United States
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EPA/690/R-05/011F
Final
4-15-2005
Provisional Peer Reviewed Toxicity Values for
2-Chlorobutane
(CASRN 78-86-4)
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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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
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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
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04-15-05
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
2-CHLOROBUTANE (CASRN 78-86-4)
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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04-15-05
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
The HEAST (U.S. EPA, 1997) reports that data are inadequate for quantitative risk
assessment of 2-chlorobutane. The source document for this assessment was a HEED for
Monochlorobutanes (U.S. EPA, 1988). IRIS (U.S. EPA, 2003) does not report an RfD or RfC
for 2-chlorobutane, and lists 2-chlorobutane in carcinogenicity group D (not classifiable as to
human carcinogenicity). 2-Chlorobutane is not included in the Drinking Water Standards and
Health Advisories List (U.S. EPA, 2002). The CARA list (U.S. EPA, 1991, 1994) includes the
previously mentioned HEED, as well as a HEEP for Monochlorobutanes (U.S. EPA, 1983).
ATSDR (2003) has not published a Toxicological Profile for 2-chlorobutane, and no
Environmental Health Criteria Document is available (WHO, 2003). ACGIH (2003), NIOSH
(2003), and OSHA (2003) have not developed occupational exposure limits for 2-chlorobutane.
Neither IARC (2003) nor NTP (2003) have evaluated the carcinogenicity of 2-chlorobutane.
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04-15-05
Literature searches were conducted from 1987 through October, 2003 for studies relevant to the
derivation of provisional toxicity values for 2-chlorobutane. Databases searched included:
TOXLINE (supplemented with BIOSIS and NTIS updates), MEDLINE, TSCATS, RTECS,
CCRIS, DART, EMIC/EMICBACK, HSDB, GENETOX, and CANCERLIT. In addition, the
available reviews were tree-searched to locate other potentially relevant references.
REVIEW OF PERTINENT DATA
Human Studies
Studies examining the toxicity or carcinogenicity of 2-chlorobutane in humans were not
located.
Animal Studies
In a study designed to look only for lung tumors after short-term, high-level exposure,
Poirier et al. (1975) gave groups of 10 male and 10 female strain A/Heston mice a total of 13
intraperitoneal injections (3 injections/week) of 7, 17.5, or 35 mmol/kg (648, 1620, or 3240
mg/kg) of 2-chlorobutane in tricaprylin; the study originally intended to administer 24 injections,
but was altered due to early mortality. Untreated and tricaprylin-treated mice were used as
negative controls, and urethane-treated mice were used as positive controls. Survival of animals
in the low-, mid-, and high-dose groups was 75, 75, and 50%, respectively. In the untreated and
vehicle controls and urethane-treated group, survival was >90%. Surviving animals were
sacrificed 24 weeks after the first injection. Treatment with 2-chlorobutane resulted in a dose-
related increase in the average number of lung tumors per mouse; this increase attained statistical
significance, relative to controls, in the 35 mmol/kg (3240 mg/kg) group. Urethane-treated
animals also showed a significant increase, relative to controls, in gross lung tumor formation.
Other organs examined for abnormalities were the kidney, intestine, liver, thymus, spleen, and
salivary and endocrine glands. Additional details of the toxicity of 2-chlorobutane were not
reported.
Other Studies
2-Chlorobutane (4 |iL/dcssicator) was mutagenic in Salmonella typhimurium strain
TA100 in the absence of hepatic homogenates when tested in a dessicator (Simmon, 1981).
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DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
ORAL RfD VALUES FOR 2-CHLOROBUTANE
In the absence of subchronic or chronic data on the oral toxicity of 2-chlorobutane in
humans or animals, derivation of provisional subchronic or chronic RfD values is precluded.
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION RfC VALUES FOR 2-CHLOROBUTANE
In the absence of subchronic or chronic data on the inhalation toxicity of 2-chlorobutane
in humans or animals, derivation of provisional subchronic or chronic RfC values is precluded.
DERIVATION OF A PROVISIONAL CARCINOGENICITY ASSESSMENT
FOR 2-CHLOROBUTANE
Data on the carcinogenicity of 2-chlorobutane in humans are not available. No long-term
studies of the carcinogenicity of 2-chlorobutane in animals are available; the only available study
consisted of a short-term carcinogenesis screening assay that reported positive results, but is
insufficient for determining possible carcinogenic effects of 2-chlorobutane. Limited
genotoxicity testing also produced positive results. Under the 2005 Guidelines for Carcinogen
Risk Assessment (U.S. EPA, 2005), 2-chlorobutane has inadequate information to assess
carcinogenic potential because there is no data on the carcinogenicity of 2-chlorobutane in
humans and inadequate data in animals.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2003. Threshold Limit
Values for Chemical Substances and Physical Agents and Biological Exposure Indices. ACGIH,
Cincinnati, OH.
ATSDR (Agency for Toxic Substances and Disease Registry). 2003. Internet HazDat-
Toxicological Profile Query. Online, http://www.atsdr.cdc.gov/toxpro2.html
IARC (International Agency for Research on Cancer). 2003. Search IARC Monographs.
Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
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NIOSH (National Institute for Occupational Safety and Health). 2003. Online NIOSH Pocket
Guide to Chemical Hazards. Index by CASRN. Online.
http://www.cdc.gov/niosh/npg/npgdcas.html
NTP (National Toxicology Program). 2003. Management Status Report. Online.
http://ntp-server.niehs.nih.gov/cgi/iH Indexes/ATI, SRCH/iH ATI, SRCH Frames.html
OSHA (Occupational Safety and Health Administration). 2003. 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
Poirier, L.A., G.D. Stoner and M.B. Shimkin. 1975. Bioassay of alkyl halides and nucleotide
base analogs by pulmonary tumor response in strain A mice. Cancer Res. 35(6): 1411-1415.
Simmon, V.F. 1981. Applications of the Salmonella/microsome assay. In: Short-term Tests
Chemical Carcinogens, H. Stich and R. San, Ed. Springer-Verlag, New York. p. 120-126.
U.S. EPA. 1983. Health and Environmental Effects Profile for: Monochlorobutanes. Prepared
by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Solid Waste, Washington, DC.
U.S. EPA. 1988. Health and Environmental Effects Document for Monochlorobutanes.
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.
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 PB97-921199.
U.S. EPA. 2002. 2002 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. Summer 2002. EPA 822-R-02-038. Online.
http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf
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U.S. EPA. 2003. 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. 2005. Guidelines for Carcinogen Risk Assessment. Office of Research and
Development, National Center for Environmental Assessment, Washington, DC.
EPA/63 0/P-03/001F.
WHO (World Health Organization). 2003. Online catalogs for the Environmental Health
Criteria Series. Online, http://www.who.int/dsa/cat97/zehcl.htm
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