United States
Environmental Protection
1=1 m m Agency
EPA/690/R-13/006F
Final
4-25-2013
Provisional Peer-Reviewed Toxicity Values for
2,2-Difluoropropane
(CASRN 420-45-1)
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
Dan D. Petersen, PhD, DABT
National Center for Environmental Assessment, Cincinnati, OH
CONTRIBUTOR
Jon Reid, PhD, DABT
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
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVs	 1
INTRODUCTION	2
DERIVATION OF PROVISIONAL REFERENCE VALUES	7
ALTERNATIVE METHODS	7
CANCER WEIGHT OF EVIDENCE (WOE) DESCRIPTOR	7
REFERENCES	7
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COMMONLY USED ABBREVIATIONS
BMC
benchmark concentration
BMCL
benchmark concentration lower bound 95% confidence interval
BMD
benchmark dose
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
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
POD
point of departure
p-OSF
provisional oral slope factor
p-RfC
provisional reference concentration (inhalation)
p-RfD
provisional reference dose (oral)
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 FOR
2,2-DIFLUOROPROPANE (CASRN 420-45-1)
BACKGROUND
A Provisional Peer-Reviewed Toxicity Value (PPRTV) is defined as a toxicity value
derived for use in the Superfund Program. PPRTVs are derived after a review of the relevant
scientific literature using established Agency guidance on human health toxicity value
derivations. All PPRTV assessments receive internal review by a standing panel of National
Center for Environment Assessment (NCEA) scientists and an independent external peer review
by three scientific experts.
The purpose of this document is to provide support for the hazard and dose-response
assessment pertaining to chronic and subchronic exposures to substances of concern, to present
the major conclusions reached in the hazard identification and derivation of the PPRTVs, and to
characterize the overall confidence in these conclusions and toxicity values. It is not intended to
be a comprehensive treatise on the chemical or toxicological nature of this substance.
The PPRTV review process provides needed toxicity values in a quick turnaround
timeframe while maintaining scientific quality. PPRTV assessments are updated approximately
on a 5-year cycle for new data or methodologies that might impact the toxicity values or
characterization of potential for adverse human health effects and are revised as appropriate. It is
important to utilize the PPRTV database flittp://hhpprtv.ornl.gov) to obtain the current
information available. When a final Integrated Risk Information System (IRIS) assessment is
made publicly available on the Internet (www.epa.eov/iris). the respective PPRTVs are removed
from the database.
DISCLAIMERS
The PPRTV document provides toxicity values and information about the adverse effects
of the chemical and the evidence on which the value is based, including the strengths and
limitations of the data. All users are advised to review the information provided in this
document to ensure that the PPRTV used is appropriate for the types of exposures and
circumstances at the site in question and the risk management decision that would be supported
by the risk assessment.
Other U.S. Environmental Protection Agency (EPA) programs or external parties who
may choose to use PPRTVs are advised that Superfund resources will not generally be used to
respond to challenges, if any, of PPRTVs used in a context outside of the Superfund program.
QUESTIONS REGARDING PPRTVS
Questions regarding the contents and appropriate use of this PPRTV assessment should
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).
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INTRODUCTION
2,2-Difluoropropane (CASRN 420-45-1) is a gas that belongs to a class of chemicals
called hydrofluorocarbons (HFCs) (British Columbia Ministry of Environment, 1999). HFCs
were introduced to replace ozone-depleting substances such as CFCs (chlorofluorocarbons)
(Blowers and Lownsbury, 2010) and are mainly used for refrigeration, air conditioning, and
insulating foams, with minor uses in other applications such as fire protection systems and
medical inhalers (Tsai, 2005). Table 1 provides physicochemical properties of
2,2-difluoropropane.
Table 1. Physicochemical Properties of 2,2-Difluoropropane (CASRN 420-45-1)3
Property (unit)
Value
Boiling point (°C)
-0.4
Melting point (°C)
-105
"3
Density (g/cm )
0.92 g/mL at 20°C
Vapor pressure (Pa at 25°C)
ND
pH (unitless)
ND
Solubility in water (g/100 mL at 25°C)
ND
Relative vapor density (air =1)
ND
Molecular weight (g/mol)
80.0765
aChemIDplus (2011); Chemspider (2011).
ND = no data.
A summary of available relevant health information for 2,2-difluoropropane from
U.S. EPA and other agencies/organizations is provided in Table 2.
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Table 2. Summary of Available Toxicity Values for 2,2-Difluoropropane
(CASRN 420-45-1)
Source/Parameter"
Value
(Applicability)
Notes
Reference
Date Accessed
Cancer
IRIS
NV
NA
U.S. EPA
(2011a)
4-25-2013
HEAST
NV
NA
U.S. EPA
(2011b)
4-25-2013
IARC
NV
NA
IARC (2011)
4-25-2013
NTP
NV
NA
NTP (2011)
4-25-2013
CalFPA
NV
NA
CalEPA (2009)
4-25-2013
Noncancer
ACGIH
NV
NA
ACGIH (2011)
4-25-2013
ATSDR
NV
NA
ATSDR (2011)
4-25-2013
CalEPA
NV
NA
CalEPA (2008,
2011)
4-25-2013
NIOSH
NV
NA
NIOSH (2007)
4-25-2013
OSHA
NV
NA
OSHA (2006)
4-25-2013
IRIS
NV
NA
U.S. EPA
(2011a)
4-25-2013
Drinking water
NV
NA
U.S. EPA
(2011c)
4-25-2013
HEAST
NV
NA
U.S. EPA
(2011b)
4-25-2013
CARA HEEP
NV
NA
U.S. EPA (1994)
4-25-2013
WHO
NV
NA
WHO (2011)
4-25-2013
aSources: Integrated Risk Information System (IRIS) database; Health Effects Assessment Summary Tables
(HEAST); International Agency for Research on Cancer (IARC); National Toxicology Program (NTP); California
Environmental Protection Agency (CalEPA); American Conference of Governmental Industrial Hygienists
(ACGIH); Agency for Toxic Substances and Disease Registry (ATSDR); National Institute for Occupational Safety
and Health (NIOSH); Occupational Safety and Health Administration (OSHA); Chemical Assessments and Related
Activities (CARA) list; Health and Environmental Effects Profile (HEEP); World Health Organization (WHO).
NA = not applicable; NV = not available.
Literature searches were conducted on sources published from 1900 through April 2013
for studies relevant to the derivation of provisional toxicity values for 2,2-difluoropropane,
CASRN (420-45-1). Searches were conducted using U.S. EPA's Health and Environmental
Research Online (HERO) database of scientific literature. HERO searches the following
databases: AGRICOLA; American Chemical Society; BioOne; Cochrane Library; DOE: Energy
Information Administration, Information Bridge, and Energy Citations Database; EBSCO:
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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 relevant
health information: ACGM, AT SDR, CalEPA, U.S. EPA IRIS, U.S. EPAHEAST, U.S. EPA
HEEP, U.S. EPA OW, U.S. EPA TSCATS/TSCATS2, NIOSH, NTP, OSHA, and RTECS.
Table 3 provides an overview of the toxicity database for 2,2-difluoropropane and
includes potentially relevant repeated short-term-, subchronic-, and chronic-duration studies.
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Table 3. Summary of Potentially Relevant Data for 2,2-Difluoropropane (CASRN 420-45-1)
Category
Number of
Male/Female,
Strain, Species,
Study Type,
Study Duration
Dosimetry3
Critical Effects
NOAEL
BMDL/
BMCL
LOAEL
Reference
Comments
Human
1. Oral
Acuteb
ND
Short-term0
ND
Long-termd
ND
Chronic6
ND
2. Inhalation
Acuteb
ND
Short-term0
ND
Long-termd
ND
Chronic0
ND
Animal
1. Oral
Subchronic
ND
Chronic
ND
Developmental
ND
Reproductive
ND
Carcinogenic
ND
2. Inhalation
Subchronic
ND
Chronic
ND
Developmental
ND
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Table 3. Summary of Potentially Relevant Data for 2,2-Difluoropropane (CASRN 420-45-1)
Category
Number of
Male/Female,
Strain, Species,
Study Type,
Study Duration
Dosimetry3
Critical Effects
NOAEL
BMDL/
BMCL
LOAEL
Reference
Comments
Reproductive
ND
Carcinogenic
ND
aDosimetry: NOAEL, BMDL/BMCL, and LOAEL values are converted to an adjusted daily dose (ADD in mg/kg-d) for oral noncancer effects and a human equivalent
concentration (HEC in mg/m3) for inhalation noncancer effects. Values are converted to a human equivalent dose (HED in mg/kg-d) for oral carcinogenic effects and a
HEC for inhalation carcinogenic effects. All long-term exposure values (4 wk and longer) are converted from a discontinuous to a continuous (weekly) exposure.
Values from animal developmental studies are not adjusted to a continuous exposure.
bAcute = exposure for <24 hr (U.S. EPA, 2002)
°Short-term = Repeated exposure for >24 hr <30 d (U.S. EPA, 2002).
dLong-term = Repeated exposure for >30 d <10% lifespan (based on 70 yr typical lifespan) (U.S. EPA, 2002).
"Chronic = Repeated exposure for >10% lifespan (U.S. EPA, 2002).
ND = no data.
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DERIVATION OF PROVISIONAL REFERENCE VALUES
As shown in Table 3, no information is available regarding repeat-dose human or animal
studies of short-term, subchronic, or chronic duration for 2,2-difluoropropane by any route of
exposure. Thus, limitations in the available data preclude development of cancer and noncancer
provisional toxicity values.
ALTERNATIVE METHODS
An attempt was made to identify potential surrogate chemicals that could be used to
predict the toxicity of 2,2-difluoropropane (details regarding searches and methods are presented
in Wang et al. [2012]). Limited information exists about the toxicity of other HFCs (Tsai, 2005;
Brock et al., 2000) that could be used as potential surrogates. Several related structural analogs
were found; the two most structurally related analogs are 1,1-difluoroethane (CASRN 75-37-6)
and difluoromethane (CASRN 75-10-5). These analogs are selected based on similarity in
chemical structure, carbon number, and most importantly, the position of fluorine atoms. Other
haloalkanes, such as 2,2-dichloropropane, exhibit significant similarity (91%). Unfortunately, no
repeat-dose toxicity information was available for any of those potential surrogates and
commonality in endpoints and/or toxic effects could not be identified. Toxicity data are also
available on other hydrofluoropropanes, such as 1,1,1,3,3-pentafluoropropane and
1,1,1,3,3,3-hexafluoropropane. However, those chemicals would likely not serve as good
surrogates for 2,2-difluoropropane due to differences in fluorine atom position, which is
expected to affect the toxicity properties of these compounds.
CANCER WEIGHT OF EVIDENCE (WOE) DESCRIPTOR
No human or suitable animal data on the carcinogenicity of 2,2-difluoropropane were
identified. U.S. EPA (201 la) has not classified the carcinogenic potential of
2,2-difluoropropane, and no other agencies have reviewed or classified the carcinogenic potential
of this chemical (IARC, 2011; NTP, 2011; CalEPA, 2009). Furthermore, no studies regarding
the genotoxicity and mutagenicity of 2,2-difluoropropane were identified. Thus, the cancer
WOE descriptor for 2,2-difluoropropane is "inadequate information to assess carcinogenic
potentiaF.
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BEIs: Based on the documentation of the threshold limit values for chemical substances and
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information sheet. U.S. Department of Health and Human Services, Public Health Service.
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684152.
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Blowers, P; Lownsbury, JM. (2010) Carbon dioxide emission implications if
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British Columbia Ministry of Environment. (1999) Environmental Management Act: Ozone
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Brock, WJ; Kelly, DP; Munley, SM; et al. (2000) Inhalation toxicity and genotoxicity of
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CalEPA (California Environmental Protection Agency). (2008) All OEHHA acute, 8-hour and
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