EXTERNAL REVIEW
DRAFT
HYDROFLUOROCARBONS
AND
HYDROCHLOROFLUOROCARBONS
INTERIM REPORT
U.S. Environmental Protection Agency
Office of Toxic Substances
Washington, DC 20460
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EXTERNAL REVIEW DRAFT
HYDROFLUOROCARBONS AND HYDROCHLOROFLUOROCARBONS
INTERIM REPORT
November 15, 1990
U.S. Environmental Protection Agency
Office of Toxic Substances
Washington, DC 20460
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I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
/ WASHINGTON, D.C. 20460
I 6 le
OFF ICE OF
PESTICIDES AND TOXIC
SUBSTANCES
Dear Reader:
The Montreal Protocol, as recently amended last June in
London, calls for a worldwide effort to phase out the use of all
fully halogenated chlorofluorocarbons (CFCs), carbon
tetrachloride, halons, and methylchloroform. In addition, the
new Clean Air Act Amendments contain similar provisions for
phasing out these substances domestically. An important key to
phasing out these substances successfully is the development of
functionally similar substitutes. An important key to the latter
process is the development of information that can be used by
chemical manufacturers, processors, equipment manufacturers,
users, and others to make near-term decisions on which
substitutes and technologies to pursue. To this end, EPA made a
commitment during the Second International Conference on CFC and
Halon Alternatives held in Washington, DC (October 1989) to
prepare interim assessments on the most promising substitute
chemicals.
The attached document represents EPA's first effort at
interim assessments of the hydrochlorofluorocarbons (HCFCs) and
hydrofluorocarbons (HFCs). As new information on these
substitutes becomes available, the assessments will be revised.
EPA is also releasing an interim assessment on aqueous and
terpene cleaners. Additional substitutes, such as non-HCFC
refrigerants and semi-aqueous cleaners, will be considered as
data become available.
The interim assessments contain available information on the
toxicity of the substitutes and on potential exposure levels
incurred by workers, consumers, and the general population from
the manufacture, formulation, and use of these chemicals.
Because many of these chemicals are not yet in commerce and are
still undergoing toxicity testing, the assessment rests on
incomplete data and, therefore, should not be interpreted as a
final judgment. Nonetheless, the results of these preliminary
analyses indicate that HCFCs and HFCs can be used in a manner
safe to workers, consumers, and the general population given
appropriate technological changes and exposure control practices.
Printed on Recycled Paper
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In reaching this conclusion, we must emphasize the interim
nature of these assessments in two respects. First, as more and
better information becomes available on the toxicity of the
alternatives and their likely exposures, a more definitive
assessment can be conducted. Second, the data used in these
analyses are, in many cases, limited and assumptions are often
based more on analogy than direct measurement. As new equipment
is developed that utilizes these chemicals and as work practices
are modified to facilitate use of the substitute chemicals and to
meet the needs of the new Clean Air Act Amendments, exposures are
likely to be reduced. We urge all companies and workers involved
with the production and use of CFC substitutes to take reasonable
efforts to ensure that exposures to these chemicals are
controlled while additional data are being developed.
We look forward to an increased level of communication with
all parties that are affected by the phaseout of CFCs and other
substances subject to the Protocol. We hope that these documents
will serve as a good starting point for this dialogue at the
Third International Conference in Baltimore, Maryland (November
27 through 29), as well as in the months ahead.
Sincerely,
(jfautoL&f
Linda J. Fisher
Assistant Administrator
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TABLE OF CONTENTS
J. .
2.
3.
4.
5.
HAZARD ASSESSMENT
2.1 SUMMARY OF TOXICITY STUDIES
2.1.1 SUMMARY OF TOXICITY STUDIES OF HCFC-22 . . .
2.1.2 SUMMARY OF TOXICITY STUDIES OF HCFC-123 . .
2.1.3 SUMMARY OF TOXICITY STUDIES OF HCFC-124 . .
2.1.4 SUMMARY OF TOXICITY STUDIES OF HCFC-141b . .
2.1.5 SUMMARY OF TOXICITY STUDIES OF HCFC-142b . .
2.1.6 SUMMARY OF TOXICITY STUDIES OF HFC-152a . .
2.1.7 SUMMARY OF TOXICITY STUDIES OF HFC-134a . .
2.1.8 SUMMARY OF TOXICITY STUDIES OF HFC-125 . . .
2.2 TOXICOLOGICAL COMPARISON WITH RELATED CHEMICALS . .
2.2.1 CHLORINATED HYDROCARBONS
2.2.2 CHLOROFLUOROCARBONS
2.2.3 HYDROFLUOROCARBONS AND
HYDROCHLOROFLUOROCARBONS
2.3 TESTING STRATEGY
2.4 DEGRADATION OF HCFCS AND HFCS
OCCUPATIONAL EXPOSURE
3.1 SURROGATE APPROACH
3.2 MODELING
3.3 DATA SOURCES
3.4 SUMMARY AND CONCLUSIONS
3.5 MANUFACTURE
3.6 FOAM BLOWING
3.6.1 RIGID PUR FOAMS
3.6.2 FLEXIBLE PUR FOAMS
3.7 COMMERCIAL REFRIGERATION
3.7.1 RETAIL FOOD STORAGE
3.7.2 COLD STORAGE WAREHOUSES (CSWs)
3.7.3 CHILLERS
3.7.4 INDUSTRIAL PROCESS REFRIGERATION
3.7.5 SERVICING
3.8 MOBILE AIR-CONDITIONING
3.8.1 MANUFACTURING
3.8.2 SERVICING
3.9 STERILANT CARRIER
3.10 ELECTRONICS AND METAL CLEANING
CONSUMER EXPOSURE
GENERAL POPULATION EXPOSURE
5.1 ENVIRONMENTAL FATE
5.2 ENVIRONMENTAL RELEASE AND EXPOSURE
5.2 UNCERTAINTIES IN RELEASE, CONCENTRATION, AND
EXPOSURE ESTIMATES
J.
11
13
13
15
17
17
20
21
22
25
25
25
26
27
28
39
36
38
41
43
44
44
49
49
51
52
53
53
53
54
54
56
56
57
58
59
62
65
65
65
67
5.3 OTHER AMBIENT RELEASES 70
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1. EXECUTIVE SUMMARY
BACKGROUND
Over the past decade, there has been heightened concern
worldwide over the slow but progressive depletion of the Earth's
stratospheric ozone layer, the shield which protects the Earth
from ultraviolet (UV-B) radiation. In the 1970s, scientists
hypothesized that chlorine from^hlorofluprocarbons (CFCs) could
destroy stratospheric ozone, thus^increasing the amount of UV-B
radiation reaching the Earth's surface. Increased UV-B radiation
can lead to increased cases of skin cancers and cataracts and has
been linked to crop, fish, and materials damage.
Bromochlorofluorocarbons (halons) also destroy stratospheric
ozone, and are believed to do so at a faster rate than CFCs.
In 1978, the United States banned the use of CFCs in non-
essential aerosols (40 CFR 762) in an effort to halt ozone
depletion. By 1982, however, the global production of CFCs had
risen, thereby negating the decrease in use that had resulted
from the 1978 aerosol ban in the U. S. and other nations. Uses
of CFCs include refrigeration, metal and electronics cleaning,
production of insulating foam, mobile air conditioning, and
sterilization.
Montreal Protocol
The increase in CFC production prompted officials in the
United Nations Environment Programme (UNEP) to develop and
promote a multilateral response to stratospheric ozone depletion.
These efforts resulted in the development of an international
agreement — the 1985 Vienna Convention To Protect the Ozone
Layer — which provided the framework for the eventual adoption
of the Montreal Protocol on Substances That Deplete the Ozone
Layer. The Montreal Protocol was signed in 1987, ratified in the
U. S. in 1988, and became effective worldwide on January 1, 1989.
To date, 64 nations, 28 of which are developing countries, have
ratified the Protocol.
The Montreal Protocol, as initially ratified, requires a
freeze in production and consumption, at 1986 levels, of the
following chemicals:
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CFC-11 Trichlorofluoromethane
CFC-12 Dichlorodifluoromethane
CFC-113 1,1,2-trichloro-l,2,2,-trifluoroethane
CFC-114 1,2-Dichlorotetrafluoroethane
CFC-115 Chloropentafluoroethane
The freeze is to be followed by a phased-in reduction to 80
percent of 1986 levels beginning in mid-1993 and 50 percent
beginning in mid-1998. The Protocol also limits the production
and consumption to 1986 levels of halons 1211, 1301, and 2402,
beginning in 1992. These reductions are to be accomplished by
allocating production and consumption allowances to firms that
produced and imported these chemicals in 1986, based on their
1986 levels of activity.
On August 12, 1988, under the authority of the Clean Air
Act, EPA promulgated regulations to implement the reductions
called for in the Montreal Protocol (53 FR 20566).
London amendments to the Montreal Protocol
Scientists measuring stratospheric ozone have concluded that
the amount of global ozone in northern hemisphere mid-latitudes
has decreased 1.7 to 3 percent from 1969 to 1986, with the lowest
levels occurring in winter. This decrease is two to three times
greater than had been predicted by atmospheric models. Several
extensive scientific investigations also produced evidence that
CFCs led to decreases in stratospheric ozone during the spring
months in the area over the Antarctic pole (sometimes called the
Antarctic ozone "hole").
Scientists believe that the naturally occurring atmospheric
concentration of chlorine is 0.7 part per billion (ppb). When
the Antarctic ozone hole was first observed in the mid 1970s, the
chlorine concentration equalled approximately 2.0 ppb; it is
currently at 3.0 ppb. EPA has concluded that levels of chlorine
and bromine in the atmosphere will continue to increase
measurably despite the reductions in CFCs required by the
Montreal Protocol. Concentrations of chlorine are predicted to
exceed 8 ppb by the year 2075.
Based on these assessments, the U.S. and other Parties to
the Montreal Protocol determined that further restrictions,
including controls on other chlorinated compounds and an eventual
phaseout of CFCs, were warranted.
In June 1990, the Parties met again in London to formally
amend the Montreal Protocol to include more stringent provisions.
Under the revised Protocol:
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o all fully halogenated CFCs and carbon tetrachloride
will be phased-out by 2000,
o halons will also be phased-out by 2000 with exemptions
for essential uses, and
o methyl chloroform will be phased-out by 2005.
^v,
In addition, the Parties issued a non-binding declaration calling
for HCFCs to be used only when other alternatives are not
feasible, with phaseout by 2020 if possible, but no later than
2040. These restrictions are based on a series of recently
completed scientific, economic, and technological assessments
prepared by the Parties to the Protocol.
Clean Air Act Amendments
In November 1990, the Clean Air Act was amended to include a
number of provisions that will eliminate the production of CFCs,
halons, carbon tetrachloride, and methyl chloroform by the turn
of the century. One key provision requires EPA to set "Lowest
Achievable Emission Levels" for CFCs in the air-conditioning and
refrigeration sectors and prohibits venting of HCFCs in these
sectors within the next two years. In addition, the new Clean
Air Act requires recycling of all refrigerants in mobile air-
conditioning within the next five years.
INTERIM REPORTS
To increase the public's knowledge of the potential CFC
replacement chemicals, EPA has been working to characterize the
human health and environmental risks associated with the major
substitutes for CFCs and halons. In late 1989, EPA released a
draft strategy document, "CFC Substitutes Human Health and
Environmental Effects Program," that outlined the Agency's
approach to this task. Several offices within EPA, primarily the
Office of Toxic Substances (OTS), the Office of Air and Radiation
(OAR), and the Office of Water (OW), were involved in the
creation of the strategy document.
A focal point of the strategy was the creation of interim
reports which should help provide the public with an early
indication of the health and environmental impacts of major
chemical alternatives to the ozone depletors. Chemicals are
selected for assessment in the interim reports based on projected
use volumes and the potential for significant increases in
exposures and releases, rather than because of specific toxicity
problems associated with the chemicals.
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The interim reports are to be based on data available at the
time of publication, rather than being comprehensive documents.
Although the data in the interim reports can be expected to
change in these fast-moving fields, EPA believes that industry
and the public should have access to the information as it
becomes available. Where data for a particular chemical are not
available, EPA relies on closely related chemicals and scientific
judgment to estimate hazard and exposure factors. EPA will
prepare future reports as new data on these chemicals become
available or as other substitutes or exposure scenarios are
identified.
This first interim report focuses on eight
hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons (HCFCs) as
substitutes for the CFCs. These chemicals are:
HCFC- 22 Chlorodifluoromethane (CAS # 75-45-6)
HCFC-123 2,2-Dichloro-l,l,l-trifluoroethane (CAS # 306-
83-2)
HCFC-124 l-Chloro-l,2,2,2-tetrafluoroethane (CAS # 2837-
89-0)
HFC -125 Pentafluoroethane (CAS f 354-33-6)
HFC -134a 1,1,1,2-Tetrafluoroethane (CAS # 811-97-2)
HCFC-141b l,l-Dichloro-l-fluoroethane (CAS # 1717-00-6)
HCFC-142b l-Chloro-l,l-difluoroethane (CAS # 75-68-3)
HFC -152a 1,1-Difluoroethane (CAS # 75-37-6)
For purposes of this report, the term "hazard" refers to the
potential for human health or environmental effects because of
the inherent toxicity of a chemical. "Exposure" addresses
potential exposures to: workers who manufacture, process, or use
HFCs/HCFCs; the general population exposed to releases from
industrial sites; and consumers of products that contain HFCs and
HCFCs.
The HFCs and HCFCs have a variety of use applications. The
major uses addressed in this document include: mobile air
conditioning, refrigeration, foam insulation, electronics and
metal cleaning, and sterilization. A separate EPA report
entitled "Aqueous and Terpene Cleaning Interim Report" presents
EPA's assessment of the aqueous and terpene cleaners as
substitutes for CFC-113 and methyl chloroform, another ozone-
depleting chemical, in metal and electronics applications.
Additional chemical and process alternatives exist for the CFCs,
methyl chloroform, halons, and other ozone-depleting substances.
These alternatives warrant a similar review, but due to time
constraints and lack of information on their use, they could not
be included in this report. EPA will broaden the scope of the
next Interim Report to include additional CFC alternatives. In
the meantime, developers and users of CFC substitutes should
consider the following:
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o In developing and using alternatives to the CFCs, care must
be taken that in solving one problem we do not create
another. Any chemical or process that takes a significant
portion of the market should be capable of being used in a
safe and environmentally acceptable manner.
o In general, when making decisions about how to replace the
ozone-depleting chemicals, EPA encourages industry to first
consider a preventive approach that will reduce overall use
of chemicals through toxics use reduction, alternative
processes, or conservation. In situations where these
options do not exist, industry should avoid replacing ozone
depletors with chemicals that possess known hazards and that
cannot be used in a safe manner. EPA also cautions industry
to be prudent in choosing any chemical for which there is a
lack of hazard information and encourages those actions
which would reduce exposure and release to the environment.
As mentioned above, this interim report is based on
information that is currently available. In all cases, EPA did
not possess a full data set in terms of hazard and exposure
information for the HFCs and HCFCs. An industry consortium known
as the Program for Alternative Fluorocarbon Toxicity Testing
(PAFT) is currently involved in conducting a series of toxicity
tests on some of the HFCs and HCFCs which will greatly increase
the amount of information on the possible health effects
associated with the chemicals. In terms of the exposure
assessment, the lack of actual data on the HFCs and HCFCs is
largely due to the fact that most of these chemicals have not
been used in commerce, and exposure measurements have not been
taken during their actual use. Where data did not exist, EPA
relied on closely related chemicals and scientific judgment,
where appropriate, to estimate the anticipated exposures and
environmental releases of the HFCs and HCFCs in the given use
scenarios. EPA will update this assessment when additional
toxicity and exposure data are available.
Despite its limitations, there are several conclusions that
can be drawn from this preliminary assessment. These findings
are summarized below. This information should be provided to
formulators, users, and the workforce handling these substitutes.
OVERALL FINDINGS OF THIS ASSESSMENT
The interim assessments evaluated the available information
on the toxicity of the substitutes, as well as the potential
exposure levels to workers, consumers, and the general population
from the manufacture, formulation, and use of these chemicals.
Because many of these chemicals are not yet produced or used and
are still undergoing toxicity testing, the assessment necessarily
rests on incomplete data and therefore, should not be interpreted
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as' a final judgment. Nonetheless, the results of these
preliminary analyses indicate that HFCs and HCFCs can be used in
a manner safe to workers, consumers, and the general population,
given appropriate technological changes and exposure control
practices in some applications.
In reaching this conclusion, we must emphasize the interim
nature of these assessments in two respects. First, as more and
better information becomes available on the toxicity of the
alternatives and their likely exposures, a more definitive
assessment can be conducted. Second, the data used in these
analyses are, in many cases, limited, and assumptions are often
based more on analogy than direct measurement. As new equipment
is developed that utilizes these chemicals, and as work practices
are modified to facilitate use of the substitute chemicals and to
meet the needs of the new Clean Air Act Amendments to control
emissions, exposures are likely to be reduced. We urge all
companies and workers involved with the production and use of CFC
substitutes to take reasonable efforts to ensure that exposures
to these chemicals are controlled while additional data are being
developed.
Following are some general conclusions regarding toxicity
and exposure for the HFCs and HCFCs.
ToKicitv
Based on existing laboratory studies, the HCFCs and HFCs, as
well as the CFCs, have generally low toxicity, with both classes
of compounds exhibiting low acute toxicity. However, compared to
the CFCs, a class of compounds generally recognized as chemically
inert and biologically inactive, the HCFCs and HFCs exhibit a
greater potential for systemic effects. In general, the
available testing indicates that observed effects, including
transient central nervous system effects, developmental and
maternal toxicity, and liver toxicity, occur only at relatively
high exposure levels in animal studies. Available
carcinogenicity studies on three of these substances do not
provide evidence of a carcinogenic potential in humans;
carcinogenicity studies are ongoing or planned for four other
compounds. Section 2 of this report discusses compound-specific
toxicity information.
Exposure
To gain perspective on the potential risks associated with
the use of the HFCs and HCFCs, the Agency conducted several
assessments to estimate exposures to the general population
(primarily ambient air releases), consumers, and workers. The
results of these preliminary analyses are summarized below by
exposure category.
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General Population
The ambient exposure analysis considered releases to all
media, but quantified the fate and transport of emissions to the
ambient air only, the predominant exposure pathway. The results
of the ambient air analysis indicate that exposure levels
resulting from the manufacture and use of the HFCs and HCFCs will
pose low exposure to the general population.
Consumer
The results of the consumer exposure analysis demonstrate
that consumer exposures are expected to be low. The Agency is
still awaiting ongoing exposure testing that is being performed
by industry to better characterize household emissions from foam
insulation, a large use that the Agency was unable to quantify at
this time. The consumer assessment will be revised once these
data become available.
t
Occupational
The Agency estimated exposures in several occupational
settings, including: chemical manufacturing; foam blowing;
commercial air conditioning and refrigeration; mobile air
conditioner manufacture and service; sterilant carrier use; and
electronic and metal cleaning. Because most of the CFC
substitutes are not currently used in these sectors, only a
limited amount of occupational exposure data were available.
Therefore, the Agency used the exposure information from existing
CFC applications and modeling techniques to predict HFC and HCFC
exposure levels. Data limitations precluded consideration of the
extent to which occupational exposures could be reduced by
equipment and technology changes that are required for use with
the CFC substitutes. Preliminary use-specific exposure results
are presented in Section 3.
The Agency recognizes the limitations inherent in the
occupational exposure analysis, in particular the reliance on
existing CFC data to predict exposures for the HCFCs and HFCs.
However, the results of this preliminary analysis can guide
future exposure studies that should be undertaken to better
understand the potential exposures and risks resulting from the
use of the HFCs and HCFCs.
Traditionally, exposures to the CFCs have been relatively
high, compared to other industrial chemicals, because of the
well-known low biological activity of these compounds. Since the
HFCs and HCFCs are more reactive biologically, exposure levels
similar to those associated with the CFCs are likely to be
inappropriate in some circumstances. The results that follow
identify industrial settings in which control strategies,
different from those currently employed, may be needed.
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The preliminary findings of the occupational exposure
analysis indicate that exposures to the HFCs or HCFCs in mobile
air conditioner manufacture and service and as a sterilant
carrier are expected to be low when taking into account the
current understanding of the toxicological characteristics of the
CFC substitutes. The proposed Clean Air Act Amendments will
require mandatory recycling in mobile air conditioner servicing
in the long term (next five years), which will further reduce
exposures.
Estimated exposures in HFC/HCFC manufacture, foam blowing,
commercial refrigeration servicing, and electrical and metal
cleaning, could be relatively higher, especially under worst-case
conditions. For industrial chillers, as an example, the modeled
results indicate significant levels of exposure—both under mid-
range and worst-case operating conditions. While there is
considerable uncertainty in these exposure estimates, the
available data suggest that changes in current workplace
practices and controls may be needed to ensure that occupational
exposures in these industrial sectors are reduced.
Available information indicates that a number of changes
already under consideration by industry could reduce exposures.
In the case of chillers, for example, the HCFCs are not "drop-in"
replacements for the existing chemicals (a simplifying assumption
made in the exposure analysis because of data limitations). As
industry develops new equipment for use with these substitutes,
the need to reduce exposures should be considered. Again, the
requirements of the anticipated Clean Air Act Amendments also
contain several requirements, such as mandatory recycling in
mobile air conditioner and commercial refrigeration servicing,
that will further reduce exposures. More information is needed
to better characterize occupational exposures, including the
effectiveness of new equipment designs, controls, and workplace
practices in reducing exposure. Information on potential
exposures, releases, exposure-limiting equipment designs, and
workplace practices should be made available to chemical users
and the workforce.
Degradation
This assessment summarizes recent data related to chemical
degradation of the CFC substitutes. The HFCs and HCFCs are
considered as acceptable substitutes for the CFCs because of
their greater reactivity and, thus, shorter environmental
lifetimes. This characteristic inevitably makes these chemicals
subject to some degradation in certain uses.
For example, preliminary laboratory data suggest that under
stress conditions, small quantities of HCFC-123 can degrade to
HCFC-133a and other halogenated compounds of toxicological
8
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concern. Research to develop better information related to
degradation under actual use conditions and the employment of
possible stabilizers, is underway and will be evaluated as it
becomes available. These data will facilitate further analysis
of any potential environmental and health impacts.
ONGOING ACTIVITIES
This interim report does not present an analysis of the
risks posed by use of specific CFC substitutes. However, it does
provide an initial indication of situations in which exposures—
if maintained at levels similar to those observed with the CFCs—
could be inappropriate. These results highlight where additional
information and control strategies, different from those
currently employed, could be needed.
The Agency is awaiting the receipt of additional exposure
and toxicity data that can be used for risk characterization
purposes. One of the largest activities underway is the conduct
of new toxicity testing. This program, known as the Program for
Alternate Fluorocarbon Toxicity Testing (PAFT), was initiated
voluntarily by the CFC producers worldwide to enhance the
toxicity database on the substitutes. EPA has begun to receive
preliminary results from PAFT; the completion of other tests will
occur over the next two to three years. Table 2-3 identifies the
specific testing agreement and the schedule for completion of
these tests.
Once new exposure and toxicity data are received, EPA will
refine the information contained in this document. The Agency
will continue to address numerous issues, especially those
related to the interpretation and use of the toxicity testing
results for risk characterization purposes. Key issues will
include the relevance of the effects seen in animals to humans
and the appropriate methodologies for extrapolating from animal
studies to human exposures. In anticipation of this work,
submission of new data and comments on the information contained
in this document will be of great value.
OUTLINE OF THIS REPORT
Section 2, Hazard Assessment, presents a summary of EPA's
hazard assessment for the eight HFCs/HCFCs. The term "hazard"
refers to the potential for human health or environmental effects
because of the inherent toxicity of a chemical.
Section 3, Occupational Exposure, examines the processes by
which the HFCs and HCFCs are produced and used, and estimates
potential occupational exposures of workers through inhalation
during manufacture and use of the HFCs and HCFCs.
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Section 4, Consumer Exposure, presents EPA's estimates of
the likely exposure to consumers from use of products containing
HFCs and HCFCs.
Section 5, General Population Exposure, presents EPA's
estimates of likely industrial releases of the HFCs and HCFCs
into the environment and discusses exposure to the general
population from these releases.
More complete assessments of the human health and
ecotoxicity effects of the HFCs and HCFCs can be found in EPA's
support documents. A list of these support documents and other
references can be found at the end of this report. Additional
copies of this document and the EPA support documents can be
obtained through:
TSCA Assistance Information Service
U.S. Environmental Protection Agency
Office of Toxic Substances (TS-799)
Washington, D.C. 20460
Telephone: (202) 554-1404
FAX: (202) 554-5603
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2. HAZARD ASSESSMENT
This section discusses the health hazard information
available for the eight potential CFC substitutes, identifies
data gaps where possible and discusses the Agency testing
strategy for this class of chemicals. Because of the physical
properties and uses of these chemicals, the main route of human
exposure is through inhalation.
It should be noted that this section only assesses the
hazard information and does not provide an analysis of risks
posed by use of specific CFC substitutes. "Hazard" is defined in
this report as the intrinsic toxicity of a substance. "Risk" is
the probability that a substance will produce harmful effects
under specified conditions under which it is used. Depending on
the conditions under which it is used, a toxic substance may pose
lower risk than a relatively nontoxic one.
In general, toxicity studies are designed to dose at levels
that induce some effects. As a result, it is rare for such
toxicity testing to show no effects at all. Thus, interpretation
of toxicity testing results must take into account the nature of
the effects observed and the doses at which they occurred. In
the case of the HFCs and HCFCs, testing was performed at dosage
levels that ranged from 300 ppm to 700,000 ppm, representing a
fraction of the total air volume ranging from 0.03 percent to 70
percent. Most of the dosage levels used for testing the HFCs and
HCFCs are very high relative to other chemicals that have been
tested.
Section 2.1 presents a synopsis of currently available
hazard information on five HCFCs (HCFC-22, HCFC-123, HCFC-124,
HCFC-141b, and HCFC-142b) and three HFCs (HFC-152a, HFC-134a, and
HFC-125). A comprehensive review of available data can be found
in the hazard assessment support document. To develop an
understanding of the similarities and differences of the hazards
of the HCFCs and HFCs compared to the currently used CFCs, a
brief review of the toxicological profiles of the major CFCs is
provided in Section 2.2.
Since there is virtually no available health hazard
information of the HCFCs and HFCs in humans, the hazard
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evaluation is based mainly on animal toxicity data. There is
very limited information available on the pharmacokinetics and
metabolism of these chemicals. By analogy to CFCs (as reviewed
by the World Health Organization, WHO, 1987), the HCFCs and HFCs
are likely to be readily absorbed by the lungs during inhalation
exposure. Most of the chemical that is absorbed is expected to
be eliminated unchanged in the expired air. Available data on
HCFC-22 and HFC-134a indicate that these chemicals are likely to
undergo very limited metabolism (0.2% and 0.05%, respectively).
Further evidence for some degree of metabolism comes from the
finding of a dose-dependent urinary excretion of fluoride in a
chronic toxicity study with HFC-152a at high exposure
concentrations (10,000 and 25,000 ppm). In addition, a
metabolite common to both HCFC-123 and halothane (2-bromo-2-
chloro-l,l,l-trifluoroethane) was found bound to rat liver
proteins following acute exposure to either HCFC-123 or
halo thane. Details of the review of the metabolism data can be
found in the hazard assessment support document.
The health endpoints discussed in section 2.1 include acute
toxicity, cardiac sensitization, neurotoxicity,
subacute/subchronic/chronic toxicity, mutagenicity, oncogenicity,
developmental and reproductive toxicity. Considerations are
given to the EPA's Risk Assessment Guidelines in the evaluation
of these various health endpoints. In a number of cases, the
information presented for some of these endpoints is preliminary
or incomplete. Additional toxicity studies are either ongoing or
being planned for some of these chemicals. Once additional
toxicity data are received, the Agency will be able to provide a
more complete assessment of the potential adverse effects of
these chemicals in humans.
A description of the testing program by the PAFT industry
consortium is provided in Section 2.3. The Agency identified
additional toxicity testing to more fully characterize the
potential neurotoxicity, reproductive toxicity and oncogenicity
for some of these chemicals. The Agency has used structure
activity relationships (SAR) analysis as a predictive tool in
identifying chemicals with toxicologic concern for additional
testing needs, rather than recommending tests for all endpoints
for all 8 chemicals. Considerations are given to the chemical
reactivity of the compound (i.e., the number of halogen
substituents, the position and the kind of halogen substituents)
as well as information available on metabolism and possible
mechanisms of action. PAFT has agreed to sponsor these
additional toxicity studies as proposed by the Agency. Tentative
dates for the availability of the results of these toxicity tests
are also provided in this section.
These chemicals are not expected to be found in water at
significant levels and therefore are not likely to pose risk to
aquatic organisms. However, information on their potential
12
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aquatic toxicity can be found in the hazard assessment support
document.
2.1 SUMMARY OF TOXICITY STUDIES
2.1.1 SUMMARY OF TOXICITY STUDIES OF HCFC-22
HCFC-22 has very low acute toxicity. Its lethal
concentration ranges from 277,000 to 300,000 ppm in mice and
rabbits (Sakata et al., 81).
Cardiac sensitization is seen in an epinephrine challenge
test with HCFC-22 in dogs at a concentration of 50,000 ppm and in
mice at 400,000 ppm. No epinephrine-induced cardiac arrhythmias
were seen in monkeys at concentrations as high as 100,000 ppm
(series of studies by Aviado, Smith, Belej, et al., 74; 75).
i
HCFC-22 has been tested in chronic inhalation toxicity
studies in rats and mice (Tinston et al., 8la; 81b). No overt
toxicity was seen in rats and mice exposed to HCFC-22 up to
50,000 ppm. In the rat study, the only reported changes were a
decrease in body weight gain in high-dose males, increased body
weight gains in females of all exposure groups (1000; 10,000; and
50,000 ppm), and increases in the weights of the liver, kidney,
adrenal, and pituitary glands in high-dose females. In the mouse
study, high-dose animals were reported to be hyperactive. No
definition of hyperactivity or scoring criteria were given. No
systemic effects were seen in rats and mice at 10,000 ppm.
Mixed results have been reported in the Salmonella/mammalian
microsomal assay (Ames assay) with HCFC-22. In one study, HCFC-
22 was mutagenic in strain TA1535 (Koops, 77a; Longstaff et al.,
84). in another Ames assay, HCFC-22 tested negative (Barsky,
76). HCFC-22 was tested in the BHK-21 cellular transformation
assay (Longstaff et al., 84). It was reported to be negative;
however, no conclusions can be drawn about its activity in this
test system since no data were reported to support this claim.
HCFC-22 did not induce mutation at the hypoxanthine-guanine-
phosphoribosyl transferase (HPRT) locus of Chinese hamster ovary
(CHO) cells (McCooey, 80). Two in vivo cytogenetic studies and
two dominant lethal assays have been conducted. HCFC-22 induces
chromosomal abnormalities in the femoral bone marrow of treated
rats (Anderson et al., 77b; Anderson and Richardson, 79a) but
does not appear to induce dominant lethality in treated male mice
(Anderson et al., 77a; Hodge et al., 79c) and rats (Lee and
Suzuki, 81), although an erratic response pattern was noted in
mice.
Although HCFC-22 induces chromosomal aberrations in femoral
bone marrow, it does not appear to induce chromosomal aberrations
in germ cells of males as evidenced by the negative dominant
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lethal studies. There is no indication that HCFC-22 induces gene
mutation in mammalian cells as evidenced by a negative CHO assay.
On the basis of the data presented, HCFC-22 in all probability
does not present a mutagenic hazard to man. No further testing
for heritable genetic effects is recommended. Results in the
cellular transformation assay do not relate to heritable
mutagenic effects and do not indicate the need for further
testing.
Available epidemiological data are inadequate to evaluate
the carcinogenicity of HCFC-22 in humans. There is limited
evidence for the carcinogenicity of HCFC-22 in laboratory
animals. HCFC-22 caused small increases in fibrosarcomas (most
of which involved the salivary glands) and Zymbal gland tumors in
male rats at a high concentration (50,000 ppm). In this study,
no tumorigenic responses were observed at lower exposure
concentrations in male rats (1000 and 10,000 ppm). Further, no
increased incidence of tumors was found in female rats and mice
of both sexes when exposed to similar concentrations (Tinston et
al., 8la; 81b). HCFC-22 was also tested in another chronic
inhalation study in rats (Haltoni et al., 82; 88). No tumors
were found at the two dose levels tested (1000 and 5000 ppm).
This study is considered to be limited because the maximum
tolerated dose (MTD) appears not to have been reached. In a
limited gavage study where animals were exposed for only one year
(Longstaff, 82; Longstaff et al., 84), HCFC-22 did not induce
tumors in rats at a dose of 300 mg/kg/day.
The potential maternal and developmental toxicity of HCFC-22
has been evaluated in four studies in rats (Culik et al., 76;
Culik and Crowe, 78; Palmer et al., 78a) and one study in rabbits
(Palmer et al., 78b). No maternal or developmental toxicity was
observed in the rabbit study at exposure concentrations up to
50,000 ppm. However, HCFC-22 was found to cause maternal
toxicity in rats as evidenced by reduced-maternal body weight
gain at the highest dose tested (50,000 ppm) in the Palmer et al.
(78a) study. In addition, non-statistically significant and non-
dose-related increases of eye abnormalities (small or missing
eyes) were found in the fetuses in three rat studies at all doses
tested (first study - 1000 and 10,000 ppm; second study - 500,
1000, and 20,000 ppm; third study - 100, 300, and 10,000 ppm).
Palmer et al., (78a) then ran a large study in which there were
more than 4000 fetuses from each exposure group. Increases in
the same eye abnormalities were seen at all dose levels tested
(100, 1000 and 50,000 ppm) but statistical significance
(p < 0.05) was achieved only at the highest concentration. This
large study did not examine fetal abnormalities other than the
effects on the eye. Some reviewers have questioned the
significance of these findings because of the magnitude of this
effect in historical controls. The Agency is not yet in
possession of the primary data on historical controls.
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Except for the dominant lethal studies cited earlier, the
potential for reproductive toxicity of HCFC-22 has not been
studied.
2.1.2 SUMMARY OF TOXICITY STUDIES OF HCFC-123
HCFC-123 has low acute toxicity. Its LC^ for acute
inhalation exposure is between 28,000 and 50,000 ppm in rats
(Hall and Moore, 75; Waritz and Clayton, 66; Coate, 76) and
Chinese hamsters (Darr, 81), and its dermal LD50 is greater than
2 g/kg in rats and rabbits (Brock, 88a; Brock, 88b). Its
approximate lethal dose in an acute oral study in rats is 9 g/kg
(Henry and Kaplan, 75).
HCFC-123 is a mild ocular irritant (Brittelli, 76a) and
produces minimal dermal irritation (Brock, 88c) as demonstrated
in skin and eye irritation studies in rabbits.
Based on the results of a dermal sensitization study in
guinea pigs (Goodman and Morrow, 75), HCFC-123 is not a dermal
sensitizer.
Cardiac sensitization as measured in an epinephrine
challenge test is seen in dogs at concentrations of 20,000 ppm
and greater (Trochiomowicz and Mullin, 73). Dogs exposed to
10,000 ppm of HCFC-123 for 5 minutes followed by a challenge dose
of epinephrine showed some increased heart beat (tachycardia) as
well as signs of central nervous system (CNS) depression, but did
not exhibit cardiac sensitization.
Signs of CNS depression are consistently seen at
concentrations of HCFC-123 of 5000 ppm and greater in acute,
short-term, and subchronic inhalation studies in rats.
HCFC-123 has been shown to cause liver toxicity in one
short-term and three subchronic studies in rats and in a single
subchronic study in dogs. Pathological changes in the liver were
found in dogs exposed to 10,000 ppm, but not in those exposed to
1000 ppm (Crowe, 78). In rats, the observed liver effects were
not consistent across the studies. Significant dose-related
increases in liver weights were reported in all subchronic
studies (Crowe, 78; Industrial Biotest Laboratory, 77c; Malley,
90) at doses ranging from 500 to 10,000 ppm and from 5000 to
20,000 ppm in a 4-week study (Kelly, 89). However, mild
pathological changes were only found in one study (Industrial
Biotest Laboratory, 77c). The preliminary results of the 12
month sacrifice from an ongoing chronic study in rats showed
liver weight changes at 5000 ppm but not at lower doses (300 and
1000 ppm). A full characterization of the potential for liver
effects will be developed following the receipt of the results of
the ongoing chronic study.
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HCFC-123 has been tested in vitro in the
Salmonella/mammalian microsomal assay (Barsky and Butterworth,
76; Callander, 89) and in vivo in the micronucleus assay (Muller
and Hofmann, 88). Both assays were negative. There is no
evidence to suggest that HCFC-123 induces either gene or
chromosomal mutations and hence no reason to suspect that it
might be a germ cell mutagen. No further testing for heritable
genetic effects is recommended.
No information on the oncogenic potential of HCFC-123 is
available. An oncogenicity/chronic toxicity study on HCFC-123 in
rats is underway. EPA has received some information from the 12-
month sacrifice as mentioned above. The terminal sacrifice will
occur in January 1991. A full report of the results is expected
in early 1993.
The maternal and developmental toxicity of HCFC-123 has been
evaluated in a range-finding and a final inhalation study in
rabbits (Bio/dynamics, 89a; 89b) and two inhalation studies in
rats (Culik and Kelly, 76; Industrial Bio-Test, 77). The final
rabbit study provides evidence of maternal toxicity following
exposure to doses as low as 500 ppm of HCFC-123 as demonstrated
by significant reductions in food consumption and body weight
gain. There was no statistically significant evidence of
developmental toxicity in the final study at doses as high as
5000 ppm. However, higher doses were used in the range-finding
study. This study showed dose-related decreases in litter size
and fetal body weight (10,000 ppm or greater).
Maternal toxicity was also reported in two rat studies. A
significant reduction in maternal weight gain was seen in the
study by Industrial Bio-Test (77) when pregnant dams were exposed
to 5000 ppm (only dose tested) of HCFC-123. In the second study
(Culik and Kelly, 76), pregnant dams exposed-to HCFC-123 at
10,000 ppm (only dose tested) showed clinical signs of anesthetic
effects. No conclusive evidence of developmental toxicity was
reported, but both rat studies are considered inadequate for
hazard assessment. This is because both studies suffer from a
number of deficiencies including the use of a single dose, a
small number of animals, and an inadequate assessment of fetal
parameters (e.g., fetal body weight, visceral examination).
Data from a 2-generation reproductive effects study on HCFC-
123 and data from developmental toxicity studies on HCFC-124, a
structurally similar compound, will be used to better define the
potential for developmental toxicity of HCFC-123.
HCFC-123 will be tested in a 2-generation reproductive
effects study.
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2.1.3 SUMMARY OF TOXICITY STUDIES OF HCFC-124
HCFC-124 has very low acute toxicity. Its LCj0 for acute
inhalation exposure in rats ranges from 230,000 to greater than
360,000 ppm (Hazleton, 76; Kelly, 90).
Cardiac sensitization was seen in an epinephrine challenge
test in dogs at concentrations of 25,000 ppm and greater (Mullin,
76). No effect was observed at 10,000 ppm.
Signs of CNS depression have been seen in acute and subacute
studies of HCFC-124 at concentrations greater than 50,000 ppm.
HCFC-124 has been shown to cause absolute and relative liver
weight changes in rats in a subchronic study (Industrial Biotest
Laboratory, 77a). In this study, liver weight changes were seen
at 1000 and 5000 ppm. i HCFC-124 is being tested in another 90-day
subchronic study in rats at 5000, 15,000, and 50,000 ppm. The
results of this study should be available for evaluation in mid
1991. The results of this study will be incorporated to more
fully evaluate the potential for liver effects of HCFC-124.
HCFC-124 tested negative in the Ames assay (Barsky, 76;
Litton Bionetics, 76) and did not induce micronuclei in an
inhalation micronucleus assay in mice (Rickard, 90). There is no
evidence to suggest that it induces either gene or chromosomal
mutations and hence no reason to suspect that it might be a germ
cell mutagen. No further testing for heritable genetic effects
is recommended.
No information on the oncogenic potential of HCFC-124 is
currently available. PAFT plans to conduct an
oncogenicity/chronic toxicity study on HCFC-124 in hamsters.
HCFC-124 has not been adequately tested for developmental
toxicity. In the only available study (Industrial Biotest
Laboratory, 77b), exposure of pregnant rats to 5000 ppm of HCFC-
124 (only dose tested) produced a significant increase in
resorptions. PAFT has scheduled developmental toxicity studies
in rats and rabbits.
HCFC-124 has not been tested for reproductive toxicity. The
results of the 2-generation reproductive effects study on HCFC-
123 will be used to evaluate the need for further assessment of
this end effect for HCFC-124.
2.1.4 SUMMARY OF TOXICITY STUDIES OF HCFC-141b
HCFC-141b has low acute toxicity in inhalation, oral, and
dermal studies. Its LC^ for inhalation exposure is
approximately 60,000 ppm (Doleba-Crowe, 77b; Hardy et al., 89a).
17
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No effects were seen in oral studies at 5000 mg/kg or in dermal
studies at 2000 mg/kg (Sarver, 88; Liggett et al., 89; Gardner,
88; Brock, 89b).
HCFC-141b is a mild to moderate eye irritant and produces
nil to minimal skin irritation (Brock, 88d; Liggett, 88a; Brock,
89a; Liggett, 88b).
In a study designed to detect epinephrine-induced cardiac
sensitization in dogs (Mullin, 77), a marked response was seen at
concentrations of 5000 to 20,000 ppm. No response was noted at
2500 ppm. In a second study (Hardy et al., 89b), epinephrine-
induced cardiac arrhythmias were induced at concentrations
ranging from 9000 to 21,000 ppm in dogs and from 3000 to 10,000
ppm in monkeys.
HCFC-141b was tested for dermal sensitization in 20 female
albino guinea pigs (Kynoch and Parcel1, 88). No evidence of
delayed contact hypersensitivity was found.
Cage-side observations of transient CNS depression (effects
occurring only during exposure) were noted at 3200 ppm and
greater in rats and 4200 ppm and greater in rabbits in
developmental toxicity studies. Because these results could be
indicative of neurotoxicity, the PAFT testing program for HCFC-
141b (and HCFC-123) will closely examine the effects of CNS
depression through more careful testing of these effects (e.g.,
functional, rather than cage-side observations).
Although exposure to 20,000 ppm of HCFC-141b in a subchronic
study in rats resulted in lower body weights, decreased food
consumption, decreased responsiveness to stimuli, and increased
levels of serum cholesterol, these effects were not accompanied
by either gross or histopathological changes (Yano et al., 89;
Landry et al., 89). Thus, the overall systemic toxicity of HCFC-
14lb appears to be low.
HCFC-141b gave mixed results in the Ames assay. It was
positive in strain TA1535 in two studies (Hodson-Walker and May,
88b; Russell, 77) and negative in one study (May, 89). No
explanation for the differences in test results is available.
HCFC-l4lb does not induce chromosomal aberrations in cultured
human lymphocytes (Hodson-Walker, 90b). It does, however, induce
aberrations in cultured Chinese hamster ovary (CHO) cells
(Hodson-Walker, 90a). This is in agreement with an earlier
report (Bootman et al., 88c) in which HCFC-141b was also positive
in CHO cells in culture. However, this ability to induce
chromosomal effect in vitro is not noted when HCFC-141b is tested
in vivo. HCFC-141b has been tested twice in the mouse
micronucleus assay (Bootman et al., 88a; Vlachos, 88). It was
negative in both assays. HCFC-141b was also negative in the E.
coli assay for DNA damage in bacterial cells (Hodson-Walker and
18
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Hay, 88a) and the in vitro assay for gene mutation at the H6PRT
locus in Chinese hamster V79 cells (Bootman et al., 88b).
Given the entire set of test results for HCFC-141b, it is
concluded that in spite of the positive response in CHO cells and
the mixed results in the Ames assay, HCFC-141b in all probability
does not present a mutagenic hazard to exposed individuals. The
available mutagenicity data also do not indicate a concern for
possible carcinogenicity of this compound because currently
available data indicate that genotoxicity test results do not
correlate well with rodent carcinogenicity test results for this
class of compounds.
There is no information on the carcinogenicity of HCFC-141b.
As discussed in the hazard assessment support document, SAR
analysis indicates a low oncogenicity potential for HCFC-141b.
An oncogenicity/chronic toxicity study on HCFC-141b in rats is
underway.
i i
HCFC-141b was tested for developmental toxicity in both rats
and rabbits and found to cause developmental effects only at high
dose levels. In the rat study (Hughes et al., 88), there were
clinical signs of transient CNS depression during exposure at all
dose levels (3200, 8000, and 20,000 ppm). However, the observed
transient CNS depression was accompanied by changes in body-
weight gain and food consumption only at the highest dose tested.
Although statistical analyses were not performed on maternal
parameters, dams exposed to 20,000 ppm exhibited an 8% reduction
in mean body weight and a 44% increase in water consumption.
Developmental toxicity was evident after exposure to 20,000 ppm
of HCFC-141b as demonstrated by a significant increase in
resorptions and a significant decrease in litter size and fetal
body weight. In addition, fetuses exposed to 20,000 ppm had
increased frequencies of edema, spaces between the bodywall and
the organs, subcutaneous hemorrhages, supernumerary liver lobes,
and delays in ossification of certain skeletal elements;
statistical analyses were not performed.
In the rabbit study (Hughes et al., 89), there were no
statistically significant differences in food consumption or
maternal body weight between treated and control groups at any
dose level (1400, 4200, and 12,600 ppm). There were clinical
signs of transient CNS depression during exposure at the mid- and
high dose levels. There was no evidence of developmental
toxicity at any dose level.
HCFC-141b has not yet been tested for reproductive toxicity.
PAFT is scheduled to test HCFC-141b in a 2-generation
reproductive effects study.
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2.1.5 SUMMARY OF TOXICITY STUDIES OF HCFC-142b
HCFC-142b has very low acute toxicity. Its LCj0 for 30
minutes of exposure is greater than 300,000 ppm (Lester and
Greenberg, 50).
HCFC-142b produced only mild irritation when tested in
rabbits (Brittelli, 76b).
Epinephrine-induced cardiac arrhythmias were observed in
dogs exposed to HCFC-142b at 50,000 ppm (Mullin, 69a). No
effects were noted in monkeys and mice at concentrations up to
100,000 ppm. Noise-induced cardiac sensitization (via release of
endogenous epinephrine) was reported in dogs during a 30 second
simultaneous inhalation exposure to 800,000 ppm of HCFC-142b
(Mullin, 70).
HCFC-142b has not been tested for neurotoxicity. An acute
study (Lester and Greenberg, 50) demonstrated signs of
neurotoxicity at very high concentrations (loss of postural
reflexes at 200,000 ppm; loss of righting reflex at 250,000 ppm;
loss of corneal reflex at 300,000 ppm).
The results of a subacute (Moore, 76a) and a subchronic
study (Kelly, 76) of HCFC-142b indicate low systemic toxicity.
No effects were seen at any dose level tested (high dose = 10,000
ppm in 90-day study in rats and male dogs; high dose = 20,000 ppm
in 2-week study in male rats).
Results of a chronic inhalation study (Seckar et al., 86)
support the findings of low systemic toxicity of HCFC-142b in the
subacute and subchronic studies. No treatment-related toxic
effects were noted in an inhalation study in rats at doses up to
20,000 ppm.
HCFC-142b was mutagenic in the Ames assay (Jagannath, 77;
Longstaff and McGregor, 78; Longstaff et al., 84). As discussed
in the hazard assessment support document, HCFC-142b gave a weak
positive response when tested for its ability to induce
chromosomal aberrations in the bone marrow of male rats
(Pennwalt, 80a). HCFC-142b is considered to be without effect in
a dominant lethal assay in rats (Pennwalt, 8Ob).
HCFC-142b was also tested in both the BHK-21 (Longstaff et
al., 84) and the Balb/3T3 systems (Matheson, 78). No conclusions
can be drawn about the activity of this compound in either of
these test systems although HCFC-142b was reportedly positive in
the BHK-21 system.
Although HCFC-142b was positive in the Salmonella assay and
is a weak inducer of chromosomal aberrations in femoral bone
marrow, it does not appear to induce chromosomal aberrations in
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germ cells of males as evidenced by a negative dominant lethal
study. On the basis of the data presented, there is no evidence
to suggest that HCFC-142b presents a mutagenic hazard to man. No
further testing for heritable genetic effects is recommended.
Results in cellular transformation assays do not relate to
heritable mutagenic events and do not indicate the need for
further testing.
In a two-year inhalation study in rats on HCFC-142b (Seckar
et al., 86), no statistically significant increase of tumor
incidences were reported for any dose level (highest dose tested
= 20,000 ppm). The maximum tolerated dose (MTD) might not have
been reached in this study. However, HCFC-142b is not expected
to be oncogenic because of the negative test results combined
with SAR analysis that indicates a low oncogenicity potential for
HCFC-142b.
HCFC-l42b has not been adequately evaluated for
developmental toxicity. It has only been tested in one species,
rats. The two existing studies in rats are considered limited.
No maternal toxicity was seen in these studies. In one study,
there is suggestive evidence of developmental toxicity (pre-
implantation loss) at 1,000 and 10,000 ppm (Culik and Kelly,
76b). The other study provided only suggestive evidence of
developmental toxicity when tested at 2000 and 10,000 ppm (Damske
et al., 78).
Except for the dominant lethal study cited earlier, the
potential for reproductive toxicity of HCFC-142b has not been
studied.
2.1.6 SUMMARY OF TOXICITY STUDIES OF HFC-152a
HFC-152a has very low acute toxicity. Lethal concentrations
range from 383,000 to 500,000 ppm depending on the length of
exposure (Moore, 75; Lester and Greenberg, 50; Limperos and Zapp,
51). Test animals showed lack of coordination, labored
breathing, unresponsiveness to sound, and dose-responsive
narcosis at concentratibns of 175,000 ppm and greater.
HFC-152a is a weak cardiac sensitizer. Epinephrine-induced
cardiac arrhythmias were seen at 150,000 ppm but not at 50,000
ppm in dogs (Mullin, 69b). No effect on the cardiovascular
system of monkeys and dogs was seen at concentrations up to
200,000 ppm in the absence of an epinephrine challenge dose.
Rats did have arrhythmias at concentrations of 50,000 ppm and
greater, but rats are not considered to be a good model for
evaluating the cardiotoxicity of halogenated hydrocarbons in
humans (from a series of studies by Aviado, Smith, Belej et al.,
74; 75).
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Signs of CNS depression have been noted in acute inhalation
studies in rats at high concentrations (175,000 ppm and greater)
(Moore, 75; Lester and Greenberg, 50; Linperos and Zapp, 51). In
a 2-week study (Moore, 76b), narcosis and unresponsiveness to
sound were noted at 100,000 ppm.
Results of a chronic study in rats (McAlack, 82) indicate
that HFC-152a has low systemic toxicity. At 25,000 ppm, animals
had symptoms that were indicative of a mild reversible alteration
in the renal structure of males and females and a slight
interference in renal function in females. There was also an
increased incidence of swollen ears, ocular/nasal discharge and
wet/stained perinea in both males and females, and an increased
incidence of wet/stained body and face in females. These
symptoms may be indicative of chronic low level irritation or
stress. No effects were seen at 10,000 ppm.
HFC-152a was negative when tested in the Ames assay (Koops,
77b). No conclusions can be drawn about the activity of HFC-152a
in the Drosophila melanogaster sex-linked recessive lethal (SRL)
assay (Foltz and Fuerst, 74; Garrett and Fuerst, 74) because the
available information is inadequate to draw conclusions. There
is no evidence to indicate a concern that HFC-152a may induce
heritable effects in man. No further testing for heritable
genetic effects is recommended.
HFC-152a was non-carcinogenic in a 2-year inhalation study
in rats with a high dose of 25,000 ppm (McAlack, 82).
No statistically significant evidence of maternal or
developmental toxicity was seen in a study of HFC-152a in rats
(Culik and Kelly, 80). There was a dose-related trend in the
incidence of two skeletal anomalies. Although this finding is
suggestive of developmental toxicity, it should be noted that no
statistically significant effects were seen at 50,000 ppm. HFC-
152a has not been tested in a second species.
HFC-152a has not been tested for reproductive toxicity.
2.1.7 SUMMARY OF TOXICITY STUDIES OF HFC-134a
HFC-134a has very low acute toxicity. Lethal concentrations
range from 567,000 to 750,000 ppm in rats (Silber and Kennedy,
79a; Rissolo and Zapp, 67).
The cardiac sensitization potential of HFC-134a was
evaluated in a standard epinephrine challenge test (Mullin and
Hartgrove, 79). HFC-134a is a weak cardiac sensitizer.
Epinephrine-induced cardiac arrhythmias were seen at doses of
75,000 ppm and greater in dogs. No response was noted at 50,000
ppm.
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Signs of transient CNS depression have been seen in acute
studies (Silber and Kennedy, 79a; Rissolo and Zapp, 67) and in a
developmental toxicity study (Lu and Staples, 81) at 100,000 ppm
in rats. In a 90-day inhalation study on HFC-134a (Hext, 89),
female rats exhibited decreased brain weights at 10,000 and
49,500 ppm which were not dose related (2.77 and 2.63%,
respectively). This statistically significant change was not
accompanied by either positive histopathological findings
following the usual staining of brain and peripheral nervous
system (PNS) sample tissue or by transient CNS depression. Four-
week recovery animals from the subchronic study and 12-month
sacrifice animals from an ongoing chronic study showed no similar
decrease in brain weight. Four-week recovery animals from the
subchronic study were negative for all histopathological
findings. While EPA agrees that the available histologic reports
were negative, adequate details of the evaluation were not
provided as to which brain regions were examined. EPA is
awaiting more specific information from ongoing studies to fully
evaluate the potential neurotoxicity of this compound.
In subacute studies (14 days and 28 days) in rats (Silber
and Kennedy, 79b; Riley et al., 79), the only pathological
changes noted were in the lung indicative of focal interstitial
pneumonitis after exposure to 50,000 or 100,000 ppm of HFC-134a.
Some changes in organ weights (liver, kidney, gonad) were seen in
the 28-day study at 50,000 ppm. Increased liver weight was also
seen at 10,000 ppm in males. None of the organ weight changes
were associated with altered gross or microscopic pathology.
Other than the brain weight changes noted above, little or
no systemic toxicity was observed in rats following inhalation
exposure for 13 weeks to HFC-134a (Hext, 89). Body weight and
organ weight changes and changes in urine, blood biochemistry,
and hematology parameters were observed but were not dose-related
or consistent with time.
HFC-134a was tested three times for its ability to induce
gene mutation in the Ames assay (unpublished study submitted to
EPA, 76; Taylor, 78; Callander and Priestley, 90). Results were
consistently negative. HFC-134a was also nonmutagenic when
tested in an assay for micronucleus formation in the femoral bone
marrow of treated mice (Muller and Hofmann, 89) and appears to be
negative in the dominant lethal assay (Hodge et al., 79a). The
results of the chromosomal aberrations assay are inconclusive
(Anderson and Richardson, 79b). In addition, HFC-134a did not
induce unscheduled DNA synthesis (UDS) in rat hepatocytes in vivo
(Trueman, 90). There is no evidence to suggest that HFC-134a
induces either gene or chromosomal mutations and hence no reason
to suspect that it may induce heritable effects in man. No
further testing for heritable genetic effects is recommended.
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HFC-134a did not induce tumors in a limited oral bioassay
(animals were exposed for only one year) (Longstaff et al., 84);
however, this study is inadequate to assess the oncogenic
potential of HFC-134a because of the short duration of exposure
and the use of only one dose level. SAR analysis for HFC-l34a
predicts a low potential for oncogenic activity because fluorine
generally has lower biological activity than other halogens.
PAFT is conducting a chronic inhalation study in rats.
Three inhalation studies have been conducted on the
potential maternal/developmental toxicity of HFC-134a? two were
conducted in rats (Lu and Staples, 81; Hodge et al., 79b) and one
in rabbits (Wickramaratne, 89a; 89b). One rat study with a small
sample size (n = 7 or 14) demonstrated maternal toxicity after
exposure to 100,000 ppm (reduced response to noise stimuli,
uncoordinated movements) or 300,000 ppm (significant reduction in
food consumption and body weight gain, no response to noise
stimuli, severe tremors, uncoordinated movements) of HFC-134a.
Developmental toxicity was also evident after exposure to 300,000
ppm of HFC-134a as demonstrated by a significant reduction in
fetal body weight and a significant increase in the incidence of
several skeletal variations. No statistically significant
effects were seen at 30,000 ppm. The second rat study, which
used a much larger sample size (n = 29 to 30), provided no
statistically significant evidence of maternal toxicity after
exposure to doses as high as 50,000 ppm of HFC-134a.
Developmental toxicity was evident after exposure to 50,000 ppm
as demonstrated by a significant reduction in fetal body weight
and a significant increase in the incidence of several skeletal
variations.
In the rabbit study, maternal toxicity was evident after
exposure to 10,000 ppm or more as demonstrated by a statistically
significant reduction in food consumption and body weight gain.
Developmental toxicity was also evident after exposure to 10,000
ppm or 40,000 ppm. Exposure to 10,000 ppm or more resulted in a
statistically significant dose-related increase in the fetal
incidence, but not the litter incidence, of unossified 7th lumbar
transverse processes.
There was a dose-related increase in the incidence of
gaseous distention of the stomach. Although the incidence at
40,000 ppm (12.7%) was only slightly outside the range for
historical controls (2.3 - 11.5%), the difference when evaluated
by number of fetuses was statistically significant. When
evaluated by numbers of litters, this statistical change is not
apparent. This effect was seen in 7/23, 7/18, 7/21, and 9/23
litters in the control, 1400, 4200, and 12,600 ppm groups,
respectively. Gaseous distention can be caused by gasping air.
The reason(s) for the increase is unclear but could be indicative
of non-random handling of the animals or lung problems. No
maternal or developmental effects were seen at 2500 ppm.
24
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HFC-134a has not been tested for reproductive toxicity.
Decreased gonad weights were noted in a 28-day study at the
highest dose tested (50,000 ppm) (Riley et al., 79); however, the
significance of this finding is unclear because no effect on the
gonads (either pathological or weight changes) was noted in the
subchronic study (Hext, 89) at similar dose levels.
2.1.8 SUMMARY OF TOXICITY STUDIES OF HFC-125
HFC-125 has very low acute toxicity. Its LC^ via
inhalation is reported to be 700,000 ppm (Vogelsberg, 90).
No other toxicity data on HFC-125 are available. The
potential for adverse effects from exposure to HFC-125 can be
evaluated by drawing on an analogy between HFC-125 and HFC-134a.
Details of these studies are presented in the review of HFC-134a.
2.2 TOXICOLOGICAL COMPARISON WITH RELATED CHEMICALS
A direct comparison of chlorinated hydrocarbons, CFCs and
HCFC/HFCs provides a meaningful and useful basis for evaluating
the HCFCs as a physicochemically-related class of compounds and
for developing (1) individual hazard assessments and (2) a
strategy of identifying individual toxicity testing requirements.
A detailed discussion of the toxicity of chlorinated hydrocarbons
and CFCs is beyond the scope of this report; however, some
generalization in regard to biological effects of each of these
groups of compounds can be made based on SAR analysis. In
general, effects from chlorinated hydrocarbons occur at lower
levels and are more severe than are seen with either CFCs or
HFCs/HCFCs.
2.2.1 CHLORINATED HYDROCARBONS
The short chain saturated chlorinated hydrocarbons are
important solvents and feedstocks.
Overall, this class of compounds is of low acute toxicity.
High concentrations may produce renal and hepatic dysfunction and
pulmonary irritation. Most chemicals in this class are moderate
cardiac sensitizers and are known to produce CNS depression. The
liver is often a target organ for chronic toxicity.
Depending on the degree of halogenation, stereochemical
considerations, and metabolism to genotoxic intermediates, some
compounds in this class are genotoxic, mutagenic and/or
carcinogenic. The predictive power of mutagenicity tests for
these compounds is limited.
25
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2.2.2 CHLOROFLUOROCARBONS
The following section provides a description of toxicity
data for CFC-11, CFC-12, and CFC-113. These three compounds are
the most significant chlorofluorocarbons in current use, from the
point of view of production as well as widespread use. This
class of compounds came into commercial production at a time when
toxicological testing requirements were limited by today's
standards. Thus, many of the available studies may not be
adequate to fully characterize important endpoints. However,
under the conditions of human exposure, no striking examples of
chronic toxicity have emerged. The data support a broad
comparison for a variety of toxic effects of the major CFCs with
the chlorinated hydrocarbons. In general, it can be shown that
the CFCs are less toxic.
Both CFC-11 and CFC-12 have relatively low acute toxicity
(inhalation LC50 is greater than 100,000 ppm in animals).
Alterations in both pulmonary compliance and resistance have been
observed in humans following exposure to CFC-11 and CFC-12
(Clayton, 67). In comparison to the chlorinated hydrocarbons,
the CFCs exhibit generally lower acute toxicity.
Cardiotoxicity has been studied in greatest detail with both
CFC-11 and CFC-12. Both compounds have been observed to produce
an increase in heart rate and decrease in blood pressure in
monkeys (at 50,000 ppm), arrhythmias, and increases in vagal-
heart acetylcholinesterase activity in an isolated preparation
(Young and Parker, 75; Doherty and Aviado, 75). Many of the
observed effects can be blocked by treatment with a beta-
adrenergic blocker. It was also noted that CFC-11 sensitizes
cardiac muscle to the effects of epinephrine, while CFC-12
exhibits either minor sensitization potential or no effect on
epinephrine activation of cardiac muscle. These are effects
common to halogenated hydrocarbons.
In terms of hepatotoxicity, CFC-12 has been studied in both
continuous (90-day) and repeated exposures (8h/5 days/6 weeks) at
4000 ppm in rats, monkeys, rabbits, and guinea pigs. Following
both continuous and repeated exposures at very low concentrations
(100 ppm), only the guinea pigs exhibited extensive liver damage.
However, the fact that no liver pathology was noted in any of the
other species, taken together with the authors' acknowledgement
that the guinea pig has an inherent susceptibility in continuous
exposure studies suggest that these agents, unlike the
chlorinated hydrocarbons, are not directly hepatotoxic, and that
the guinea pig response appears to be an allergic response
(Prendergast et al., 67; Maltoni et al., 88).
As reported by WHO (89), CFC-11, CFC-12 and CFC-113 have
been tested for developmental toxicity. In addition, CFC-12 and
CFC-113 were tested for reproductive effects. Although some of
26
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these studies may be limited by today's standards and thus not
all results are conclusive, none of the studies showed evidence
of reproductive or developmental toxicity. Therefore, it appears
that CFCs would have low potential for toxicity in this category.
CFC-12 has been studied for potential neurotoxicity. In
humans, motor skills were affected (20,000 ppm); in rats,
anesthetic effects were observed at 400,000 ppm (Azar et al.,
72). These findings indicate the apparent anesthetic effect that
has been observed throughout with CFCs, HFCs, and HCFCs (see
below). Epidemiological evaluation of the human exposure
experience reveals no associated neurotoxicity or behavioral
effects with chronic exposure to general anesthetics, but no
systematic testing of this endpoint has been done in animals.
With regards to carcinogenicity, chronic inhalation studies
with either CFC-ll or CFC-12 (at 5000 ppm) were conducted in both
rats and mice and reported no significant incidence of tumors
(Prendergast et al., 67; Maltoni et al., 88). This is a low
dose, not likely to be a maximum tolerated dose (MTD). Long-term
oral carcinogenicity studies of CFC-ll and CFC-12 have given
negative results (WHO, 89). CFC-113 was evaluated in a chronic
study at a well-defined MTD of 20,000 ppm and also produced no
increased tumor incidence (Wood, 85).
CFC-ll and CFC-12 are negative for mutagenicity in the Ames
assay with and without activation in TA98, TA1538, TA100, and
TA1535 strains (Longstaff et al., 84). There are no chromosomal
damage studies for these compounds. It should be noted that many
mutagenicity assays provide inconsistent data and poor
reproducibility with a variety of halogenated hydrocarbons.
2.2.3 HYDROFLDOROCARBONS AND HYDROCHLOROFLUOROCARBONS
HCFCs and HFCs share common physicochemical features, and
toxicity tests produce similar qualitative results. While actual
data gaps are apparent, extrapolation within the matrix is
possible and affords a rational basis for developing a toxicity
testing strategy. Several general observations are evident for
HCFCs and HFCs.
All appear to be of low acute toxicity and are generally
significantly less acutely toxic than either the halogenated
hydrocarbons or the CFCs. Only HCFC-123 and HCFC-141b exhibit
LC50's in the 50,000 ppm range. All others range from 100,000 to
700,000 ppm.
All HCFCs appear to be weak cardiac-sensitizers (with
epinephrine) as described for CFCs.
27
-------
Two chemicals induce some effects on the liver. Both HCFC-
123 and HCFC-124 cause liver weight changes but only HCFC-123 has
been found to cause some pathological changes at high exposure
levels (10,000 ppm in dogs). The HCFCs are, thus, similar to the
CFCs and exhibit little marked potential for frank liver
toxicity, unlike the chlorinated hydrocarbons.
Some of the HCFCs and HFCs cause maternal toxicity as
evidenced by a decrease in food consumption and body weight gain.
Developmental effects are also seen at dosages that equal or are
greater than the maternally toxic dose. A consideration of SAR
and available data for compounds such as dibromochloropropane,
halothane, and HCFC-133a suggest the reproductive system as a
potential target for HCFCs. The class of HCFCs, thus appear to
have a somewhat greater potential for reproductive and
developmental toxicity than do the CFCs.
Like the chlorinated hydrocarbons and CFCs, all HCFCs and
HFCs appear to cause CNS depression much like the general
anesthetics. At the present time, they have not been adequately
studied in animals.
There is not an abundance of carcinogenicity data on the
HFCs or HCFCs. The available carcinogenicity data on three
compounds (HCFC-22, HFC-152a, and HCFC-142b) do not provide
evidence of a significant carcinogenic potential in humans
although some studies are limited. SAR analysis suggests a low
carcinogenic potential for HFCs and some HCFCs (e.g., HCFC-141b
and HCFC-142b).
It should be noted again that many mutagenicity assays
provide inconsistent data and poor reproducibility with this
class of compounds. While the HCFCs are sometimes positive in
the Ames assay, HFCs are all negative in the Ames assays.
Because of the same technical difficulties a general comparison
with the CFCs is not easily made. No clear picture emerges from
the results of the available genotoxicity assays.
2.3 TESTING STRATEGY
After all of the currently available animal studies were
reviewed, the Agency developed a testing strategy to fill data
gaps. Instead of testing all compounds for all possible adverse
effects, analogies between individual chemicals are used to
address some toxicological endpoints.
The CFC producers initiated the Program for Alternative
Fluorocarbon Toxicity Testing (PAFT) in 1983 to develop a
comprehensive, common toxicology data base to support the
manufacture, introduction and use of alternatives by
28
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manufacturers internationally. This is the first time that an
industry, representing companies from around the world, has
voluntarily joined to evaluate the toxicology of limited
production or research chemicals. The status of the PAFT testing
program is presented in Table 2-1. Table 2-2 lists the
participating PAFT companies. The program is divided into three
parts. PAFT I is investigating and reviewing the toxicology of
HCFC-123 and HFC-134a; PAFT II, HCFC-141b; PAFT III, HCFC-124 and
HFC-125.
In designing the PAFT programs factors considered were
safety, an urgent need for toxicology information, availability
of the compounds in amounts sufficient to sustain long-term
tests, the economic future of these alternatives, and the
availability of space for inhalation studies in qualified
toxicology laboratories. Additionally, consideration was given
to the testing requirements in the United States, Europe, and the
Far East.
The program integrates past and present toxicological
information to enable an evaluation of health effects including
elements of acute, subchronic, developmental and chronic
inhalation studies, genotoxicity studies, oncogenicity studies
and environmental studies. Most of the tests in PAFT I and PAFT
II, excluding the chronic studies, have been completed and work
is underway on the PAFT III program.
PAFT studies in progress and schedules for completion are
listed in Table 2-3. Studies already submitted to the Agency are
listed in Table 2-4.
EPA evaluated the PAFT testing program and identified
additional testing needs for neurotoxicity and reproductive
toxicity, EPA also asked for a change in the oncogenicity
testing program for HCFC-123 and HCFC-124.
29
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TABLE 2-1 STATUS OF TESTING PROGRAM
HCFC-
22
"Acute
"CSens
"Neuro
8Subchr
"Muta
8Onco
"Devel
aRepro
T
T
NT
T
T
T
T
NT
HCFC-
123
T
T
P
T
T
O
*T
P
HCFC-
124
T
T
NT
O
T
P
O
NT
HCFC-
14 Ib
T
T
O
T
T
O
T
P
HCFC-
142b
T
T
NT
T
T
T
«T
NT
HFC-
152a
T
T
NT
T
T
T
"T
NT
HFC-
134a
T
T
NT
T
T
O
T
NT
HFC-
125
T
NT
NT
P
P
NT
P
NT
As discussed in Section 2.3, testing for neurotoxicity and
reproductive effects will be conducted on two compounds, HCFC-123
and HCFC-141b. The need for testing additional compounds will be
evaluated when the results of these studies are available.
T = tested for this endpoint; NT = not tested for this endpoint;
P = testing planned for this endpoint; O = testing ongoing for
this endpoint
a Acute = acute toxicity; CSens = cardiac sensitization; Neuro =
neurotoxicity; Subchr = subchronic toxicity; Muta = mutagenicity;
Onco = oncogenicity in at least one species; Devel =
developmental toxicity in two species; Repro = 2-generation
reproductive effects study
b HCFC-22 has been tested for oncogenicity in rats and mice
c tested in rats and rabbits, test results inconclusive in rats.
The results from the reproductive effects study in rats will be
used to determine the need for further testing for developmental
toxicity in rats.
d tested in one species only, test results inconclusive. The
potential for developmental toxicity for HCFC-142b can be
evaluated by comparison to that of HCFC-141b.
e tested in one species only. The potential for developmental
toxicity for HFC-152a can be evaluated by comparison to that of
HFC-134a.
30
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TABLE 2-2 PAFT COMPANIES
1. AKZO Chemical Holland
2. Allied-Signal USA
3. Asahi Glass Japan
4. ATO Chem, NA USA
5. ATO Chem, SA France
6. Central Glass Japan
7. Daikin Japan
8. Du Pont USA
9. Hoechst Germany
10. ICI England
11. Kali Chemi Germany
12. Montefluos Italy
13. Rhone-Poulenc ISC Div. France
14. Showa Denko Japan
15. Solvay & CIE Belgium
16. Ulsan Chemical Korea
Neurotoxicity testing is needed for this class of
compounds because signs of CNS depression are consistently seen
in the available studies (acute, subacute, subchronic, and
developmental toxicity studies). EPA selected HCFC-123 and HCFC-
14Ib for neurotoxicity testing because they are the most acutely
toxic of the eight compounds, and signs of CNS depression were
seen at lower exposure levels in the existing studies for these
two compounds than for the other compounds. In addition to the
effects noted in animal studies with various HCFC compounds, the
support for neurotoxicity for this class of compounds is also
based on human evidence suggesting possible impairment of psycho-
motor and cognitive performance associated with inhalation
exposure to CFC-11 (trichlorofluoromethane), CFC-12 (dichlorodi-
fluoromethane), and CFC-113 (l,2,2-trichloro-l,l,2-tri-
fluoromethane) (as reviewed by WHO, 1987).
31
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EPA considers it necessary for HCFC-123 to be tested in a
2-generation reproductive effects study. Positive findings of
reproductive effects in HCFC-133a assays, similarities evident by
SAR analysis, and suggestive results in existing developmental
toxicity studies prompt this decision. To fully characterize the
potential reproductive hazards of the class of HCFCs, EPA also
designates HCFC-141b to be tested for this effect.
As discussed in the hazard assessment support document,
SAR analysis identified HCFC-123 and HCFC-124 as having the
greatest potential for oncogenic activity. In order to account
for differences in species sensitivity, HCFC-123 and HCFC-124
will be tested for oncogenicity in different species.
Genotoxicity test results do not correlate well with rodent
carcinogenicity test results for this class of compounds.
Therefore, additional genotoxicity testing is not expected to
contribute to an understanding of the carcinogenic potential of
these compounds.
EPA will reevaluate any additional testing needs, if
necessary, based on its analysis of the entire testing package.
TABLE 2-3
PAFT STUDIES IN PROGRESS, SCHEDULED OR CURRENTLY
UNDER DEVELOPMENT AS PROVIDED BY PAFT ON 8/23/90
PAFT I
HCFC-123
Chronic Study Initiated Jan. 1989
Terminal Sacrifice Jan. 1991
Final Report 1st quarter 1993
Inhalation Reproduction Study
Tentative Start Jan. 1991
Tentative Completion
of In-Life Mar. 1991
Final Report 1st quarter 1993
Neurotoxicology Evaluation
Tentative Start Jan. 1991
Terminal Sacrifice Apr. 1991
Final Report 1st quarter 1993
HFC-l34a
Chronic Study Initiated Oct. 1989
Terminal Sacrifice Nov. 1991
Final Report 4th quarter 1993
32
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TABLE 2-3 (cont)
PAFT II
HCFC-141b
Chronic Study Initiated Jan. 1990
Terminal Sacrifice Jan. 1992
Final Report 1st quarter 1994
Inhalation Reproduction Study
Tentative Start Jan. 1991
Tentative Completion
of In-Life Mar. 1992
Final Report 1st quarter 1993
Neurotoxicology Evaluation
Initiated Jan. 1990
In-Life Completion June 1990
Final Report 1st quarter 1991
PAFT III
HCFC-124
Subchronic Inhalation
Study Initiated May 1990
In-Life Completion Aug. 1990
Final Report 2nd quarter 1991
Rat Teratology
Study Initiated May 1990
In-Life Completion Aug. 1990
Final Report 2nd quarter 1991
Rabbit Teratology
Tentative Start Jan. 1991
In-Life Completion Feb. 1991
Final Report 2nd quarter 1992
Chronic Study Dates not yet determined
HFC-125 No studies have been placed yet.
Identification of a source for the test
compound is completed. Completion of a
subchronic inhalation and two species
teratology is estimated by 4th quarter 1992.
HFC-125 will also be tested in a battery of
mutagenicity assays.
33
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TABLE 2-4 PAFT STUDIES SUBMITTED TO EPA
PAFT I
HCFC-123 An Inhalation Range-Finding study to
Evaluate the Toxicity of CFC 123 in the
Pregnant Rabbit
Primary Dermal Irritation Study with HCFC
123 in Rabbits
Acute Dermal Toxicity Study of HCFC 123 in
Rabbits
Acute Dermal Toxicity Study of HCFC 123 in
Rats
An Inhalation Developmental Toxicity Study
in Rabbits with HCFC 123
A 4-Week Inhalation Study with HCFC 123 in
Rats
HCFC 123: Ames Assay using Strains TA98,
100, 1535, 1537, 1538 with and without
Metabolic Activation
Haskell Laboratory Report "Subchronic-
Inhalation Toxicity: 90-Day Study with HCFC
123 in Rats"
HCFC 123 Micronucleus Test in Male and
Female NMRI Mice after Inhalation
HFC-134a HFC 134a - Embryotoxicity Inhalation Study
in the Rabbit
HFC 134a: Teratogenicity Inhalation Study
in the Rabbit
HFC 134a: 90-Day Inhalation Toxicity Study
in the Rat
HFC 134a - Teratogenicity Study in the Rat
(Comments only)
HFC 134a: In vivo Micronucleus Assay
Conducted by Hoechst
HFC 134a - An Evaluation Using the
Salmonella Mutagenicity Assay (CTL/P/2422)
34
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TABLE 2-4 (cont)
HFC 134a Assessment for the Induction of
Unscheduled DNA Synthesis in Rat Hepatocyte
In vivo
HFC 134a: An Evaluation in the In vivo
Cytogenetic Assay in Human Lymphocytes
PAFT II
HCFC-14lb Skin Irritation in Rabbits of HFC 14Ib
Primary Eye Irritation Study with HFC 14Ib
in Rabbits
Acute Oral Toxicity Study with HFC 14Ib in
Male Rats
Acute Dermal Toxicity Study of HFC 14Ib in
Rabbits
House Bone Marrow Micronucleus Assay of HFC
14 Ib
Irritant Effects on the Rabbit Eye of 4874-
89 (HFC 141b)
Irritant Effects on Rabbit Skin of 4874-89
(HFC 141b)
Acute Dermal Toxicity to Rats of 4874-89
(HFC 14 Ib)
HFC 14Ib: 2-Week Inhalation Toxicity Study
in the Rat
PWC 4874-789 Acute Inhalation Toxicity Study
in Rats ($-Hour Exposure)
1,1-Dichloro-l-fluoroethane: 4-Week
Inhalation Toxicity Study with Fischer 344
Rats
1,l-Dichloro-1-fluoroethane: 13-Week
Inhalation Toxicity Study with Fischer 344
Rats
Delayed contact Hypersensitivity in the
Guinea Pig with 4874-89 (HFC 141b)
35
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TABLE 2-4 (cent)
HCFC-141b - Assessment of Mutagenic
Potential in Amino-Acid Auxotrophs of
Salmonella typhimurium and £. coli including
the First Amendment
A Study of the Effect of HCFC 141b on the
Pregnancy of a Rat
A Study of the Effect of HCFC 14Ib on the
Pregnancy of the Rabbit
Acute Oral Toxicity to Rats of PWC 4874-89
Acute Inhalation Toxicity of FC141b in Rats
Acute Dermal Toxicity of FC 14Ib in Rats
Acute Oral Toxicity Studies of FC 14Ib in
Rats
HCFC 14Ib: Cardiac Sensitization in Monkeys
and Dogs
HCFC 14Ib: Final Report - Preliminary
Pharmacokinetics
Determination of Acute Toxicity of HCFC 14Ib
to Daphnia magna
Determination of Acute Toxicity of HCFC 14Ib
to Brachydanio rerio
Exposure of Cultured Human Lymphocytes to
Vapors of HCFC 14Ib
Effects of HCFC 14Ib on Chromosome of
Culture Chinese Hamster Ovary Cells
2.4 DEGRADATION OF HCFCS AND HFCS
The HCFCs and HFCs are considered as acceptable
substitutes for the CFCs because of their greater reactivity and,
thus, shorter environmental lifetimes. This characteristic would
tent to make these chemicals subject to some degradation in
certain uses. Industry has provided EPA with the results of a
review of published and unpublished information on the
decomposition of HCFCs and HFCs. This information suggests that
36
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HCFC-123 can decompose to HCFC-133a depending on such factors as
temperature, the presence of metals, the presence of organic
materials (such as oil), and pH. other halogenated hydrocarbons,
including halogenated butenes, were also reported.
A variety of toxicity studies of HCFC-133a were run in the
1970s (see hazard assessment support document, Appendix A).
HCFC-133a was found to be toxic and industry dropped their
interest in the compound as a commercial product. HCFC-133a was
carcinogenic in a rat study where 300 mg/kg/day was administered
orally for one year (Longstaff et al., 84). Animals were held
until week 125 and then examined. HCFC-133a has also been tested
in a series of dominant lethal assays in mice (Hodge et al., 79d;
80; Kilmartin et al., 80). HCFC-133a caused reduced fertility
and sperm abnormalities at 100 ppm and greater.
There are great uncertainties regarding the levels of
HCFC-133a that would form under actual conditions of use and
storage. Most of the currently available data were generated
under stress conditions. Industry has provided EPA with
screening test results designed to examine the compatibility of
HCFC-123 with various materials present in large refrigeration
systems, rigid foams, and solvent applications. Some of these
conditions probably exceed those that would be encountered in
practice, and, in general, it was under these conditions that the
highest levels of HCFC-133a were found as breakdown products.
Research to develop better information related to
degradation under actual use conditions and the employment of
possible stabilizers, is underway and will be evaluated as it
becomes available. In particular, tests are being conducted to
determine the extent to which decomposition products form over
longer periods of time during use. The potential for adverse
health effects from exposure to HCFC-133a and other decomposition
products will be evaluated when potential exposures are
characterized.
37
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3. OCCUPATIONAL EXPOSURE
This section characterizes potential occupational
exposures resulting from routine use of the eight HFCs and HCFCs.
Potential exposures resulting from accidental releases of
HFC/HCFCs are not addressed in this document. Although numerous
other chemicals and/or alternative technologies having the
potential for replacing CFCs have been identified, an assessment
of these alternatives is beyond the scope of this document. The
information presented in this report is contained in a draft
document titled, "Occupational Exposure and Environmental Release
Data for Chloroflourocarbons (CFCs) and their Substitutes. (PEI,
1990) .
The following occupational exposure scenarios are
addressed in this section: manufacture, foam blowing,
refrigeration, mobile air-conditioning, sterilant carrier, and
metal and electronics cleaning. As can be seen from Table 3-1,
these scenarios correspond to uses that account for the great
majority of CFC consumption. Table 3-2 provides a summary of
potential uses for the eight HFCs and HCFCs as described in
recent United Nations Environment Programme (UNEP) documents.
Occupational exposure assessments require information on:
the populations exposed; worker activities leading to exposure;
routes of exposure; and the frequency, duration, and levels of
exposure. Providing there is a complete and representative set
of information, a comprehensive exposure assessment would relate
worker activities to exposures and present the range and the
distribution of monitoring data. In the case of the above HFCs
and HCFCs (except for manufacturing and to a limited extent for
certain foam blowing operations) there were no personal
monitoring data available to characterize potential exposures,
primarily because these chemicals are not currently in
significant commercial use.
38
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TABLE 3-1 EXISTING CFC U.S. CONSUMPTION SUMMARY, 1985
USE
Foam blowing
Refrigeration (1)
Mobile air
conditioning
Sterilant
carrier
Electronics and
Metal Cleaning
Aerosol Use
TOTAL
CFC consumption, million kilograms
CFC-11
68
8
None
None
None
4
80
CFC-12
16
47
44
22
None
8
137
CFC-113
None
None
None
None
69
Unknown
69
CFC-114
3.5
0.5
None
None
None
Unknown
4.0
CFC-115
None
5
None
None
None
None
5
Source:
Note:
EPA, 89a
(1) Refrigeration includes both commercial refrigeration
and air conditioning
39
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TABLE 3-2 LIKELY HCFC AND HFC SUBSTITUTES FOR CFG USES
USE
Foam
blowing
Refriger-
ation (1)
Mobile air
conditioning
Sterilant
carrier
Electronics
Metal Clean
HCFC22
X
X
X
HCFC123
X
X
X
X
HCFC124
X
X
X
X
HFCJ.25
X
HFC134a
X
X
HCFC141b
X
X
X
X
HCFC142b
X
X
X
HFC1523
X
X
An "X" indicates the HCFC or HFC may possibly be a CFC substitute for the use
noted. A blank space indicates no information was found indicating that this HCFC or HFC
may be a CFC substitute for the use noted.
Sources: UNEP, 89a; UNEP, 89b; UNEP, 89c; UNEP, 89d.
Note:
(1) Refrigeration includes both commercial refrigeration
and air conditioning
-------
Two techniques were used to estimate the range of possible
exposure levels: a surrogate approach, based on existing CFC
personal inhalation monitoring data, and modeling. For each of
these analytical approaches, both mid-range and outerbound
occupational exposures were estimated based on available
information, including information on the existing CFCs. Mid-
range exposures are presented to provide a sense of what likely
or average exposures may potentially be. The Agency has a high
degree of confidence that potential exposures are likely to be
less than the outerbound level presented; there is more
uncertainty in the estimates of the mid-range values. The two
techniques used to estimate exposure are discussed below,
followed by a summary of key data sources used in these analyses.
3.1 SURROGATE APPROACH
Data on the existing CFCs offer some promise as surrogate
information to assess potential exposures to the substitutes
because of the similarities in their use patterns as well as
their physical/chemical properties relative to the HFCs and
HCFCs. Some physical and chemical properties of the HFCs and
HCFCs are presented in Table 3-3.
The use of existing CFC exposure data as a surrogate
method for quantifying exposures to the HFCs/HCFCs has several
important limitations that must be noted:
o First, only a limited amount of data was found on the
existing CFCs and it may not be representative of typical
workplace exposures. A significant proportion of the data
was collected by NIOSH in response to complaints.
Therefore, there may be some biases associated with this
data.
o Second, since the HFCs and HCFCs will not be "drop-in"
substitutes in most cases, industry will need to design
new equipment. The higher cost of the substitutes and
anticipated State and Federal regulations, such as the
Amendments to the Clean Air Act, will move industry
towards developing new equipment that will minimize
releases of HFC/HCFCs to the workplace and the
environment. Because EPA does not possess actual data
which show the effect of potential technological changes
on the actual workplace exposures, reductions could not be
quantified in the surrogate approach.
o Third, the exposures to the substitutes, (particularly the
outerbound exposures) may effectively be reduced if
threshold limit values (TLVs) or other recommended or
required exposure limits are established which are below
those currently in place for the existing CFCs.
41
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TABLE 3-3 SELECTED PHYSICAL CHARACTERISTICS OF THE HFCs/HCFCs
Characteristics
HCFC-22
HCFC-123
HCFC-124
HFC-125
Formula
Appearance
Odor
Physical State
Molecular Weight
CHC1F2
colorless
ethereal
gas
87
Vapor Pressure, nonHg 10,995
Boiling Point, "C
Water Solubility"
-40.8
0.300
CF3CHC12
colorless
ethereal
liquid
153
688
27.9
0.39
CF3CHC1F
colorless
odorless
gas
137
3155
-10.2
1.71
CF3CHF2
colorless
ethereal
gas
120
9309b
-48.5
0.094
TABLE 4-3 continued
Characteristics
HFC-134a HCFC-141b
HCFC-142b
HFC-152a
Formula
Appearance
Odor
Physical State
Molecular Weight 102
Vapor Pressure, mmHg 4965
Boiling Point, *C -26.5
Water Solubility" 0.15
CF3CH2F CC12FCH3
colorless colorless
ethereal ethereal
gas liquid
117
517
32.0
0.5b
CHF2CH3
CC1F2CH3
colorless colorless
ethereal faint
gas
101
2260
-9.8
0.5
gas
66
4018
-25.8
1.7
8 Water solubility in lb/100 Ib 1^0 at 25'C.
b Estimated by a duPont representative.
Source: Modified from PEI, 1990.
42
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3.2 MODELING
The modeling technique used in this assessment has been
used in the past by EPA to develop risk management decisions.
The model chosen uses a mass balance approach coupled with
assumptions regarding the size and duration of releases, room
size, and the extent of ventilation to estimate worker exposures
in enclosed spaces. Engineering judgment was used to estimate
typical ranges and distributions of possible values of the model
input variables. A Monte Carlo selection technique was used to
calculate corresponding distributions of potential exposures.
In this analysis, modeling was used to estimate potential
worker inhalation exposures to CFC substitutes during manufacture
and servicing of commercial refrigeration and air conditioning
systems and also during the charging and servicing of mobile air
conditioners. The model used requires estimates of five key
parameters. The distributions of possible values for two of
these parameters, air exchange rate, and mixing factor were
assumed to be the same for each exposure scenario modeled. The
distribution of possible values for the remaining three
parameters; room volume, duration of release and emission mass
were varied depending on the exposure scenario being evaluated.
The ranges of values chosen for the air exchange rates and mixing
factors assumed are given below.
Model Input Parameter Range
Air exchange rate(air changes/hour) 1-10
Mixing Factor(dimensionless) 0.3 - 1.0
These ranges of model input parameters are believed to be
representative of current industrial ventilation practices. The
ranges of possible values for the other three model input
parameters are given in Sections 3.7 and 3.8.
There is considerable uncertainty whether the modeled
exposures are truly representative of future CFC substitute
exposures. This uncertainty originates predominantly in
assumptions used for model input variable values such as amounts
of CFC substitutes released into the workplace and ventilation
rates of enclosed spaces where exposures occur. In addition, the
extent to which future differences in work practices and
equipment design will reduce substitute exposures is unknown.
Attempts were made to recognize the potential exposure reduction
of CFC substitute recycling and release prohibitions in the
modeling used to estimate the occupational exposures.
43
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3.3 DATA SOURCES
The major sources of data on occupational exposure cited
in the PEI report include:
o A database maintained by the Occupational Safety
and Health Administration (OSHA) which contains
records on 1400 chemicals regulated by OSHA and
monitored (mostly for enforcement purposes) since
1981.
o Information from National Institute of Occupational
Safety and Health (NIOSH) studies such as Health
Hazard Evaluations (HHEs) and Industry Wide Surveys
(IWSs).
o Information voluntarily submitted to the EPA in
conjunction with responses to requests for
information under Section 114 of the Clean Air Act.
o Information voluntarily submitted to the Agency by
manufacturers and users of CFCs and their
substitutes during the development and review of
this document.
o Modeling techniques which were used to predict
potential exposure levels in the absence of data.
The above data sources only contained data on exposures
through inhalation. It should be noted that the majority of the
personal inhalation monitoring data were taken in response to
complaints and the extent that they accurately characterize
potential exposures without any biases is not known. Therefore
there is no way of knowing whether these data are truly
representative of actual CFC exposures. This uncertainty is
further compounded by the use of existing CFC data as surrogates
for CFC substitutes for many exposure scenarios.
No data on dermal exposure were found. However, the high
volatility of CFCs and many of the substitutes are expected to
significantly limit any dermal exposure. For this reason, dermal
exposures are not addressed in this analysis.
3.4 SUMMARY AMD CONCLUSIONS
Tables 3-4 and 3-5 summarize the results of this
preliminary assessment which are described in more detail in the
following sections by end use. The results presented here rely
heavily on the limited data set for existing CFCs.
44
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TABLE 3-«: ESTIMATED POTENTIAL WORKPLACE EXPOSURES FOR CFC SUBSTITUTES
FOR SCENARIOS WHERE MONITORING DATA IS AVAILABLE(I)
SCENARIO
MANUFACTURE
FOAM BLOWING
Rigid
Flexible
STERILANT CARRIER
ELECTRONICS CLEANING
METAL CLEANING
UIIUDCB nc
SITES
<11
<85
<144
6,000
6,700(4)
12,200(4)
NUMBER 0
PER SITE
50-145
2-10
2-10
5
3
3
F WORKERS
TOTAL
550 TO 1600
170-850
268-1440
30,000
20.100
36,600
8 HR-TWA INHALA1
Mid- range (ppm)
10
20
5
20
10
ION EXPOSURE
Outer-bound (ppm)
100
500
55
3(2)
1000
1000
15 MINUTE PEAK EXPOSURES
(PPM)
<1000
<5000
<550
15(3)
<10,000
<10,000
NOTES
1. Dermal exposure* are expected to be minimal for each scenario.
2. Exposure was based on PEL for Ethylene Oxide.
3. 10 minute exposure.
4. The number of sites assumed to be the same as the number of operating units.
-------
TABLE 1-5: ESTIMATED POTENTIAL WORKPLACE EXPOSURES (1,2) FOR CFC SUBSTITUTES
BASED ON MODELLING TECHNIQUES
SCENARIO
REFRIGERATION SERVICING (3,7)
Retail Food Storage
Cotd Storage Warehouses
Chillers
Industrial Process Coolers (5)
MOBILE AIR-CONDITIONING (4)
Manufacture
Servicing
IHMRFR OF
SITES
....
305,000(6)
76,000(6)
25,000(6)
>1, 000,000(6)
64
329.000
NUMBER (
PER SITE
... — ....
1-2
1-2
1-2
1-2
20
1-5
IF WORKERS
.....
TOTAL
1220-2440
300-600
100-200
8500-25000
1280
329,000 -
1,654,000
8 NR-TUA INHAU
Mid- range (ppm)
20
20
66
14(8)
S3
7
IT I ON EXPOSURES
Outer-bound (ppm)
71
48
171
42(8)
105
21
15 MINUTE PEAK EXPOSURES
(PPM)
497
325
1179
313(8)
158
26
NOTES
1. Denial exposures are expected to be minimal for each scenario.
2. Emission masses for servicing scenarios take into account recycling required by 1990 Clean Air Act
3. Refrigeration exposures were based on modelling using HCFC-22 as a model compound except for chillers which
used HCFC-123
4. Mobile air-conditioning exposures Mere based on modeling using HFC-134a as a model compound.
5. This scenario includes ict machines, skating rinks, and chemical plant and refinery process coolers.
6. The number of sites was assumed to be the same as the number of services per year.
7. Refrigeration includes both coamercial refrigeration and air conditioning.
8. These estimates are for servicing of medium sized ice-machines which make up the bulk of this category.
-------
Additional data characterizing actual HFC/HCFC use and
exposures would improve this assessment. Exposure monitoring
studies of actual worker activities associated with the use of
HFCs/HCFCs are particularly needed to reduce the uncertainties
associated with the current exposure characterization. There are
several important issues that must be considered when developing
plans for monitoring studies to gain additional data-. To ensure
that monitoring data collected is representative of actual
potential exposures, the variables that affect the measured
exposures should be characterized and known to be within the
bounds of what may reasonably be expected to occur in actual
practice. The major variables that are expected to affect
exposures include:
o Worker activities and work practices.
o Quantities and rates of HFC/HCFC used and potentially
released.
o Technologies and equipment used.
o Engineering controls that limit exposures such as
ventilation rates.
o Personal protective equipment.
o Physical/chemical properties such as vapor pressures and
molecular weights. If existing CFCs are used to simulate
the HFCs and HCFCs, then they should have properties that
are similar.
o Concerns regarding the relatively greater toxicity of the
substitutes.
Plans for obtaining monitoring data must also address the issue
of how many measurements are necessary to fill the perceived data
gaps. EPA would like the opportunity to meet with industry to
discuss specific monitoring protocols before any data are
collected.
3.5 MANUFACTURE
HFCs and HCFCs will be manufactured by chlorinating and/or
fluorinating volatile chlorinated solvents in continuously
operating, contained systems.
Because manufacturing plans are still being developed by
industry, the potential number of manufacturing sites and
production volumes for the eight HFCs and HCFCs are unknown.
Based on the average plant capacity data for the existing CFCs,
an average daily throughput for a CFC substitute may be 32,200
47
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kg/site-day. It is assumed that the potential total number of
manufacturing sites will be similar to the number used to
manufacturing current CFCs, which is 11. This number probably
overstates the future markets for HFCs/HCFCs, given their
relatively high costs and the availability of other non-HFC/HCFC
substitutes.
No information was found on the number of workers
potentially exposed at existing or substitute CFC manufacturing
sites. It is estimated that 50 to 145 workers per site could be
exposed. Therefore, the total number of workers exposed is
estimated at 550 to 1600.
Workers could potentially be exposed during quality
control sampling, packaging and shipping, and maintenance
activities. Workers may be exposed for up to 8 hours per day,
250 days per year.
I
Workers at CFC manufacturing facilities typically do not
use personal protective equipment (PPE) to limit inhalation of
CFCs under normal operating conditions. However, the use of
toxic gases such as chlorine in the CFC manufacturing process
requires a substantial amount of engineering controls that
effectively limit exposure to those chemicals. In some
instances, these controls also serve to limit exposure to CFCs.
Occupational exposures to HFCs and HCFCs are expected to
be similar to the existing CFCs because of their similar physical
and chemical properties. Personal monitoring data found for
CFCs, HFCs, and HCFCs (8-hour TWA) are displayed in Table 3-6.
It is not known whether this data set is representative of all
CFC or CFC substitute manufacturing operations. However, it is
believed that outerbound 8-hour TWA exposures to the HFCs and
HCFCs can be expected to be below 100 ppm, if controls that are
commonly found in existing CFC manufacturing environments are
used. The geometric mean of 8-hour exposure data currently
available indicate that mid-range exposures could be less than 10
ppm.
No short-term exposure data for the CFCs, HFCs, or HCFCs
were found. EPA investigations into occupational exposures to
other volatile chlorinated compounds during use in metal and
electronics cleaning and dry cleaning operations indicate that
15-minute ceiling exposures can be an order of magnitude greater
than 8-hour data. Based on these data, outerbound short-term
exposures are estimated to be less than 1000 ppm. There is a
high degree of uncertainty in this estimate due to the difference
in activities that may result in peak exposures.
48
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TABLE 3-6 PERSONAL INHALATION MONITORING DATA (8 HOUR TWA) FOR
THE MANUFACTURE OF CFCS, HFCS, AND HCFC8
CFC
CFC-11
CFC-12
CFC-113
CFC-115
HCFC-22
HCFC-123
HCFC-141b
HCFC-142b
HFC-152a
No. of
sites
2
1
2
1
2
1
1
1
1
No. of
samples
29
25
15
12
18
5
6
6
3
Range Geo. Mean Data
ppm ppm Sources
0.7
0.1
0.1
0.1
- 90.7
-159.0
-108.0
- 34.0
0.01- 11.0
0.2
0.1
0.1
-10.8
- 2.7
- 3.7
1.5
6.4
3.3
5.0
0.9
0.6
0.9
0.5
0.5
NIOSH
114 letter
NIOSH
NIOSH
114 letter
NIOSH
NIOSH
114 letter
114 letter
114 letter
114 letter
NIOSH
3.6 FOAM BLOWING
Currently, CFC-11 and CFC-12 are used as blowing agents in
the manufacture of rigid and flexible polyurethane (FOR) foams.
CFC-11, CFC-12, CFC-113, and CFC-114 are also used as blowing
agents in the production of other foams such as phenolic,
polypropylene, polyethylene, PVC, and polystyrene foams. Foam
production processes using HCFCs are expected to be
technologically similar to those that currently use existing
CFCs. HCFC-22, HCFC-123, HCFC-141b, HCFC-142b may be used in
future foam blowing processes. It should be noted that the new
Clean Air Act bans the use of HCFCs in non-insulating foams in
three years. There is no information indicating that HFCs will
be used in foam blowing.
3.6.1 RIGID PUR FOAMS
Rigid PUR foams are produced by four different processes:
in the form of laminated boardstock; as bunstock; by pour-in-
place/ injection; or by spray technology. There are an estimated
49
-------
85 facilities operated by 55 firms that are major producers of
rigid polyurethane foam. Average CFC throughputs were 2500
kg/site-day for CFC-li-based processes and 170 kg/site-day for
CFC-12-based processes based on 1985 data.
The number of exposed workers for rigid foams is estimated
to range from two to ten workers per site with the lower estimate
for sprayed foam and the higher estimate for boardstock,
bunstock, or slabstock plants. The total number of workers
exposed is estimated to be 170 - 850.
Worker activities in the various foam manufacturing
processes include: formulation of polyol and polyisocyanate
solutions, sampling, monitoring foam machines and foam lines, and
cutting and stacking foam. The presence of isocyanates in the
work area, some of which have OSHA Permissible Exposure Limits
(PELs) less than 1 ppm, may be a factor that minimizes exposure
to CFCs and their substitutes. Workers may perform these
activities for up to 8 hours per day for up to 250 days per year.
No personal protective equipment is known to be routinely used to
limit inhalation exposure to CFCs during foam manufacture.
There were 103 personal inhalation measurements for the
manufacture of rigid foam using CFC-11 with a geometric mean of
18.3 ppm. These monitoring data are presented in Table 3-7,
along with monitoring data for flexible foam. It is not known
whether these data are representative of all foam blowing
operations and, in particular, operations that may use HCFCs.
However, considering the existing CFC data, mid-range exposures
to HCFCs can be expected to be less than 20 ppm during rigid foam
manufacturing, provided that engineering controls and operating
practices similar to those used in existing CFC operations are
used to limit exposure. Outerbound exposures to HCFCs are
expected to be less than 500 ppm.
Limited short-term exposure data for rigid and flexible
foam production were found and are displayed in Table 3-8.
Because none of these data exceeded the maximum 8-hour
measurements noted in Table 3-7, it was assumed that they were
not representative of worst-case, short-term exposures. EPA
investigations into occupational exposures to other chlorinated
volatile compounds during use in metal and electronics cleaning
and dry cleaning operations indicate that 15-minute exposures can
be up to an order of magnitude greater than 8-hour data. Based
on the 8-hour data and the results of the chlorinated volatile
investigations outerbound, short-term occupational exposures are
estimated to be about 5000 ppm for rigid foam. There is a high
degree of uncertainty in this estimate because of the significant
differences in activities that may lead to peak exposures.
Material belongs to:
Office of To:-:-ic .?:*v/vre-, Library -•
50 U.S. !>-• •'••"••:••• ' '•'•'• •-•••.•..:.K'n Agency
401 Ms:-.01 .vV./ir, •:•'•"•
Washivi'-;•!-, O.O. .XMOO
(202)382-3944
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TABLE 3-7 PERSONAL INHALATION MONITORING DATA
(8 HOUR TWA) FOR FOAM BLOWING
Process
Rigid
Rigid
Flex.
Foam
Foam
Foam
CFC
CFC-11
CFC-12
CFC-11
No. of
Sites
16
1
3
No. of
Samples
103
1
46
Range
ppm
0.2 - 540
0.
0.05 - 55.
Geo. Mean
ppm
18.3
07
2 1.4
Data
Sources
NIOSH
OSHA
Industry
NIOSH
NIOSH
OSHA
TABLE 3-8 15-MINUTE PERSONAL INHALATION MONITORING DATA
FOR FOAM BLOWING
No. ofNo. ofRangeGeo. MeanData
Process CFC Sites Samples ppm ppm Sources
Rigid Foam
Rigid Foam
Flex. Foam
CFC-11
CFC-12
CFC-11
2
1
1
5
1
5
11.0 - 310.0
44.0
0.07 - 0.12
44 . 0 NIOSH
OSHA
NIOSH
0.09 NIOSH
OSHA
3.6.2 FLEXIBLE PUR FOAMS
Flexible PUR foams are produced by two main processes in
the form of molded foam articles or slabstock. There are an
estimated 105 facilities producing flexible polyurethane
slabstock and 39 facilities operated by 28 firms producing
flexible polyurethane molded foam. In 1985, an average facility
using CFC-11 in flexible slabstock production had a CFC
throughput of 435 kg/site/day. An average facility using CFC-11
in flexible molded foam production had a throughput of 325
kg/site-day in 1985.
It is expected that many producers of flexible foams will
not convert their processes to HCFC blowing agents because of
their high cost and the availability of cheaper alternatives.
The number of sites using HCFCs as blowing agents for flexible
51
-------
foams are expected to be much less than the number of sites
currently using CFCs.
The number of exposed workers for flexible foams is
estimated to range from two to ten workers per site. The lower
estimate corresponds to sprayed-foam plants while the higher
estimate is associated with boardstock, bunstock, or slabstock
plants. The total number of workers exposed is estimated at 288
- 1440.
Worker activities in the various foam manufacturing
processes are: formulation of polyol and polyisocyanate
solutions, sampling, monitoring foam machines and foam lines, and
cutting and stacking foam. The presence of isocyanates in the
work area, some of which have OSHA Permissible Exposure Limits
(PELs) less than 1 ppm, may be a factor that minimizes exposure
to CFCs and their substitutes. Workers may perform these
activities for up to 8 hours per day for up to 250 days per year.
No personal protective equipment is known to be routinely
used to limit inhalation exposure to CFCs during foam
manufacture.
There were 46 personal inhalation measurements for the
manufacture of flexible foam using CFC-11, with a geometric mean
of 1.4 ppm. These data are presented in Table 3-7. Considering
the existing CFC data, mid-range exposures to HCFCs can be
expected to be less than 5 ppm for flexible foam manufacture,
provided that engineering controls and operating practices
similar to those used in existing CFC operations are used to
limit exposure. Based on available data, outerbound exposures to
HFCs and HCFCs are expected to be less than 55 ppm for flexible
foam. Outerbound short-term occupational exposures are estimated
to be about and 550 ppm for flexible foam production.
3.7 COMMERCIAL REFRIGERATION AND AIR CONDITIONING
CFC-11, CFC-12, CFC-114, and CFC-115, as well as HCFC-22,
are currently used as refrigerants in retail food storage, cold
storage warehouses, chillers, industrial process refrigeration,
as well as in other minor uses. Chillers are defined, for the
purposes of this report, as the cooling systems used in
commercial air conditioning applications. The four major
applications account for a vast majority of the total CFC
consumption for commercial refrigeration and air conditioning.
The substitutes that may be used in the future include HCFC-123,
HCFC-124, HFC-125, HFC-134a, and HFC-152a, as well as continued
use of HCFC-22. Equipment for cold storage warehouses, chillers,
and industrial process refrigeration can be either inside or
outside of a building. Retail food storage equipment is always
inside.
52
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The greatest potential for occupational exposures to CFCs
or their substitutes when used as refrigerants occurs during
servicing. Currently, prior to servicing, a portion of a
refrigeration system's charge may be vented to the atmosphere in
an uncontrolled fashion resulting in exposure to workers.
Recharging vented units may also lead to similar exposures.
However, there are several factors that will change current
worker exposures patterns including: the use of new equipment
designs, which are essential as the CFC substitutes are not drop-
in replacements; mandatory recycling under the Clean Air Act
Amendments, and a prohibition on the venting of CFC substitutes,
also under the Clean Air Act Amendments.
3.7.1 RETAIL FOOD STORAGE
Retail food storage refrigeration systems are used to
refrigerate food (e.g., frozen foods and dairy products) and
beverages in display cases or cabinets. These types of systems
are located in convenience stores, small independent grocery
stores, and large supermarkets. The average refrigerant charge
is about 130 kilograms. There are approximately 305,000 retail
food storage units currently operating. Servicing is estimated
to occur once per year for each unit.
3.7.2 COLD STORAGE WAREHOUSES (CSWs)
Refrigeration systems are employed in CSWs to provide
long-term storage during the distribution process of items such
as meats, produce, dairy products, and other perishable foods.
CSW refrigeration systems include both coolers and freezers. A
typical unit is charged with 11,400 kg of refrigerant. There are
an estimated 18,900 CSWs currently operating that use CFCs or
HCFCs. CSW units are reported to be serviced four times per
year.
3.7.3 CHILLERS
A chiller is a critical part of air conditioning systems
used to cool large buildings, hospitals, and schools. The
chiller system consists of a central refrigeration unit that
"chills" a secondary fluid (e.g., water or brine), which is
circulated through remote heat exchangers to cool air. Typical
refrigerant charge quantities can vary from 65 to 1200 kilograms.
100,000 chillers are currently in operation. Each system may
receive service once every four years.
53
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3.7.4 INDUSTRIAL PROCESS REFRIGERATION
Industrial process refrigeration systems are used for a
wide variety of purposes ranging from storing volatile liquids to
maintaining ice rinks. Process refrigeration may be used in
facilities such as refineries, chemical plants, dairy and meat
packing plants, and ice making plants. The refrigerant may
provide cooling directly to the surface to be cooled or be used
to cool a secondary working fluid. These systems may contain
refrigerant charges that range in size from one to several
thousand kilograms. It is estimated that more than 1 million
industrial process refrigeration units may currently be in
service. Servicing is estimated to occur two to three times per
year.
3.7.5 SERVICING
Assuming one to two workers are exposed during each
servicing, each service takes an entire working day, and each
service employee works 250 days/year, the total number of workers
exposed per year for each application is estimated to be:
retail food storage 1220 - 2440
cold storage warehouses 300 - 600
chillers 100 - 200
industrial process refrigeration 8500 - 25000
No personal protective equipment or engineering controls
are known to be routinely used to limit inhalation exposure to
CFCs during servicing of refrigeration units.
Only six 8-hour personal exposure measurements were
found for workers to CFCs during refrigeration servicing. These
data are presented in Table 3-9. This data set is not extensive
enough to draw conclusions regarding 8-hour exposures. In
addition, no short-term CFC substitute exposure data were found
for workers servicing commercial refrigeration and air
conditioning equipment. Therefore, modeling estimates of
exposures were made using HCFC-22 as a representative compound
for retail food storage, cold storage warehouses and industrial
refrigeration. HCFC-123 was used as a representative compound to
estimate occupational exposures related to servicing of chillers.
The ranges of values of exposure scenario-specific model
inputs used to estimate exposures during commercial refrigeration
and air conditioning servicing were:
54
-------
Room Volume Emission Duration of
fro ) Mass (kg) Release(min)
Retail Food Storage 500-10,000 0.91-3.65 5-30
Cold Storage Warehouses 250-1,000 0.23-0.68 5-30
Chillers 250-1,000 1.25-5.0 5-30
Industrial Process Refrig. 250-1.000 0.45-0.90 5-30
The room volume range chosen for retail food was intended
to encompass the sizes of typical retail food stores. The room
volume ranges for the other applications were intended to
encompass the sizes of small compressor rooms. The ranges of
emission masses used in the modeling were based on assuming that
a portion (generally less than 5% for the above scenarios) of a
cooling system's refrigerant charge is vented during servicing.
These estimates of emission mass assume some portion of the
refrigerant charge is recycled. Emissions into the workplace
were assumed to last from 5 to 30 minutes.
Mid-range and outerbound exposures were modeled to be:
8-hour TWA 8-hour TWA 15-minute
Mid-range Outerbound Outerbound
ppm ppm ppm
Retail Food Storage 20 71 497
Cold Storage Warehouses 20 48 325
Chillers 66 171 1179
Industrial Process Refrig. 21 71 476
TABLE 3-9 PERSONAL INHALATION MONITORING DATA (8 HOUR TWA)
FOR SERVICING OF REFRIGERATION UNITS*
CFC
CFC-12
CFC-115
HCFC-22
No. of
Samples
2
2
2
Range
ppm
0.7
1.6 - 2.2
0.8 - 1.4
Data
Source
OSHA
NIOSH
NIOSH
Each line of data represents measurements at a single site.
A recent Finish (Antti, 1990) paper included data on short-term
HCFC-22 exposures experienced during refrigerator repair work.
The exposures presented ranged from 1300 to 10,000 ppm. The
duration of the exposures were cited to be 70 to 150 minutes.
55
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3.8 MOBILE AIR-CONDITIONING
Currently, CFC-12 is the only CFC used in mobile air-
conditioning. HCFC-22, HCFC-124, HCFC-142b, HFC-134a, and HFC-
152a may be used in the future.
3.8.1 MANUFACTURING
Mobile air conditioners (MACs) are refrigeration systems
that are installed in motor vehicles to provide cooling in the
passenger area. MACs are installed in automobiles, light-duty
trucks, heavy-duty trucks, and buses during vehicle manufacture
as original equipment.
There are 64 vehicle manufacturing sites in the U.S. where
MACs are installed in vehicles. In 1985, U.S. production of
motor vehicles was approximately 11.7 million vehicles. A
typical charge of CFC-12 in MACs is approximately 1 kilogram.
It is estimated that up to 20 workers per manufacturing
site will be involved in this activity. The total number of
workers potentially exposed to CFC substitutes during MAC
manufacture is estimated to be 1280.
The process for charging MACs with HFCs/HCFCs during
vehicle manufacture is expected to be similar to existing
operations. Although HFCs and HCFCs are comparable with the
current MAC systems, some necessary modifications prevent them
from being drop-in substitutes. MAC compressors will have to be
redesigned to compensate for efficiency losses resulting from the
inherent chemical properties of the HFCs and HCFCs. Use of
substitutes may also require the development of alternate
compressor oils and hose material. Increased costs of
refrigerants may result in greater emphasis on recovery and
recycle systems prior to servicing or disposal of motor vehicles.
No 8-hour TWA monitoring data were found for charging MAC
units at auto manufacturing sites. However, monitoring data were
found for the charging of refrigerants to household refrigerators
at assembly plants, which is a similar operation. Personal
inhalation exposures of CFC-12 in this study ranged from 0.7 to
4.9 ppm. The same model used to estimate exposures in
refrigeration servicing was used to predict 8-hour mid-range and
outerbound exposures of 53 and 105 ppm respectively. HFC-134a
was the modelled substitute.
For modeling purposes, MAC manfacturing room volumes were
assumed to be 5,000 to 20,000 m3. The emission mass range was
based on an analogy to measured releases during manufacturing of
household refrigerators. Emissions to the workplace were assumed
to last from 5 to 30 minutes.
56
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No short-term exposure data was found for auto
manufacturing sites. The model that was used to predict
exposures in refrigeration servicing predicted 15-minute
exposures of 158 ppm.
3.8.2 SERVICING
MAC system repairs are performed in factory-authorized
shops, independent repair shops, and by the vehicle owner. The
number of service sites in the U.S. was estimated in 1986 to be
329,000. The number of NACs serviced per site per year may range
from 11 for a fleet maintenance shop to 170 for a new car/truck
dealer.
The number of workers servicing MA.Cs is estimated to be
from 1 to 5 per site. The total number of workers potentially
exposed to HFCs/HCFCs during MAC servicing is estimated to range
from 329,000 to 1,654,000.
Prior to servicing, MAC units are frequently vented to the
atmosphere in an uncontrolled manner. Recharging, after
servicing, is performed manually. The recharging is usually
accomplished by connecting a pressurized container of refrigerant
to the MAC. Recharging can also be performed using prepackaged
aerosol cans of refrigerant.
Servicing and recharging practices are expected to be
modified for the HFCs and HCFCs. It is anticipated that recovery
units will be put into service to recover the used refrigerant
that had been vented prior to servicing, thereby limiting
environmental releases and worker exposure. Some states are
enacting recycling legislation, and the anticipated Clean Air Act
amendments would require mandatory recycling of MAC refrigerants.
These systems would have to purify recovered refrigerant before
it could be returned to MAC systems for reuse.
No personal protective equipment are known to be routinely
used to limit inhalation to CFCs during the MAC recharging or
servicing. Some service sites may have ventilation systems to
dilute potential exposures when service is performed in service
bays with closed doors.
No data on 8-hour or short term occupational exposures to
CFCs or their substitutes were found for MAC service sites.
Estimates of occupational exposures during MAC recharging and
servicing (venting and recharging) were developed using the same
model used in refrigeration servicing. HCFC-l34a was the
compound used in the modeling. An outerbound modeling estimate
of 8-hour exposure with recycling is 21 ppm. An outerbound
estimate of 15-minute exposures with recycling is 26 ppm.
57
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For modeling purposes, MAC servicing room volumes were
assumed to range from 250 to 10,000 m3. This range was intended
to encompass service facilities that have one to several service
bays. The emission mass range was based on information on
average release quantities during servicing. These estimates of
emission mass assume some portion of the refrigerant charge is
recycled. Emissions to the workplace were assumed to last 5 to
20 minutes.
3.9 STERILANT CARRIER
Currently, CFC-12 is the only CFC used as a sterilant
carrier. In this application, CFC-12 is used as a flame
suppressant carrier for ethylene oxide, which is used to destroy
bacteria, viruses, and fungi present on contaminated hospital
equipment. CFC-12's function is to serve as an inert diluent to
reduce the flammability concerns associated with handling pure
ethylene oxide. The ethylene oxide/CFC-12 mixture makes contact
with the contaminated hospital equipment in sealed vessels.
HCFC-123, HCFC-124, and HCFC-141b are potential substitutes for
CFC-12 due to similar physical properties.
A 1977 source estimates that there are about 6,000
hospitals in the U.S. that have sterilizers. Host hospitals
operate more than one sterilizer. NIOSH National Occupational
Hazard Survey (NOHS) data indicate that approximately 30,000
workers in the health care field are potentially exposed to CFC-
12 in sterilant use. Based on the above data, there would be an
average of 5 workers per site.
Worker activities for sterilization operation include
loading, operating, and unloading sterilizers; transferring
sterilized articles to aerators; unloading aerators; and putting
the articles into a sterilized storage area. There are also
workers involved in washing instruments and carts, folding
linens, and wrapping and packaging items for sterilization.
Typically, engineering controls are used to limit exposure
to ethylene oxide. These include a dedicated local exhaust
ventilation that directs air away from areas in which workers
function. The only personal protective equipment expected to be
used is gloves, which are used when removing sterilized articles.
No exposure data were found for CFC substitutes. A
limited amount of personal monitoring data for CFC-12 used as a
sterilant was found. Table 3-10 presents a summary of these
data. These data are probably not relevant to this assessment
because the OSHA PEL for ethylene oxide has recently been reduced
to 1 ppm. Using the new OSHA PEL coupled with adjustments for
differences in vapor pressures and solution concentrations,
exposures to CFC substitutes are estimated to be about 3 ppm.
58
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Short term (15 minute) HFC/HCFC exposures are estimated to
be less than 15 ppm. This estimate was developed by considering
the recently modified NIOSH Recommended Exposure Limit (REL),
which is a 10 minute ceiling, for ethylene oxide and adjusting
this value for differences between CFC-12 and ethylene oxide
vapor pressures.
TABLE 3-10 PERSONAL INHALATION MONITORING DATA (8 HOUR TWA)
FOR CFC-12 USE AS A 8TERILANT CARRIER*
NO. Of
samples
3
1
4
1
Range
ppm
1.3 - 27.9
0.5
0.9 - 32.0
1482.7
Data
Source
NIOSH
NIOSH
OSHA
OSHAb
b
Each line of data represents measurements at a single site.
This measurement was taken at a facility which has been out of
business since 1981.
3.10 ELECTRONICS AND METAL CLEANING
CFC-113 is used in the electronics industry to clean
printed circuit (PC) boards and other equipment. It also has
applications in a variety of other manufacturing and service
industries to degrease and clean metal parts. Although CFC-113
is the only existing CFC which is currently used extensively in
these applications, methyl chloroform as well as several other
chlorinated solvents are also used. CFC-113 usage has been
greatest in areas requiring "precision" cleaning. HCFC-123 and
HCFC-141b may be used in the electronics and metal cleaning
applications in the future. An azeotrope of these two HCFCs and
methanol is particularly promising for PC board cleaning.
There are two major types of cleaning processes in which
CFC-113 is used: vapor degreasing and cold cleaning. Vapor
degreasers are used primarily in electronics industry
applications. There are an estimated 6000 vapor degreasers
operated by the electronics industry. An additional 700 units
are used to clean other kinds of electronic cleaning operations.
Annual CFC-113 consumption in electronics applications is
estimated to be 26 million kilograms per year.
59
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There are an estimated 12,200 vapor degreasers and cold
cleaning units operated to clean metal parts. This cleaning may
be necessary for subsequent assembly, painting, welding,
electroplating, and further inspection. Approximately 43 million
kilograms of CFC-113 are consumed per year for these uses.
An estimated 3 workers per cleaning unit are potentially
exposed to CFC-113 during electronics and metal cleaning
operations. Worker activities that may contribute to exposure
include transfer of CFC solvent to cleaning equipment, handling
of cleaned articles during their removal from the cleaners, and
disposal of dirty solvent.
No information was found on personal protective equipment
used in solvent cleaning operations. Ventilation is used
frequently to limit worker exposure. Engineering controls and
operating practices that limit CFC loss, such as keeping
equipment sealed, positioning work to minimize drag out, and
directing solvent sprays below vapor levels, will also reduce
occupational exposures.
Table 3-11 displays pertinent occupational exposure data
for CFC-113-based electronics and metal cleaning operations. The
geometric means of the data indicate that mid-range or expected
likely exposures for PC Board Cleaning can be expected to be less
than 20 ppm and less than 10 ppm for metal cleaning. Given the
range of the CFC-113 data, workers attending similar HCFC-based
operations in the future can be expected to have outerbound 8-
hour exposures of less than 1000 ppm.
TABLE 3-11 PERSONAL INHALATION MONITORING DATA (8 HOUR TWA)
FOR CFC-113 IN ELECTRONICS AND METAL CLEANING
No. ofNo. ofRangeGeo. MeanData
Process sites samples ppm ppm Source
PC Boards 16 62 0,04 - 890.0 19.3 NIOSH
OSHA
Industry
Other Elect. 48 144 0.001 - 970.0 8.1 NIOSH
Cleaning OSHA
Metal 29 55 0.04 - 730.0 8.3 NIOSH
Cleaning OSHA
60
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Table 3-12 displays short-term data for CFC-113. Short-
term exposures to CFC substitutes are hard to gauge with this
limited amount: of data. EPA has gathered data on worker
exposures to methylene chloride during electronics cleaning and
trichloroethylene during vapor degreasing. These data indicate
that outerbound short-term HFC/HCFC exposures during electronics
and metal cleaning should be less than an order of magnitude
greater than the 8-hour data or 10,000 ppm.
TABLE 3-12 15 MINUTE PERSONAL INHALATION MONITORING DATA
FOR CFC-113 IN ELECTRONICS AND METAL CLEANING
No. of. No. of Range Geo. Mean Data
Process sites samples ppm ppm Source
Other Elect. 4 10 3.1 - 330 73.7 NIOSH
Cleaning OSHA
61
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4. CONSUMER EXPOSURE
This section presents a summary of EPA's assessment of the
potential exposures to consumers which could occur from the use
of the HFCs and HCFCs. Since no exposure data for these
chemicals existed, the exposure assessment was based on analogies
to present CFC use exposure.
This assessment estimates amounts of individual exposure
and the populations exposed for representative scenarios.
Because of EPA's mission to safeguard human health, these
exposures have been estimated conservatively; that is, the
assumptions selected in the estimation process have in some cases
tended to drive estimates of exposure to the high end of the
range. These exposure and population values are believed to be
possible based on the information presently available. In these
estimates, it has been assumed that the HFCs and HCFCs will
completely replace present CFCs in both the type and extent of
use described. The maximum exposures reported are not likely to
apply to the entire exposed population.
The consumer product use scenarios discussed in this
report are a few of the applications that may cause exposures to
CFC substitutes. They were selected because they satisfied at
least one of the following conditions: large percentages of CFCs
are used in the application; the application was believed to have
a greater potential for either short-term high exposures or long-
term lower level exposures when compared to other applications;
and information useful to the assessment was readily available
for the application. Consumer exposure to CFCs, and by analogy
HFCs and HCFCs, is estimated for the following scenarios:
refrigerated home appliances, motor vehicle air conditioning, and
video tape head cleaners. Table 4-1 presents the estimated
exposures and the exposed populations.
Two other uses which meet the preceding conditions are
rigid closed cell foam insulation and rigid polystyrene foam used
in food packaging. Consumer exposures to emissions from foam
insulation are not estimated here because an industry-sponsored
foam insulation testing program is currently underway which is
intended to provide more complete blowing agent emission rate
data than that currently available. Consumer exposure is also
not estimated here for food packaging, which is subject to Food
and Drug Administration regulations.
62
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TABLE 4-1 POTENTIAL CONSUMER INHALATION EXPOSURES TO HFCs/HCFCs
Scenarios
Exposures
(mg/yr)
Exposure
population
sizes
Household Appliances (Normal leakage)
Refrigerator1*
10th percentile house0
Mean housed
Freezer6
10th percentile house
Mean house
Dehumidifier
10th percentile house
Mean house
(Service emission*)
10th percentile
Mean
5.1 or 15.3
2.1 or 6.5
10.2 or 20.4
4.3 or 8.6
14.7
6.2
1529
647
12.5 x 106 each
87.5 x 106 each
5.5 x 10a each
38.5 x 106 each
2.4 x 103
1.7 x 10*
NA
NA
Mobile Air Conditioners (System leakage*)
Subcompact
Compact
Midsize
Large
(Recharging)
Video Taue Head Cleaners
0.76 or 167
1.09 or 218
1.37 or 240
1.61 or 259
865
21
7.2 X 10°
8.4 X 106
16.8 X 106
13.5 X 106
2.1 X 106
55 X 106
levels of exposure estimated for each scenario is not known.
Maximum exposures are not likely to apply to the entire exposed
population. Populations estimated for the 10th percentile volume
house are one-tenth of the total estimated exposed population.
Those estimated for the mean volume house are 70 percent of the
total estimated exposed population.
6 Refrigerators and freezers may have either reciprocating or
rotary compressors. The former require less charge and are
estimated to have proportionately lower emissions, and the lower
estimated exposures shown here.
c The 10th percentile house volume equalled 174 m .
d The mean house volume equalled 411 m .
" Service emissions are estimated to occur once every 13 years.
f System leakage may be in engine compartment or in evaporator
case. The latter causes the higher exposures to vehicle
passengers shown here.
63
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The range in appliance exposure estimates are due to
different house volumes and charge sizes. Differences in motor
vehicle air conditioning exposure estimates are from different
leak locations and passenger compartment volumes.
Sources of uncertainty for each scenario are as follows:
o In the home appliance scenario, limited information was
available for differences in the size and frequency of
service releases. Refrigerant reclamation and recycling
during servicing would be expected to lower or eliminate
the service releases.
o In the automobile air conditioning refrigerant leakage
scenario, the chief uncertainties are: the fraction of
refrigerant leakages that occur inside the evaporator case
versus those outside the case, the actual fraction of the
leakage outside the evaporator case that enters the
passenger compartment, and data on automobile air exchange
rates.
o In the scenario for use of video tape head cleaners, a
critical uncertainty is the amount of replacement of the
CFC cleaners by new chemicals versus other presently
available substitutes, i.e., alcohol.
Data on actual HFC/HCFC exposures to consumers would
greatly improve this assessment. Additional information could be
gathered as a precursor to field measurements, emissions
(chamber) testing, and model development. As an example,
representatives of the foam insulation industry are presently
pursuing limited emissions testing of their products to assist in
data development needs. These steps are discussed further in the
consumer exposure support document.
64
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5. GENERAL POPULATION EXPOSURE
This section estimates the potential exposures to the
general population from the manufacture and commercial use of the
HFCs and HCFCs.
5.1 ENVIRONMENTAL FATE
Because the HFCs/HCFCs are very volatile, they are
expected to migrate to the atmosphere as gases. These chemicals
pose some ozone depletion and global warming concerns. An
extensive discussion of ozone depletion and global warming can be
found in Scientific Assessment of Stratospheric Ozone: 1989, Vol
I and II, published by the World Meteorological Organization as
the Global Ozone Research and Monitoring Project - Report # 20.
5.2 ENVIRONMENTAL RELEASE AND EXPOSURE
The release data information available to EPA at the time
of this report was "generic", that is, representative of the
HFC/HCFC amounts which may be released for the given activity.
These release data are summarized in Table 5-1. Since there is
no current data on HFCs and HCFCs, the release estimates are
based on current average CFC releases. Actual HFC/HCFC releases
may be lower than current CFC releases both in total and per
site. This is because new Clean Air Act emission regulations and
potentially higher costs of the HFCs and HCFCs are expected to
cause more conservative use, more reclamation and recycling, or
use of other substitutes. Lack of data makes it impossible to
determine what actual reductions in releases may be.
The Toxic Release Inventory was used to estimate releases
from manufacturing and electronics and metal-cleaning by type,
i.e., stack or fugitive, other stack/fugitive release estimates
were based on a number of other sources and professional
judgment.
65
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TABLE 5-1 HFCs/HCFCs AMBIENT RELEASE ESTIMATES
Activitv
Manufacture
Foam Blowing
- Rigid
- Flexible
Mobile Air Conditioning
- Manufacture
- Servicing
*
sites
11
85
144
(MAC)
64
329,000
Release
days/year
350
250
250
250
11 to 170
Release
(kg/site-day)
Stack Fuaitive1
93 34
195 20
390 45
56
0.3 to 4.3
Sterilization
6,000
Electronics and Metal Cleaning
- PC Board Cleaning 705
- Other Electronics 82
- Metal Cleaning 1,435
Refrigeration
- Retail Food Storage
Manuf/Install. 33,200
Servicing 304,520
- Cold Storage Warehouses
Manuf/Install. 1600
Servicing 18,900
- Chillers
Manuf/Install. 4,260
Servicing 25,000
Industrial Process Refrigeration
- Ice Machines
Manufacture
Medium
Large
X-large
Servicing
Medium
Large
X-large
- Chemical Processing
Manuf/Install
Servicing
- Refineries
Manufacture
Servicing
- Ice Skating Rinks
Manufacture
Servicing
365
250
250
250
1
1
1
4
1
1
127,112
8
1
1,060,000
150
20
C* 1 Y^ff
sing
182
4,000
2
26
Ve
JCS
10
200
1
1
1
3
3
3
1
1
1
1
1
1
42
36
36
98
86
86
20
8
273
76
28
118
0.15
2.1
32
0.1
0.6
8.5
1,436
2,240
1,436
2,270
202
320
1
These estimates assume unregulated venting and will be lower
for HCFC/HFCs based on controls mandated by the Clean Air Act.
66
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Because most of the site locations corresponding to the
release data are unknown, the usual exposure estimation technique
of utilizing site-specific meteorological and population
information to estimate concentrations and the populations
exposed at those concentrations was not utilized. Instead, a
generic site was selected for its meteorological information
only. The ramifications of this selection are discussed in
Section 5-2.
Concentration and exposure estimates based on the release
estimates are presented in Table 5-2. The concentrations
presented were estimated using the EPA Industrial Source Complex
Long Term (ISCLT) Dispersion Model. Exposures were calculated
from these concentrations using the equation:
E = (C x I)/BW
where E is the exposure in mg/kg-day, C is the annual average
concentration in mg/m3, I is the inhalation rate in m3/day (20
m ) , and BW is the average body weight in kilograms (70 kg).
Each exposed individual is assumed to live and work in the same
ambient zone of concentration 24 hours a day year-round through a
70 year lifetime. Since this zone could be located near several
release sources, the exposed individual's overall exposure could
be the sum of multiple exposures, although not necessarily at the
maximum concentrations presented here. The probability of
multiple exposures is expected to be small.
5.2 UNCERTAINTIES IN RELEASE, CONCENTRATION, AND EXPOSURE
ESTIMATES
To make use of these estimates, it is important to
understand the uncertainties associated with them. Considerable
uncertainty is associated with the release estimates because much
of the data were based on analogy to existing CFCs, which will
have differences in physical and chemical properties, material
quantities, equipment design, and emission controls compared to
the HFCs/HCFCs. Since it was not possible to factor in all of
the variables, these results may be higher than actual releases.
Since the concentration and exposure estimates were
derived from the estimated releases, it follows that there are
uncertainties associated with these values as well. There were
additional uncertainties associated with the estimation of the
concentrations to which people may be exposed. A major source of
uncertainty was the need to use a generic site location to
evaluate aerial releases because insufficient information was
available to select specific release sites. This generic site
was selected from an analysis of maximum exposed individual (MEI)
concentrations calculated for an identical release from each of
392 sites across the U. S. These MEIs were calculated from ISCLT
model runs of statistical wind summaries available for the 392
sites.
67
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TABLE 5-2 POTENTIAL AMBIENT INHALATION EXPOSURES TO HFCS/HCFCS
Highest life-
Maximum exposure time exposure**
Activity concentration (ug/m ) (mg/kg-d)
Manufacture
- Stack Release
- Nonstack Release
Foam Blowing, Rigid
- Stack Release
- Nonstack Release*
Foam Blowing, Flexible
- Stack Release
- Nonstack Release*
Mobile Air Conditioning (MAC)
- Manufacture*
- Servicing* 5.
Sterilization
- Stack Release
- Nonstack Release
Electronics and Metal Cleaning
- PC Board Cleaning
- Stack Release
- Nonstack Release*
- Other Electronics
- Stack Release
- Nonstack Release*
- Metal Cleaning
- Stack Release
- Nonstack Release*
Refrigeration
- Retail Food Storage
- Manuf /Install .*
- Servicing*
- Cold Storage Warehouses
- Manuf /Install .*
- Servicing*
- Chillers
- Manuf/Install.*
- Servicing
9.2
22.8
9.6
9.9
19.2
22.3
26.4
3 to 22.9
0.043
0.98
3.2
128
2.7
319
2.7
115
0.15
0.22
0.88
0.96
0.17
0.17
2.6 X 10"3
6.5 X 10*3
9
2.7 X 10"3
2.8 X 10"3
9
5.5 X 10"3
6.4 X 10"3
T
7.6 X 10 3
1.5 (to 6.5) X 10"3
1.2 X 10"5
2.8 X 10"4
/
9.1 X 10 4
3.7 X 10"2
7.7 X 10"4
9.1 X 10"2
.£
7.7 X 10 4
3.3 X 10*2
c
4.4 X 10"5
6.3 X 10"5
.L
2.5 X 10 4
2.8 X 10'4
4.8 X 10"5
4.8 X 10"5
- Industrial Process Refrigeration
- Ice Machines
- Manufacture*
- Medium
- Large
- X-large
- Servicing*
- Medium
- Large
- X-large
0.001
0.014
0.21
0.005
0.03
0.42
3.0 X 10"7
4.0 X 10"6
6.1 X 10"5
•A
1.4 X 10 6
8.6 X 10*6
1.2 X 10"4
68
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TABLE 5-2 (cont)
Highest life-
Maximum exposure time exposure6
Activity concentration8 (ug/m3) (mg/kg-d)
- Chemical Processing
- Manufacture 2.8 8.0 x 10~4
- Servicing 39.9 1.1 x 10~2
- Refineries
- Manufacture 2.8 8.0 x 10~4
- Servicing 39.9 1.1 x 10"2
- Ice Skating Rinks
- Manufacture 1.6 4.6 x 10"4
- Servicing 7.7 2.2 x 10~3
a The concentrations presented were estimated using the EPA
Industrial Source Complex Long Term (ISCLT) Dispersion
Model.These concentrations are the maximum possible at or beyond
site fencelines. Because of data limitations, concentrations for
activities marked with an asterisk (*) could not be estimated at
the fenceline, but only at some point beyond the fenceline.
Because of this, those activities may have larger concentrations
between the fenceline and the point estimated than presented
here.
b The Highest Lifetime Exposure (E) = (C x I)/BW, where:
C = maximum annual average concentration (mg/m3)
I = inhalation rate (20 m /day)
BW = average body weight (70 kg)
Example calculation:
(22.4 ug/m3 x 1 mg/1000 ug x 20 m3/d)/70 kg =
6.4 x 10'3 ma/ka-d
Exposures are conservatively assumed to be 24 hours a day,
year-round, for a 70 year lifetime.
The effects of this type of use of a generic release site
were twofold. First, the meteorological conditions (prevailing
winds, etc.) at the site selected were known to cause
conservative (i.e., high) maximum concentrations resulting in
upper-bound exposure estimates. It is important to note,
however, that the maximum concentration for this site in the
sensitivity analysis was only about twice the lowest maximum
concentration calculated. Second, using a generic release site
does not permit an estimate of how many people, if any, are
exposed at the estimated air concentrations of the HFCs and
HCFCs.
69
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The estimates of model parameters for stack and fugitive
releases are obvious sources of uncertainty because they are
based on professional judgment assumptions about the facilities
at the release point.
Model parameters such as the type of release, release
height, and size of release facility are key determinants of
downwind ambient air concentrations. For example, a volume
fugitive release, which is typically a release from building
ventilators, will cause higher ambient air concentrations than an
area release of the same size. Also, a stack release at a 30
meter height will have its maximum concentration further from the
source than the same release from a 5-meter stack.
The facility fenceline distance estimates were also
assumed. These distances are not used in the ISCLT model itself,
but are compared to the distances the model predicts that release
concentrations will be from the release source. Only those
concentrations beyond the assumed fenceline distance are
considered available for general population exposure. An
additional uncertainty regarding fenceline estimates is that
although the exposures presented here were calculated from the
maximum concentrations predicted by the ISCLT aerial release
model, there were insufficient data available to estimate
concentrations within certain distances of assumed building
source releases. This means that releases from buildings with
fencelines within these distances of unknown concentrations may
or may not have larger concentrations than the model could
predict. The activities where this occurred are marked in Table
5-2; the concentration values used in these instances are the
maximum the model could predict.
It is important to understand that these maximum
concentrations are defined by a particular direction as well.
For example, the area of maximum concentration for a release
might be said to be 200 meters from a source on a westerly
heading. In other directions and further away from the source of
release, the concentrations will decrease.
5.3. OTHER AMBIENT RELEASES
Direct releases to environmental media other than air are
only estimated for HFC/HCFC manufacture, assuming 11 sites and
350 days release per year. The receiving media and release
amount, in kg/site-day, are:
water: 0.1
landfill: 0.07
incineration: 21
underground injection: 8.5
Because of the high vapor pressures of the HFCs and HCFCs,
any disposal method that is exposed to air is expected to result
in volatilization of the substitutes. HFC/HCFC release after
70
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incineration is expected to be <0.1 kg/site-day, assuming a 99.9
percent destruction. Because many of the HFCs/HCFCs are somewhat
soluble in water, their underground injection disposal in aqueous
materials could lower their volatilization. The possibility of
migration of the injected material into groundwater used for
drinking water depends on regulation of the injection site. For
example, hazardous waste injection sites are segregated from
potable groundwater supplies. Present CFCs are federally
regulated as hazardous wastes for certain solvent uses or if
contaminated with hazardous materials. There may also be
additional state regulations. Regulation of HFC/HCFC materials
used as CFC substitutes is expected to be similar.
Although HFC/HCFC releases to water, landfill, and
incineration may eventually volatilize to air, these release
amounts cannot be summed with the air releases previously
presented because their release sites may be spatially distant
from the manufacturing sites. Because of these uncertainties,
and the small sizes of these releases compared to the direct air
releases, exposures were not calculated for these releases, or
the injection release.
71
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EPA SUPPORT DOCUMENTS
PEI Associates, inc. 1990. Occupational Exposure and Environmental
Release Data for Chlorofluorocarbons (CFCs) and their Substitutes.
Prepared under Contract No. 68-D8-0112 for Office of Toxic
Substances, U.S. EPA.
Versar, Inc. 1990. Consumer Exposure to Chlorinated Fluorocarbons
(CFCs) and CFC Substitutes. Prepared under Contract No. 68-D9-0166
for Office of Toxic Substances, U.S. EPA.
U.S. EPA, Office of Toxic Substances. 1990. Interim Hazard
Assessment of HFCs/HCFCs.
U.S. EPA, Office of Toxic Substances. 1990. Potential Ambient
Inhalation Exposures for Chlorofluorocarbon Substitutes.
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-------
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