronic oral toxicity studies of 1,2,3-trichlorobenzene were located. Consequently,
the NOAEL of 7.7 mg/kg-day for a reduction in male body weight gain as well as liver and
thyroid histopathology in rats exposed to 1,2,3-trichlorobenzene for 13 weeks (Cote et al., 1988)
was used to derive the chronic oral screening value. Benchmark dose (BMD) analysis is
precluded because the incidence of lesions was unreported. Derivation of the provisional chronic
oral screening value involves dividing the NOAEL by a composite UF of 10,000. The screening
chronic p-RfD is calculated as follows:
Screening Chronic p-RfD = NOAEL UF
= 7.7 mg/kg-day ^ 10,000
= 0.0008 or 8 x 10"4 mg/kg-day
The composite UF of 10,000 includes component UF factors of 10 for extrapolation from rats to
humans, 10 for human variability, 10 for extrapolation from a subchronic study, and 10 for
database insufficiencies, as explained below.
•	A 10-fold UF is applied to account for laboratory animal-to-human interspecies
differences because no information is available on the toxicity of 1,2,3-trichlorobenzene
in humans. No other information is available to assess possible differences between
animals and humans in pharmacokinetic and pharmacodynamic responses to
1,2,3-trichlorobenzene.
•	A 10-fold UF for intraspecies differences is applied to account for potentially susceptible
human subpopulations. In the absence of information on the variability in response of
humans to 1,2,3-trichlorobenzene, the full value of 10 is used.
•	A 10-fold UF for extrapolation from a subchronic study is applied in the absence of
chronic oral toxicity studies.
•	A 10-fold UF is applied to account for deficiencies in the available
1,2,3-trichlorobenzene database. The oral database is limited to one subchronic
(13-week) toxicity study in rats and one developmental toxicity study in fetal rats where
no effects were observed. These studies have reporting insufficiencies and testing in only
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one species. The database additionally lacks studies on reproductive toxicity,
neurotoxicity, immunotoxicity and studies in a second species.
An UF for extrapolating from a LOAEL to a NOAEL is not applied because a NOAEL
was identified as the POD in the critical study.
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