United States
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EPA/690/R-11/014F
Final
3-25-2011
Provisional Peer-Reviewed Toxicity Values for
1 -Bromo-4-Ethylbenzene
(CASRN 1585-07-5)
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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AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER:
J. Phillip Kaiser, PhD
National Center for Environmental Assessment, Cincinnati, OH
DRAFT DOCUMENT PREPARED BY:
National Center for Environmental Assessment, Cincinnati, OH
This document was externally peer-reviewed under contract to:
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02421-3136
Questions regarding the contents of this document 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).

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TABLE OF CONTENTS
COMMONLY USED ABBREVIATIONS	ii
BACKGROUND	1
HISTORY	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVS	2
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER)	3
DERIVATION 01 PROVISIONAL VALUES	3
CANCER WOE DESCRIPTOR	3
MODE-OF -ACTION DISCUSSION	3
REFERENCES	4
l

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COMMONLY USED ABBREVIATIONS
BMC
benchmark concentration
BMD
benchmark dose
BMCL
benchmark concentration lower bound 95% confidence interval
BMDL
benchmark dose lower bound 95% confidence interval
HEC
human equivalent concentration
HED
human equivalent dose
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
NOAELrec
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 reference concentration (inhalation)
p-RfD
provisional reference dose (oral)
POD
point of departure
RfC
reference concentration (inhalation)
RfD
reference dose (oral)
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
WOE
weight of evidence
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PROVISIONAL PEER-REVIEWED TOXICITY VALUES
l-BROMO-4-ETHYLBENZENE (CASRN 1585-07-5)
BACKGROUND
HISTORY
On December 5, 2003, the U.S. Environmental Protection Agency'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)	EPA's Integrated Risk Information System (IRIS)
2)	Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in 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 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 EPA IRIS Program. All provisional toxicity values receive internal review by a
panel of six 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 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 EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other 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 EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
No Reference Dose (RfD), Reference Concentration (RfC), or cancer assessment for
l-bromo-4-ethylbenzene is included in the IRIS database (U.S. EPA, 2010b) or on the Drinking
Water Standards and Health Advisories List (U.S. EPA, 2009). No RfD or RfC values are
reported in the (HEAST (U.S. EPA, 201 la). The CARA list (U.S. EPA, 1994) does include a
Health and Environmental Effects Profile (HEEP) for l-bromo-4-ethylbenzene (U.S. EPA, 1994)
that declined to derive noncancer toxicity values due to inadequate noncancer data and potential
carcinogenicity of the chemical. The toxicity of l-bromo-4-ethylbenzene has not been reviewed
by the AT SDR (2010) or the World Health Organization (WHO, 2010). The CalEPA (2008,
2009a,b,c,d) has not derived toxicity values for exposure to l-bromo-4-ethylbenzene. No
occupational exposure limits for l-bromo-4-ethylbenzene have been derived by the American
Conference of Governmental Industrial Hygienists (ACGIH, 2010), the National Institute of
Occupational Safety and Health (NIOSH, 2005), or the Occupational Safety and Health
Administration (OSHA, 2010).
The HEAST (U.S. EPA, 201 la) does not report an EPA (1986) cancer
weight-of-evidence classification or an oral slope factor for l-bromo-4-ethylbenzene.
l-Bromo-4-ethylbenzene has not been evaluated under the Guidelines for Carcinogen Risk
Assessment (U.S. EPA, 2005). The International Agency for Research on Cancer (IARC, 2010)
has not reviewed the carcinogenic potential of l-bromo-4-ethylbenzene.
l-Bromo-4-ethylbenzene is not included in the 11th Report on Carcinogens (NTP, 2005).
CalEPA (2009c,d) has not prepared a quantitative estimate of carcinogenic potential for
1 -bromo-4-ethylbenzene.
Literature searches were conducted on sources published from 1900 through
February 22, 2010, for studies relevant to the derivation of provisional toxicity values for
l-bromo-4-ethylbenzene, CAS No. 1585-07-5. Searches were conducted using EPA's Health
and Environmental Research Online (HERO) evergreen database of scientific literature. HERO
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searches the following databases: AGRICOLA; American Chemical Society; BioOne; Cochrane
Library; DOE: Energy Information Administration, Information Bridge, and Energy Citations
Database; EBSCO: Academic Search Complete; GeoRef Preview; GPO: Government Printing
Office; Informaworld; IngentaConnect; J-STAGE: Japan Science & Technology; JSTOR:
Mathematics & Statistics and Life Sciences; NSCEP/NEPIS (EPA publications available through
the National Service Center for Environmental Publications [NSCEP] and National
Environmental Publications Internet Site [NEPIS] database); PubMed: MEDLINE and
CANCERLIT databases; SAGE; Science Direct; Scirus; Scitopia; SpringerLink; TOXNET
(Toxicology Data Network): ANEUPL, CCRIS, ChemlDplus, CIS, CRISP, DART, EMIC,
EPIDEM, ETICBACK, FEDRIP, GENE-TOX, HAPAB, HEEP, HMTC, HSDB, IRIS, ITER,
LactMed, Multi-Database Search, NIOSH, NTIS, PESTAB, PPBIB, RISKLINE, TRI; and
TSCATS; Virtual Health Library; Web of Science (searches Current Content database among
others); World Health Organization; and Worldwide Science. The following databases outside
of HERO were searched for risk assessment values: ACGIH, ATSDR, CalEPA, EPA IRIS, EPA
HEAST, EPA HEEP, EPA OW, EPA TSCATS/TSCATS2, NIOSH, NTP, OSHA, and RTECS.
REVIEW OF POTENTIALLY RELEVANT DATA
(CANCER AND NONCANCER)
The literature search revealed no human or animal studies of acute-, short-term-, or
chronic duration for l-bromo-4-ethylbenzene.
DERIVATION OF PROVISIONAL VALUES
Limitations in the available data preclude development of cancer and noncancer toxicity
values.
CANCER WOE DESCRIPTOR
Limitations in the available data preclude development of a weight-of-evidence
descriptor.
MODE-OF-ACTION DISCUSSION
A study by Toranzo et al. (1977) examined the toxic effects of substituted
bromobenzenes on the liver of rats. Specifically, male Holtzman rats received ip injections of a
series of ortho-substituted bromobenzes—including o-bromoethylbenzene—and were sacrificed
24 hours later at which time livers were removed. Four rats were treated with
o-bromoethylbenzene at a dose of 0.15 ml/kg (unknown purity) while six rats were received an
ip injection of sesame oil (unknown purity), representing the control group. The study authors
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determined o-bromoethylbenzene to be hepatotoxic as indicated by the presence of necrotic
lesions in the liver. The study authors suggested that the toxic liver effects of
o-bromoethylbenzene were due to its metabolism to a reactive metabolite.
An in vitro study by Gottschall et al. (1983) determined the toxicity of ortho-substituted
bromobenzenes on hepatocytes. Specifically, rat hepatocytes were incubated with various
derivatives of bromobenzenes—including o-bromoethylbenzene—for 2-4 hours at various
concentrations. o-Bromoethylbenzene was tested at concentrations of 1.5 and 2.5 millimolar. By
monitoring changes in indices of toxicity (e.g., intracellular potassium, etc), study authors
determined that o-bromoethylbenzene was the most hepatotoxic of the deritaves tested.
Gottschall et al. (1983) suggested that the observed liver toxicity was most likely due to a
reactive metabolite formed during the metabolism of o-bromoethylbenzene.
These studies (i.e., Toranzo et al. 1977 and Gottschall et al. 1983) provide information
on a possible mode of action for o-bromoethylbenzene-induced toxicity. However, these studies
cannot be used for derivation of a reference value because they do not provide repeated-dose
toxicity information.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). (2010) Threshold limit
values for chemical substances and physical agents and biological exposure indices. Cincinnati,
OH. As cited in HSDB (Hazardous Substances Data Bank). Available online at
http://toxnet.nlm.nih.eov/cei-bin/sis/htmleen7HSDB. Accessed on October 4, 2010.
ATSDR (Agency for Toxic Substances and Disease Registry). (2010) Toxicological profile
information sheet. U.S. Department of Health and Human Services, Public Health Service.
Available online at http://www.atsdr.cdc.eov/toxprofiles/index.asp. Accessed on October 4,
2010.
CalEPA (California Environmental Protection Agency). (2008) All OEHHA acute, 8-hour and
chronic reference exposure levels (chRELs) as of December 18, 2008. Office of Environmental
Health Hazard Assessment, Sacramento, CA. Available online at
http://www.oehha.ca.eov/air/allrels.html.
CalEPA (California Environmental Protection Agency). (2009a) OEHHA/ARB approved
chronic reference exposure levels and target organs. Office of Environmental Health Hazard
Assessment, Sacramento, CA. Available online at
http://www.arb.ca.eov/toxics/healthval/chronic.pdf.
CalEPA (California Environmental Protection Agency). (2009b) OEHHA Toxicity Criteria
Database. Office of Environmental Health Hazard Assessment (OEHHA), Sacramento, CA.
Available online at http://www.oehha.ca.eov/riskAChemicalDB/index.asp. Accessed on October
12, 2010.
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CalEPA (California Environmental Protection Agency). (2009c) Hot spots unit risk and cancer
potency values. Office of Environmental Health Hazard Assessment, Sacramento, CA.
Available online at http://www.oehha.ca.gov/air/hot spots/pdf/TSDlookup2002.pdf.
CalEPA (California Environmental Protection Agency). (2009d) Technical support document
for describing available cancer potency factors. Appendix I. Office of Environmental Health
Hazard Assessment, Sacramento, CA. Available online at
http://www.oehha.ca.gov/air/hot spots/pdf/Appendix%20I2002.pdf.
Gottschall DW, Wiley RA, Hanzlik RP. (1983) Toxicity of ortho-substituted bromobrenzenes
to isolated hepatocytes: comparison to in vivo results. Toxicol Appl Pharmacol. 69(l):55-65.
IARC (International Agency for Research on Cancer). (2010) Agents classified by the IARC
monographs, volumes 1-100. IARC monographs on the evaluation of carcinogenic risks to
humans. Available online at
http://monographs.iarc.fr/ENG/Classification/ClassificationsCASOrder.pdf. Accessed on
October 4, 2010.
NIOSH (National Institute for Occupational Safety and Health). (2005) NIOSH pocket guide to
chemical hazards. Index by CASRN. Available online at
http://www.cdc.gov/niosh/npg/npgdcas.html. Accessed on October 4, 2010.
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. Available online at http://ntp-server.niehs.nih.gov/index.cfm?obiectid=
32BA9724-F1F6-975E-7FCE50709CB4C932. Accessed on October 4, 2010.
OSHA (Occupational Safety and Health Administration). (2010) Air contaminants: occupational
safety and health standards for shipyard employment, subpart Z, toxic and hazardous substances.
U.S. Department of Labor, Washington, DC. OSHA Standard 1915.1000. Available online at
http://www.osha.gov/pls/oshaweb/owadisp.show document?p table=STANDARDS&p id=102
86.
Toranzo, EG; Gillesse, T; Mendenhall, M; et al. (1977) Effect of substituents on arene oxide-
mediated liver toxicity among substituted bromobenzenes. Toxicol Appl Pharmacol
40(3):415-425.
U.S. EPA (Environmental Protection Agency). (1986) Guidelines for carcinogen risk
assessment. Prepared by the Risk Assessment Forum, U.S. Environmental Protection Agency.
Washington, DC. Available online at
http://www.epa.gov/raf/publications/pdfs/CA%20GUIDELINES 1986.PDF.
U.S. EPA (Environmental Protection Agency). (1994) Chemical assessments and related
activities (CARA). Office of Health and Environmental Assessment, Washington, DC.
EPA/600/R-94/904. Available online at
http://nepis.epa. gov/Exe/ZyPURL.cgi?Dockev=6000 lG8L.txt.
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U.S. EPA (Environmental Protection Agency). (2005) Guidelines for carcinogen risk
assessment. Risk Assessment Forum, Washington, D.C.; EPA/630/P-03/001F. Federal Register
70(66): 17765-17817. Available online at
http://www.epa.gov/raf/publications/pdfs/CANCER GUIDELINES FINAL 3-25-05.PDF.
U.S. EPA (Environmental Protection Agency). (2009) 2009 Edition of the Drinking Water
Standards and Health Advisories. Office of Water, Washington, DC; EPA 822-R-06-013.
Available online at http://www.epa.gov/waterscience/drinking/standards/dwstandards2009.pdf.
Accessed on October 12, 2010.
U.S. EPA (Environmental Protection Agency). (201 la) Health Effects Assessment Summary
Tables (HEAST). 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; EPA 540-R-97-036. Available online at http://epa-heast.ornl.gov/. Accessed
on October 4, 2010.
U.S. EPA (Environmental Protection Agency). (201 lb) Integrated Risk Information System
(IRIS). Office of Research and Development, National Center for Environmental Assessment,
Washington, DC. Available online at http://www.epa.gov/iris/. Accessed on October 4, 2010.
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criteria series. Available online at http://www.who.int/ipcs/publications/ehc/en/. Accessed on
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