United States
Environmental Protection
fm Agency
EPA/690/R-04/003F
Final
11-23-2004
Provisional Peer Reviewed Toxicity Values for
/?-Bromofluorobenzene
(CASRN 460-00-4)
Derivation of Subchronic and Chronic Oral RfDs
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
i.v.	intravenous
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
1

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MTD
maximum tolerated dose
MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-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
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
11

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11-23-2004
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
p-BROMOFLUOROBENZENE (CASRN 460-00-4)
Derivation of Subchronic and Chronic Oral RfDs
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) 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 (PPRTV) 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 Integrated Risk Information System (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 two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program 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 science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions (or the EPA HQ Superfund Program) sometimes
request that a frequently used PPRTV be reassessed. 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 manuscripts conclude that a PPRTV cannot be derived
based on inadequate data.
1

-------
11-23-2004
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 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.
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 manuscript 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
An RfD for/>-bromofluorobenzene (C6H4BrF) is not listed on IRIS (U.S. EPA, 2002a),
the Drinking Water Standards and Health Advisories table (U.S. EPA, 2002b), or the HEAST
(U.S. EPA, 1997). No pertinent documents are listed in the CARA database (U.S. EPA, 1991,
1994). A Drinking Water Toxicity Profile for /;-bromof1uorobcnzcnc (U.S. EPA, 1992) did not
contain sufficient information supporting an RfD derivation. ATSDR (2002) has not published a
toxicological profile for /;-bromof1uorobcnzcnc and this chemical was not listed in the NTP
(2002) Management Status Reports. IARC (2002) and WHO (2002) have not published a review
for /;-bromofluorobcnzcnc. No information pertinent to an RfD derivation for
p-bromofluorobenzene was found in a review by Leber and Bus (2001). Literature searches of
the following databases were conducted from 1994 to September 2002 for relevant studies:
TOXLINE, MEDLINE, TSCATS, GENETOX, EMIC/EMICBACK, DART/ETICBACK,
2

-------
11-23-2004
HSDB, RTECS, CCRIS, and BIOSIS. Previous literature searches of TOXLINE (1965-1994),
TSCATS and RTECS were conducted in November 1994. An updated literature search was
conducted through April 2004 and no relevant information was found. Literature search strategy
employed for this compound was based on the CASRN and at least one common name.
REVIEW OF PERTINENT LITERATURE
Human Studies
No studies were located regarding the toxicity of/>-bromofluorobenzene in humans
following oral exposure.
Animal Studies
No studies were located regarding the toxicity of/>-bromofluorobenzene in animals
following subchronic or chronic oral exposure.
One acute oral lethality study was found (DuPont, 1985; U.S. EPA, 2002c). Groups of 10
male Sprague Dawley rats were administered 1000, 2000, 3000, or 5000 mg/kg of p-
bromofluorobenzene via gavage in corn oil and sacrificed after a 14-day observation period. The
LD50 was 2700 mg/kg (95% CI: 2200-3200 mg/kg). At non-lethal doses (specific levels not
reported), tremors, limpness, and weight loss (3-19%) were observed 1-2 days after dosing. At
lethal doses, death occurred within 3 days of dosing, preceded by tremors, absence of righting
and/or grasping reflex, limpness, ataxia, lung noise, clear ocular discharge, and body weight loss
(8-21%>). No other endpoints (including gross and histological pathology) were examined.
FEASIBILITY OF DERIVING A PROVISIONAL SUBCHRONIC OR CHRONIC RfD
FOR p-BROMOFLUOROBENZENE
The lack of chronic or subchronic oral toxicity data for humans or animals precludes
derivation of a subchronic or chronic p-RfD for /;-bromofluorobcnzcne.
REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 2002. Toxicological Profile
Information Sheet. Online, http://www.atsdr.cdc.gov/toxpro2.html
3

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11-23-2004
DuPont De Nemours & Co. 1985. Median lethal dose toxicity study with INY-1059-1 in rats.
Haskell Laboratory. U.S. EPA/OTS Public Files, 8ECP submission. FicheNo. OTS0540497.
IARC (International Agency for Research on Cancer). 2002. IARC Agents and Summary
Evaluations. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
Leber, A.P. and J.S. Bus. 2001. Halogenated Benzenes. In: Patty's Toxicology. 5th ed. E.
Bingham, B. Cohrssen and C.H. Powel, Ed. John Wiley and Sons, New York. 5: 499.
NTP (National Toxicology Program). 2002. Management Status Report. Online.
http://ntp-server.niehs.nih.gov/
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1992. Drinking Water Toxicity Profiles. Office of Science and Technology, Office
of Water, Washington, DC. September.
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. 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 97-921199.
U.S. EPA. 2002a. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http://www.epa.gov/iris/
U.S. EPA. 2002b. 2002 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. EPA 822-R-02-038. Online.
http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf
U.S. EPA. 2002c. TSCATS (Toxic Substance Control Act Testing Submission database).
Online, http://www.svrres.com/esc/tscats.htm
WHO (World Health Organization). 2002. Online Catalogs for the Environmental Criteria
Series. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
4

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11-23-2004
Provisional Peer Reviewed Toxicity Values for
/?-Bromofluorobenzene
(CASRN 460-00-4)
Derivation of Subchronic and Chronic Inhalation RfCs
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
i.v.	intravenous
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
1

-------
MTD
maximum tolerated dose
MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-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
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
11

-------
11-23-2004
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
p-BROMOFLUOROBENZENE (CASRN 460-00-4)
Derivation of Subchronic and Chronic Inhalation RfCs
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) 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 (PPRTV) 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 Integrated Risk Information System (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 two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program 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 science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions (or the EPA HQ Superfund Program) sometimes
request that a frequently used PPRTV be reassessed. 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 manuscripts conclude that a PPRTV cannot be derived
based on inadequate data.
1

-------
11-23-2004
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 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.
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 manuscript 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
An RfC for /;-bromofluorobcnzcne (C6H4BrF) is not listed on IRIS (U.S. EPA, 2002) or
in the HEAST (U.S. EPA, 1997). No documents for this chemical were listed in the CARA
database (U.S. EPA, 1991, 1994). ATSDR (2002) has not published a toxicological profile for
/;-bromof1uorobcnzcnc and this chemical was not listed in the NTP (2002) Management Status
Reports. ACGIH (2002), NIOSH (2002) and OSHA (2002a,b) have not established occupational
exposure limits for />bromofluorobcnzcnc. IARC (2002) and WHO (2002) have not published
relevant reviews. No information pertinent to an RfC derivation for /;-bromof1uorobcnzcnc was
found in a review by Leber and Bus (2001). Literature searches of the following databases were
conducted from 1994 to September 2002 for relevant studies: TOXLINE, MEDLINE, TSCATS,
GENETOX, EMIC/EMICBACK, DART/ETICBACK, HSDB, RTECS, CCRIS, and BIOSIS.
Previous literature searches of TOXLINE (1965-1994), TSCATS and RTECS were conducted in
2

-------
11-23-2004
November 1994. An updated literature search was conducted through April 2004 and no relevant
information was found. Literature search strategy employed for this compound was based on the
CASRN and at least one common name.
REVIEW OF PERTINENT LITERATURE
Human Studies
No studies were located regarding the toxicity of/>-bromofluorobenzene in humans
following inhalation exposure.
Animal Studies
No studies were located regarding the toxicity of/>-bromofluorobenzene in animals
following subchronic or chronic inhalation exposure.
Two acute inhalation studies were found (DuPont, 1985; Rhone-Poulenc, 1987; U.S.
EPA, 2002b). Groups of 10 male Sprague-Dawley rats were exposed to 7.1, 14, 19, 22, or 26
mg/L air of/?-bromofluorobenzene for 4 hours and sacrificed after a 14-day observation period
(DuPont, 1985). The LC50 was 18 mg/L (95% CI: 15-21 mg/L). Exposure to 14 mg/L or greater
resulted in loss of righting reflex, diminished startle response, lethargy, tremors, spasms, labored
or rapid breathing, red nasal discharge, and darkened eyes. A slight-to-moderate body weight
loss (up to 8%) was observed in rats exposed to 7.1 mg/L and a slight-to-severe weight loss (4.1-
17.5%) was observed in the rats exposed to 14 mg/L or greater. No other endpoints (including
gross and histopathology) were examined. The second study was conducted at a lower
concentration. Groups of 10 albino Wistar rats (5/sex/group) were exposed (whole-body as
opposed to nose only) to 0 (clear air control) or 5.95 mg/L of /;-b ro m o fl uo rob c n zene for 4 hours
(Rhone-Poulenc, 1987). There were no deaths during the study. Clinical signs during exposure
were consistent with a mildly irritant vapor and included abnormal respiratory pattern and body
posture. During the post exposure observation period, signs included abnormal respiratory
pattern and fascicular tremors. Four of five female rats exposed to />-bromofluorobenzene
developed hair loss from the back during the observation period, compared to a single female
with hair loss from the head. Food and water consumption, body weight and relative lung weight
were unaffected by exposure to />-bromofluorobenzene. There were no macroscopic or
microscopic findings attributable to exposure to/>-bromofluorobenzene.
3

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11-23-2004
FEASIBILITY OF DERIVING A PROVISIONAL SUBCHRONIC OR CHRONIC RfC
FOR />-BROMOFLU OROBEN ZENE
The lack of chronic or subchronic inhalation toxicity data for humans or animals
precludes derivation of a subchronic or chronic p-RfC for /j-bromofluorobcnzcnc.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2002. TLVs® and
BEIs®: Threshold Limit Values for Chemical Substances and Physical Agents, Biological
Exposure Indices. Cincinnati, OH.
ATSDR (Agency for Toxic Substances and Disease Registry). 2002. Toxicological Profile
Information Sheet. Online, http://www.atsdr.cdc.gov/toxpro2.html
DuPont De Nemours & Co. 1985. Inhalation median lethal concentration toxicity study with
INY-1059-1 in rats. Haskell Laboratory. U.S. EPA/OTS Public Files, 8ECP submission. Fiche
No. OTS0540496.
IARC (International Agency for Research on Cancer). 2002. IARC Agents and Summary
Evaluations. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
Leber, A.P. and J.S. Bus. 2001. Halogenated Benzenes. In: Patty's Toxicology. 5th ed. E.
Bingham, B. Cohrssen and C.H. Powel, Ed. John Wiley and Sons, New York. 5: 499.
NIOSH (National Institute for Occupational Safety and Health). 2002. NIOSH Pocket Guide to
Chemical Hazards. Online. http://www.cdc.gOv/niosh/npg/.html
NTP (National Toxicology Program). 2002. Management Status Report. Online.
http://ntp-server.niehs.nih.gov/
OSHA (Occupational Safety and Health Administration). 2002a. OSHA Standard 1910.1000
Table Z-l. Part Z, Toxic and Hazardous Substances. Online.
http://www.osha-slc.gov/OshStd data/1910 1000 TABLE Z-l.html
OSHA (Occupational Safety and Health Administration). 2002b. OSHA Standard 1915.1000
for Air Contaminants. Part Z, Toxic and Hazardous Substances. Online.
http://www.osha-slc.gov/OshStd data/1915 1000.html
4

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11-23-2004
Rhone-Poulenc, Inc. 1987. Parabromofluorobenzene Acute Inhalation Study in Rats 4-Hour
Exposure. Neuilly s/Seine Cedex, France. January 12, 1987. U.S. EPA/OTS Public Files, 8ECP
submission. Fiche No. OTS0571350.
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. 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 97-921199.
U.S. EPA. 2002a. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http ://www. epa. gov/ iris/
U.S. EPA. 2002b. TSCATS (Toxic Substance Control Act Testing Submission database).
Online, http://www.svrres.com/esc/tscats.htm
WHO (World Health Organization). 2002. Online Catalogs for the Environmental Criteria
Series. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
5

-------
11-23-2004
Provisional Peer Reviewed Toxicity Values for
/?-Bromofluorobenzene
(CASRN 460-00-4)
Derivation of a Carcinogenicity Assessment
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
i.v.	intravenous
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
1

-------
MTD
maximum tolerated dose
MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-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
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
11

-------
11-23-2004
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
p-BROMOFLUOROBENZENE (CASRN 460-00-4)
Derivation of a Carcinogenicity Assessment
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) 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 (PPRTV) 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 Integrated Risk Information System (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 two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program 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 science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions (or the EPA HQ Superfund Program) sometimes
request that a frequently used PPRTV be reassessed. 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 manuscripts conclude that a PPRTV cannot be derived
based on inadequate data.
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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 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.
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 manuscript 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
A carcinogenicity assessment for /;-bromof1uorobcnzcnc (C6H4BrF) is not listed on IRIS
(U.S. EPA, 2002a), the Drinking Water Standards and Health Advisories table (U.S. EPA,
2002b), or the HEAST (U.S. EPA, 1997). No documents for this chemical are listed in the
CARA database (U.S. EPA, 1991, 1994). A Drinking Water Toxicity Profile forp-
bromofluorobenzene (U.S. EPA, 1992) contained no relevant information. ATSDR (2002) has
not published a toxicological profile for /;-bromofluorobcnzcne and this chemical was not listed
in the NTP (2002) Management Status Reports. ACGIH (2002), IARC (2002) and WHO (2002)
have not assessed the carcinogenicity of />bromofluorobcnzcnc. No information pertinent to a
carcinogenicity assessment for /j-bromofluorobcnzcnc was found in a review by Leber and Bus
(2001). Literature searches of the following databases were conducted from 1994 to September
2002 for relevant studies: TOXLINE, MEDLINE, TSCATS, GENETOX, EMIC/EMICBACK,
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DART/ETICBACK, HSDB, RTECS, CCRIS, and BIOSIS. Previous literature searches of
TOXLINE (1965-1994), TSCATS and RTECS were conducted in November 1994. An updated
literature search was conducted through April 2004 and no relevant information was found.
Literature search strategy for this compound was based on the CASRN and at least one common
name.
REVIEW OF PERTINENT LITERATURE
Human Studies
No studies of the potential carcinogenicity of /;-bromofluorobcnzcne in humans were
located.
Animal Studies
No studies of the potential carcinogenicity of /;-bromofluorobcnzcnc in animals were
located.
Other Studies
No genetic toxicity data were located for/>-bromofluorobenzene.
PROVISIONAL WEIGHT-OF-EVIDENCE CLASSIFICATION
Under the proposed U.S. EPA (1999) guidelines, the data are inadequate for an
assessment of human carcinogenic potential.
QUANTITATIVE ESTIMATES OF CARCINOGENIC RISK
Derivation of quantitative estimates of cancer risk for />-bromofluorobenzene is precluded
by the lack of data regarding carcinogenicity of this chemical.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2002. TLVs® and
BEIs®: Threshold Limit Values for Chemical Substances and Physical Agents, Biological
Exposure Indices. Cincinnati, OH.
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ATSDR (Agency for Toxic Substances and Disease Registry). 2002. Toxicological Profile
Information Sheet. Online, http://www.atsdr.cdc.gov/toxpro2.html
I ARC (International Agency for Research on Cancer). 2002. IARC Agents and Summary
Evaluations. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
Leber, A.P. and J.S. Bus. 2001. Halogenated Benzenes. In: Patty's Toxicology. 5th ed. E.
Bingham, B. Cohrssen and C.H. Powel, Ed. John Wiley and Sons, New York. 5: 499.
NTP (National Toxicology Program). 2002. Management Status Report. Online.
http://ntp-server.niehs.nih.gov/
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1992. Drinking Water Toxicity Profiles. Office of Science and Technology, Office
of Water, Washington, DC. September.
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. 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 97-921199.
U.S. EPA. 1999. Guidelines for Carcinogen Risk Assessment. Review Draft. Risk Assessment
Forum, Washington, DC. July.
U.S. EPA. 2002a. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http://www.epa.gov/iris/
U.S. EPA. 2002b. 2002 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. EPA 822-R-02-038. Online.
http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf
WHO (World Health Organization). 2002. Online Catalogs for the Environmental Criteria
Series. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
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