FINAL GRAFT
United States FPAQ-CIN-G095
Env.ronmental Protection ..,,«„«
Agency April, 1990
&EPA Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR 1.1.2-TRICHLORO-1,2,2-TRIFLUOROETHANE
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
DRAFT: 00 NOT CITE OR QUOTE
NOTICE
This document 1s a preliminary draft. It has not been formally released
iv the U.S. Environmental Protection Agency and should not at this stage be
•onstrued to represent Agency policy. It Is being circulated for comments
in Us technical accuracy and policy Implications.
-------
DISCLAIMER
This report Is an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
-------
PKtCAtt
Health and Environmental Effects Documents (HEEOs) are prepared for the
Office of Solid Waste and Emergency Response (OSUER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained for Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for In this document
and the dates searched are Included In "Appendix: Literature Searched."
Literature search material Is current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates (front
cover) reflect the date the document Is sent to the Program Officer (OSUER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfDs)
for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfO Is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval I.e.. for an Interval that
does not constitute a significant portion of the Hfespan. This type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfOs Is the same as traditionally employed for chronic estimates.
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, a carcinogenic potency factor, or
q-|* (U.S. EPA, 1980), Is provided. These potency estimates are derived
for both oral and Inhalation exposures where possible. In addition, unit
risk estimates for air and drinking water are presented based on Inhalation
and oral data, respectively. An RfO may also be derived for the noncarclno-
genlc health effects of compounds that are also carcinogenic.
Reportable quantities (RQs) based on both chronic toxlclty and cardno-
genlclty are derived. The RQ Is used to determine the quantity of a hazard-
ous substance for which notification Is required In the event of a release
as specified under the Comprehensive Environmental Response. Compensation
and Liability Act (CERCLA). These two RQs (chronic toxlclty and cardno-
genlclty) represent two of six scores developed (the remaining four reflect
IgnltabllUy, reactivity, aquatic toxlclty, and acute mammalian toxlclty).
Chemical-specific RQs reflect the lowest of these six primary criteria. The
methodology for chronic toxlclty and cancer Based RQs are defined 1n U.S.
EPA. 1984 and 1986a, respectively.
111
-------
EXECUTIVE SUMMARY
l,l,2-Tr1chloro-l,2,2-tr1fluoroethane Is a colorless, volatile liquid
with a sweet odor (Hawley. 1981; Verschueren, 1983). 1,1,2-Trlchloro-l,2,2-
trlfluoroethane Is manufactured by reacting hexachloroethane with hydrogen
fluoride In the presence of a catalyst (Smart, 1980). The extent of
chlorine atom replacement Is controlled by varying the concentration of
hydrogen fluoride and the reaction time and temperature. No production data
are available. It Is used primarily as a solvent (Borchers et al.. 1987).
The key factors affecting the fate of 1,1,2-tr1chloro-l,2,2-tr1fluoro-
ethane In the environment are Us very high vapor pressure, combined with
Us low solubility In water and chemical Inertness. The Henry's Law
constant for 1,1,2-trlchloro-l,2,2-tr1fluoroethane calculated from Us vapor
pressure, 330 mm Hg at 2S*C (Parrlsh. 1983). and water solubility, 170
mg/t (Smart. 1980), Is 0.48 atm-mVmol. Therefore, Us volatilization
from water will be very rapid, with the volatilization rate limited by Us
diffusion through water. The half-life of 1.1,2-tr1chloro-l,2.2-tr1fluoro-
ethane In a model river 1 m deep, flowing at 1 m/sec. with a wind of 3 m/sec
1s estimated to be 4.0 hours (Thomas, 1982). Experimental data regarding
the adsorption of I.l,2-tr1chloro-l,2.2-tr1fluoroethane to soil, sediment
and suspended solids In the water column were not located In the available
literature, and a K of 426 was estimated from Us water solubility (see
Section 2.1.). This moderate K Indicates that adsorption to sediment
and participate matter In the water column would not compete effectively
with volatilization from water. Because of 1i,l ,2-tr1chloro-l,2,2-tr1fluoro-
ethane's high vapor pressure, high Henry's Law constant and moderate adsorp-
tion to soil, 1,1,2-trlchloro-l ,2,2-tMfluoroethane would also be expected
1v
-------
to volatilize rapidly from both dry and moist soil. Its K of 426 would
Indicate a moderate potential for leaching Into groundwater (Swann et al..
1983).
Pertinent data regarding the fate of I,l,2-tr1chloro-l ,2,2-tMfluoro-
ethane In water or soil as a result of mlcroblal or chemical reactions or
Interaction with sunlight were not located 1n the available literature cited
In Appendix A. Under environmental conditions, alkyl fluorides are likely
to hydrolyze too slowly for this pathway to be significant (Mabey and Mill.
1978). Fluorocarbons are highly resistant to attack by oxidizing agents
under environmental conditions (Howard et al.. 1975}. Lacking any UV
absorption >290 nm (Hubrlch and Stahl. 1980). direct photolysis should not
be significant. While no Information was found concerning the blodegrada-
tlon of 1.1.2-tr1chloro-l,2.2-tr1fluoroethane, ' its rapid volatilization
would limit. If not preclude, blodegradatlon (Howard et al.. 1975); there-
fore, U Is unlikely that photooxldatlon. hydrolysis or blodegradatlon will
be significant In water or soil.
Pertinent data regarding the bloconcentratlon of I,l,2-tr1chloro-l,2,2-
trlfluoroethane In fish and aquatic organisms were not located In the
available literature. The estimated BCF. 148 (see Section 2.1.). Indicates
that I,l,2-tr1chloro-l.2.2-tr1fluoroethane should have a low potential for
bloconcentratlng In aquatic organisms.
As a result of Us high volatility. I.l,2-tr1chloro-l.2.2-tr1fluoro-
ethane will partition Into air. l,l,2-Tr1chloro-l,2.2-tr1f1uoroethane Is
extremely stable 1n the troposphere (Borchers et al.. 1987); 1t will not
directly photolyze or react with photochemically produced hydroxyl radicals.
It will disperse over the globe and diffuse slowly Into the stratosphere,
where It will be destroyed by photolysis, by short wave-length UV radiation
-------
and, to a lesser degree, by 0{1D) attack (Borchers et al., 1987). An
Intensive 7-year study monitored 1,1,2-trlchloro-l,2,2-trlfluoroethane
weekly at seven locations ranging from the arctic to the antarctic regions.
The data applied to a global mass balance equation resulted 1n a half-life
of 48.5 years {Khalll and Rasmussen, 1988). Therefore, the 1,1,2-trlchloro-
1,2.2-trlfluoroethane released to air would be expected to accumulate there.
Its concentration In the atmosphere, removed from local sources, would be
fairly uniform over the world. l,l,2-Tr1chloro-l,2,2-tr1fluoroethane will
be removed from the atmosphere by dry and wet deposition and will return to
.the atmosphere by volatilization.
•i
• l,l,2-Tr1chloro-l,2,2-tr1fluoroethane Is ubiquitous 1n the atmosphere.
It Is entirely derived from anthropogenic sources. Its atmospheric lifetime
Is extremely long and almost all the pollutant released has accumulated In
the atmosphere. As with all Inert chemicals that are used as a solvent.
refrigerant or blowing agent, essentially all of the chemical produced will
eventually be released Into the atmosphere. A 7-year monitoring study con-
ducted at seven remote sites around the world reported that concentrations
of I,l.2-tr1chloro-l,2,2-tr1fluoroethane In the atmosphere doubled 1n the
last 5 years. As of September 1988, the background concentration of
I,l,2-tr1chloro-l,2.2-tr1fluoroethane ranged from 40-50 ppt (Khalll and
Rasmussen. 1988). This level appears to Increase 14% each year (Borchers et
al., 1987). The atmospheric concentration of 1.1,2-trlchloro-l.2.2-trl-
fluoroethane In urban and Industrial areas may be much higher as 1,1,2-trl-
chloro-l,2,2-tr1f1uoroethane Is used In consumer products and as an Indus-
trial solvent. The median and maximum concentration of 1,1,2-tr1chloro-
1,2,2-trlfluoroethane at 15 selected urban and suburban sites In the United
States was 170 and 4100 ppt. respectively (Brodzlnsky and Singh, 1982).
v1
-------
Of 79 air samples taken from three urban/Industrial areas of the United
States. 19 were >19 ppb (Plell et al.. 1988).
Many consumer products contain 1.1.2-trlchloro-l,2.2-tr1fluoroethane as.
a solvent. The use of these products will expose the user and bystanders to
1,l,2-tr1chloro-l.2,2-tr1fluoroethane. Exposure will be by Inhalation and
dermal contact with the vapor; It may also be from skin contact with the
liquid solvent. In a 1987 EPA survey of solvents found In household
products, 13% of product categories had one or more brands containing
1.1,2-tr1ch1oro-1.2.2-tr1f1uoroethane (Ueststat and Midwest Research Insti-
tute, 1987). The products most likely to contain 1.1,2-trlchloro-l ,2.2-tM-
fluoroethane were VCR cleaners (71%), video disk cleaners (67%). electric
shaver cleaners (25%) and specialized aerosol cleaners (25%). Many of these
products were entirely or almost entirely composed of 1,1,2-trlchloro-l,2,2-
trlf luoroethane and were not labeled as to their contents.
Since 1.1.2-tr1chloro-l,2,2-tr1f1uoroethane Is used primarily as a
. solvent and Is highly volatile, there Is a potential for exposure In the
workplace. Exposure will be both by Inhalation and dermal contact with the
vapor and liquid solvents. NIOSH (1988) estimated that 134.476 workers.
Including 50.482 women, are exposed to 1.1.2-trlchlorol.2,2-trlfluoroethane
In the workplace. In other NIOSH surveys, an air sample at one company
contained 0.70 ppm of I,l,2-tr1chloro-1,2,2-tr1fluoroethane (Chrostek, 1980)
and personal air samples for workers In another plant contained I,l.2-tr1-
chloro-1,2,2-trlfluoroethane ranging from 0.2-6.7 ppm (Lee and Parkinson.
1982). A worker died and others were overcome while cleaning out a large
vapor degreaser; the concentration of 1.1,2-trlchloro-l,2.2-tr1fluoroethane
may have been as high as 374,000 ppm (Anonymous, 1987). A comprehensive
-------
survey of I,l,2-tr1chloro-l,2,2-tr1fluoroethane levels In occupational atmo-
spheres In France reported that 1.5X of the workplaces had 1,1,2-trlchloro-
l.2,2-tr1fluoroethane of which 10% were between 500 and the TLV value (1000
ppm), and 3% had levels >1000 ppm (Ensmlnger, 1988).
Results of surveys Indicate that the general population may be exposed
to 1,1,2-trlchloro-l,2,2-trlfluoroethane In drinking water derived from
surface and underground sources. 1,1,2-Tr1chloro-l,2,2-tr1fluoroethane has
been found In drinking water In the Great Lakes basin. In a survey In which
nine raw and treated Canadian water supplies were sampled once during each
of three seasons, and a tenth plant was sampled on 5 consecutive days In
each sampling period (Otson. 1987), 1-3 samples contained >0.1 ug/l of7
I,l,2-tr1chloro-l,2,2-trIfluoroethane In raw and treated water and an
additional 1-11 samples contained trace levels of the pollutant. It has
also been found 1n groundwater (1.3 wg/l) near a municipal solid waste
landfill (Sabel and Clark. 1984).
l,l,2-Tr1chloro-l,2,2-trlfluoroethane would tend to partition In air,
rather than In soil and water, because of Us high volatility; therefore. If
I,l,2-tr1chloro-l,2,2-tr1fluoroethane Is found In food. It would most likely
result from air Intake by a plant or animal. 1,1,2-Trlchloro-l ,2,2-tM-
fluoroethane was found In all eight samples of mothers' milk In a pilot
study; the levels were not quantified (PelUzzaM et al., 1982). The
Infants of these mothers would therefore be exposed to 1,1,2-tr1chloro-
1,2,2-tr1fluoroethane In their food.
Pertinent data regarding the environmental toxlclty of 1,2,2-tr1chloro-
1.1,2-trlfluoroethane were not located In the available literature cited In
Appendix A.
-------
Inhalation experiments In humans with '"Cl-labeled 1,1,2-trlchloro-
1.2.2-trlfluoroethane (Morgan et al.. 1972) Indicate that, although pulmo-
nary absorption of 1,l,2-tr1chloro-l,2,2-tr1f1uoroethane occurs, the rate of
absorption 1s lower than that of other chlorinated hydrocarbons such as
trlchloroethane. Dermal absorption has also been shown to occur In humans
(Haskell Laboratory, 1968), but data regarding gastric absorption of
I,l,2-tr1chloro-l,2,2-tr1fluoroethane are not available.
Inhalation studies with- dogs (Trochlmowlcz et al., 1974) and rats
(Carter et al.. 1970; Salvolalnen and Pfaffll. 1980) Indicate that absorbed
I,l,2-tr1chloro-l,2,2-tr1fluoroethane Is rapidly distributed by the blood to
various organs and tissues (Including the brain, liver, adrenal, heart and
thyroid) and Is preferentially deposited Into fat.
Upon cessation of exposure. 1,1.2-tr1ch1oro-1,2,2-tr1fluoroethane Is
rapidly cleared from the body. 1.1,2-Tr1chloro-l,2.2-tr1fluoroethane could
not be detected In the brain, liver, heart, adrenal or thyroid of rats 24
and 48 hours after termination of a 14-day exposure regime, and 1,1,2-trl-
chloro-l,2.2-tr1fluoroethane-levels In fat were decreased by -80 and 99%
during the same respective periods (Carter et al.. 1970).
Human data Indicate that pulmonary exhalation Is a significant excretory
route for 1.1.2-tr1chloro-1.2.2-tr1fluoroethane. 1.1,2-tMchloro-l ,2.2-tM-
fluoroethane was detected In the exhaled air of humans following dermal
administrations of I,l.2-tr1chloro-l,2.2-tr1fluoroethane (Haskell Labora-
tory. 1968).
Identifications have not been made of In vivo metabolites of 1,1,2-trl-
chloro-l,2,2-tr1fluoroethane In animals or humans. Based upon the demon-
stration of \n vitro binding of I.1,2-tr1chloro-l,2.2-tr1f1uoroethane to rat
1x
-------
hepatic cytochrome P-450. a suggestion has been made that 1,1,2-trlchloro-
1.2,2-trlfluoroethane may be oxidized by enzymes associated with P-450
(Valnlo et al.. 1980). but reaction products have not been Identified.
Adverse systemic effects In animals caused by long-term exposure (sub-
chronic or chronic) to vapors of I.l,2-tr1chloro-l,2,2-tr1fluoroethane at
concentrations <2000 ppm have not been Identified, but the data base Is
limited to two rat studies (81 ohm et al., 1985; Trochlmowlcz et al., 1988).
At concentrations >10,000 ppm. adverse body weight changes were observed In
rats (Trochlmowlcz et al., 1988). No adverse changes In body, liver or
kidney weights, liver biochemistry or urinary catecholamlne metabolites were
observed In rats exposed to I,1,2-tr1chloro-l,2,2-tr1f1uoroethane vapors at
concentrations of 200 ppm for 84 days (81 ohm et al., 1985). Chronic
exposure (24 months) of rats to 1,1.2-trlchloro-l,2.2-tr1fluoroethane vapors
'at 2000 ppm caused no adverse changes 1n blood and urine chemical Indices.
body and organ weights or la the histology of major organs and tissues
(Trochlmowlcz et al.. 1988). The same endpolnts were unaffected by higher
chronic exposure levels, except for body weight gain, which was decreased In
both sexes of rats exposed to 20,000 ppm and In female rats exposed to
10,000 ppm.
No adverse effects were Identified In shorter-term studies of dogs.
guinea pigs and rats exposed to vapors of I,l,2-tr1chloro-l,2,2-tr1fluoro-
ethane at concentrations of 5100 ppm for -4 weeks (Steinberg et al.. 1969).
Carter et al. (1970) also reported no adverse effects In Inhalation studies
of monkeys, dogs, mice and rats continuously exposed to 2000 ppm for 14 days.
The only report of I.l.2-tr1chloro-l,2,2-tr1fluoroethane-1nduced
systemic effects other than body weight changes In animals exposed to low to
moderate concentrations comes from a 2-week Inhalation study of rats (Valnlo
-------
et al., 1980). Light microscopy revealed 11p1d accumulation and electron
microscopy revealed changes In the smooth endoplasmlc retlculum In liver
cells from rats exposed to concentrations of 1000 or 2000 ppm. Changes were
also noted In enzymlc activities and reduced glutathlone levels In the liver
of rats exposed to 2000 ppm (Valnlo et al., 1980).
Adverse systemic effects of long-term exposure of humans to vapors of
1,l.2-tr1chloro-l.2.2-tr1fluoroethane have not been clearly Identified. In
a comparison of chronically exposed human workers with unexposed workers
(Imbus and Adklns, 1972), no adverse effects were noted In physical examina-
tions of workers who worked an average 2.8 years In rooms In which average
concentrations of 1,l.2-tr1ch1oro-l,2.2-tr1fluoroethane were estimated to be
699 ppm. Eplderalologlcal and case-report studies suggest, however, that
long-term occupational exposure to vapors of I.l,2-tr1chloro-l.2,2-tr1-
fluoroethane may cause neuropsychologlcal effects (Rasmussen and Sabroe,
1986; Rasmussen et al.. 1988J or neuropathy (Raffl and Vlolante. 1981).
Further Information Is needed to substantiate the suggestions of the
epldemlologlcal and case-report studies.
•
Acute exposures (<2 hours) to moderate concentrations (>2500 ppm) of
•
I,l,2-tr1chloro-l,2.2-tr1fluoroethane vapors altered the performance of
volunteers In psychophyslologlcal tests (Stopps and Mclaughlin, 1967).
Exposure of human volunteers to lower concentrations (<1QOO ppm) for a
longer duration (6 hours/day. 5 days/week for 2 weeks) did not cause
treatment-related changes In performance In psychophyslologlcal tests or In
physical examinations (Relnhardt et al., 1971b);
The acute lethality of 1,1,2-trlchloro-l,2,2-trlfluoroethane 1s low when
administered to animals by either oral or Inhalation routes. An oral LD50
of 43 g/kg was determined for rats (Michaelson and Huntsman. 1964), but
x1
-------
rabbits appeared more susceptible. Half of a group of eight rabbits died
after receiving one to four doses of 5 g/kg/day (Busey et al., 1967).
Two-hour LC5Q values of 95,000, 120,000 and 110,000 ppm were determined
for Inhalation exposures of mice, guinea pigs and rats, respectively
(Desollle et al.,1968).
Acute exposures to moderate to high concentrations of 1,1,2-trlchloro-
1,2,2-trlfluoroethane caused CNS effects In two animal species. Reversible
CNS effects were seen In dogs and rats given 6-hour exposures to
11,000-13,000 ppm (Steinberg et al., 1969), and an EC5Q value of 28,000
ppm was determined for CNS effects In rats given I0-m1nute exposures (.Clark
and Tlnston, 1982). The mechanistic connection between these CNS effects
and the observation of minor biochemical effects In brain preparations from
rats exposed to concentrations <2000 ppm for 2 weeks (Savolalnen and
Pfaffll, 1980) currently Is unclear.
Accidental and voluntary human exposures to high concentrations of
. I,l,2-tr1chloro-l,2,2-tr1fluoroethane vapors caused sudden death generally
thought to be due to cardiac arrest (Hay and Blotzer, 1984; Relnhardt et
al.. 1971a. 1973; Zakharl and Avlado. 1982). This hypothesis has received
support from animal studies In which acute exposures (5-10 minutes) to
moderate to high concentrations caused adverse cardiac effects. Cardiac
sensltlzatlon to eplnephrlne-lnduced arrhythmias was observed In dogs at
concentrations >5000 ppm (Relnhardt et al. 1973) and In anesthetized mice at
concentrations >50,000 ppm (Avlado and BeleJ, 1974). An EC.- for cardiac
sensltlzatlon of 10,000 ppm was determined for 5-m1nute exposures of dogs
(Clark and Tlnston, 1973). In anesthetized rhesus monkeys, 5-mlnute
exposures to concentrations >25,000 ppm caused arrhythmias, myocardlal
depressions and tachycardia, without administration of exogenous eplnephrlne
(BeleJ et al., 1974).
-------
Acute 5-minute exposures to vapors of I.l,2-tr1chloro-l.2,2-tr1fluoro-
ethane at concentrations >25,000 ppm altered pulmonary function In rhesus
monkeys (Avlado and Smith, 1975). In. vitro experiments with excised rat
lungs (Alarle et al.. 1975) Indicated that this effect may Involve Inter-
action of I,1.2-tr1ch1oro-l,2.2-tr1fluoroethane with surfactant on the Inner
alveolar surface.
Perltlnent data regarding the systemic toxldty of chronic or subchronlc
exposure to orally administered 1,1,2-trlch1oro-l,2t2-tr1f1uoroethane were
not located In the available literature cited In Appendix A.
Data regarding the carclnogenlclty of I.l,2-tr1chloro-l.2,2-tr1flupro-
ethane are limited to a 2-year Inhalation study In which rats were exposed
to concentrations of 0, 2000, 10,000 or 20,000 ppm (Troch1mow1cz et al.,
1988). No treatment-related Increases In tumor Incidences were reported.
1.1,2-tr1ch1oro-l.2,2-tr1fluoroethane was not mutagenlc In assays for
dominant lethal mutations In mice (Epstein et al., 1972) nor In assays for
reverse mutations In Salmonella typhlmurlura (Simmon et al., 1977; Longstaff,
1988; Hahurln and Bernstein. 1988).
The U.S. EPA (1983) summarized three unpublished studies (Ward, 1983;
Hazelton Laboratories. 1967a,b), which contain the only available data
regarding the teratogenldty and other reproductive effects of 1,1,2-trl-
chloro-l,2,2-tr1fluoroethane. The summarized data Indicate that 1,1,2-tM-
chloro-1,2,2-tMfluoroethane was not teratogenlc In rats exposed to air
containing <25,000 ppn on days 6-15 of gestation (Hard, 1983), but conclu-
sions were precluded 1n rabbit studies (Hazelton Laboratories. 1967a,b)
•
because of marked maternal toxlclty and Inadequate numbers of animals.
l,l.2-Tr1chloro-l,2,2-tr1fluoroethane Is assigned to EPA Group 0 (not
classifiable as to carclnogenlclty to humans) because no human data are
-------
available and negative data are available for only one animal species —
rats (Trochlmowlcz et a!.. 1988). Therefore, neither quantitative estimates
of cancer risks (q,*s) nor a cancer-based RQ were derived.
An RfO of 27 mg/ma for chronic Inhalation exposure was derived from a
LOAEL of 2000 ppm, 6 hours/day, 5 days/week for decreased body weight In
female rats relative to controls In the 24-month study by Trochlmowlcz et
al. (1988). Confidence In the Inhalation RfO Is medium reflecting the high
quality of the key study but the Inadequacy of supporting Information
regarding the reproductive and teratogenlc effects of Inhaled 1,1,2-trl-
ch1oro-l,2,2-trlfluoroethane. Because of a limited data base for subchronlc
Inhalation exposure, the chronic Inhalation RfO was also adopted as the RfD
for subchronlc exposure.
An oral RfD of 3 mg/kg/day for either subchronlc or chronic oral
exposure was derived from the chronic Inhalation RfO. because of a lack of
data regarding oral exposures to 1.1,2-tr1chloro-l,2,2-tr1fluoroethane.
Confidence In the oral RfO 1s low because of the uncertainty of route-to-
route .extrapolation. An RQ of 5000 based on chronic Inhalation toxlclty was
also derived for decreased body weights In female rats (Trochlmowlcz et al..
1988).
xlv
-------
TABLE OF CONTENTS
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
1.3. PRODUCTION DATA 2
1.4. USE DATA 4
1.5. SUMMARY 4
2. ENVIRONMENTAL FATE AND TRANSPORT 5
2.1. AIR 5
2.2. WATER 6
2.3. SOIL 7
2.4. SUMMARY 8
3. EXPOSURE 11
3.1. WATER 11
3.2. FOOD 11
3.3. INHALATION 12
3.4. DERMAL 14
3.5. SUMMARY 15
4. ENVIRONMENTAL TOXICOLOGY 18
4.1. AQUATIC TOXICOLOGY 18
4.1.1. Acute Toxic Effects on Fauna 18
4.1.2. Chronic Effects on Fauna 18
4.1.3. Effects on Flora 18
4.1.4. Effects on Bacteria 18
4.2. TERRESTRIAL TOXICOLOGY 18
4.2.1. Effects on Fauna 18
4.2.2. Effects on Flora 19
4.3. FIELD STUDIES 19
4.4. AQUATIC RISK ASSESSMENT 19
4.5. SUMMARY 19
5. PHARHACOKINETCS 20
5.1. ABSORPTION 20
5.2. DISTRIBUTION I 23
5.3. METABOLISM 25
5.4. EXCRETION 26
5.5. SUMMARY 26
xv
-------
TABLE OF CONTENTS (cont.)
Page
6. EFFECTS 28
6.1. SYSTEMIC TOXICITY 28
6.1.1. Inhalation Exposure 28
6.1.2. Oral Exposure 31
6.1.3. Other Relevant Information 31
6.2. CARCINOGENICITY 36
6.2.1. Inhalation 36
6.2.2. Oral 37
6.2.3. Other Relevant Information 37
6.3. MUTAGENICITY 39
6.4. DEVELOPMENTAL TOXICITY 39
6.5. OTHER REPRODUCTIVE EFFECTS 41
6.6. SUMMARY 41
7. EXISTING GUIDELINES AND STANDARDS 46
7.1. HUMAN : . . . 46
7.2. AQUATIC 47
8. RISK ASSESSMENT 48
8.1. CARCINOGENICITY 48
8.1.1. Inhalation 48
8.1.2. Oral 48
8.1.3. Other Routes 48
8.1.4. Weight of Evidence 48
8.1.5. Quantitative Risk Estimates 49
8.2. SYSTEMIC TOXICITY 49
8.2.1. Inhalation Exposure 49
8.2.2. Oral Exposure 52
9. REPORTABLE QUANTITIES 54
9.1. BASED ON SYSTEMIC TOXICITY 54
9.2. BASED ON CARCINOGENICITY '. 54
10. REFERENCES 58
APPENDIX A: LITERATURE SEARCHED 72
APPENDIX B: SUMMARY TABLE FOR 1,1,2-TRICHLORO-l,2,2-TRIFLUOROETHANE. . 75
APPENDIX C: DOSE/DURATION RESPONSE GRAPH(S) FOR EXPOSURE TO
1.1,2-TRICHLORO-1,2.2-TRIFLUOROETHANE 76
xvl
-------
LIST OF TABLES
No.
1-1
5-1
6-1
6-2
9-1
9-2
9-3
Title
Manufacturers of 1 ,1,2-TMchloro-l, 2, 2-tr1f luoroethane \n
the United States as of January, 1987
Tissue Concentrations of l.l,2-Tr1chloro-l,2,2-trlfluoro-
ethane from Rats Exposed to Air Containing 2000 ppm
Incidence of Tumors In Crl :C08R Rats Exposed to Vapors of
1.1,2-TMchloro-l. 2. 2-tr1f luoroethane for 24 Months
Mutagenlcity Testing of l.l,2-Tr1chloro-1.2,2-Tr1-
fluoroethane
Inhalation Tox1c1ty Summary for 1,1 ,2-Tr1chloro-l ,2,2-
Tr If luoroethane
Inhalation Composite Score for 1 ,1 ,2-Trlchloro-l ,2,2-
Tr 1 f luoroethane
1, 1,2-Tr1chloro-l, 2, 2-Trlf luoroethane: Minimum Effective
Dose (MED) and Reoor table Quantity (RO)
Page
3
24
38
40
55
56
57
XV11
-------
LIST OF ABBREVIATIONS
AEL Adverse effects level
BCF B1oconcentrat1on factor
BUN Blood urea nitrogen
CAS Chemical Abstract Service
CNS Central nervous system
CS Composite score
CT Computerized tomography
EC5Q Concentration effective to SOX of recipients
(and all other subscripted concentration levels)
FEL Frank effect level
HEC Human equivalent concentration
Koc Soil sorptlon coefficient standardized
with respect to organic carbons
K Octanol/water partition coefficient
LC5Q Concentration lethal to 50% of recipients
(and all other subscripted dose levels)
LD,- Dose lethal to 50% of recipients
LOAEL Lowest-observed-adverse-effect level
NAOPH Nlcotlnamlde adenlne dlnucleotlde phosphate
(reduced form)
NOEL No-observed-effect level
ppb Parts per billion
ppm Parts per million
ppt Parts per trillion
RfO Reference dose
RNA Rlbonuclelc add
RV. Dose-rating value
RVe Effect-rating value
STEL Short-term exposure level
TLV Threshold limit value
TWA Time-weighted average
UOP UMdlne dlphosphate
UV Ultraviolet
XV111
-------
1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
1,1,2-Trlchloro-l,2,2-trlfluoroethane Is the chemical name of the
compound commonly known as Freon 113. Other synonyms and trade names for
this chemical are 1.1,2-trlchlorotrlfluoroethane. Freon TF, Genetron 113,
R113, Uncon Fluorocarbon 113, Arklone P, FMgen A, TR-T and trlchlorotrl-
fluoroethane (Chemllne, 1989). The molecular structure, molecular weight,
empirical formula and CAS Registry number for I,l,2-tr1chloro-l,2,2-tr1-
fluoroethane are as follows:
Molecular structure: CC12F-CC1F2
Molecular weight: 187.38
Empirical formula: CjCI-jFj
CAS Registry number: 76-13-1
1.2. PHYSICAL AND CHEMICAL PROPERTIES
l,l,2-Tr1chloro-1,2,2-tr1f1uoroethane Is a colorless, volatile liquid
(Hawley, 1981). It has a sweet odor and Is noncombustlble (Hawley, 1981;
Verschueren, 1983). Selected physical properties are listed below:
Boiling point: 47.57'C Smart. 1980
46'C Parrlsh, 1983
Melting point: -35'C Smart, 1980
-36-C Parrlsh, 1983
Density (g/mt) (250C): 1.565 Smart, 1980
1.56354 Parrlsh, 1983
Vapor pressure
at 20"C: 270 mm Hg . Verschueren, 1983
at 25'C: 330 mm Hg Parrlsh, 1983
at 30-C: 400 mm Hg Verschueren, 1983
Vapor density: 6.47 Verschueren, 1983
Flash point: not available
0275d -1- 11/15/89
-------
Water solubility (2S*C): 0.017 wt % Smart. 1980
0.01664 wt X Horvath, 1982
Log Kou: 3.16 McOuffle. 1981
3.29 (estimated) U.S. EPA. 1987
Air odor threshold: 45 ppm Amoore and Hautala, 1983
Air conversion factor: 1 mg/m3 - 0.13 ppm
1 ppm « 7.69 mq/m3
1.3. PRODUCTION DATA
l,l,2-Tr1ch1oro-l,2,2-tr1fluoroethane 1s manufactured by reacting
hexachloroethane with hydrogen fluoride In the presence of a chromium oxide
or hallde, ferric chloride or thorium tetrafluorlde catalyst (Smart, 1980).
In this process, the chlorine atoms.are successively replaced by fluorine
atoms; the extent of replacement Is controlled by varying the concentration
of hydrogen fluoride, the reaction time and temperature. The companies
currently producing 1.1,2-trlchloro-l,2.2-trIfluoroethane 1n the United
States are shown In Table .1-1. No production data are available. The
amount of 1,1,2-trlchloro-1,2,2-trlfluoroethane emitted Into the atmosphere
annually has Increased sharply since It was first used commercially around
1960; the annual emission leveled off In 1980 and was estimated as 97
klloton/year (88 million kg/year) during 1980-1983 (Borchers et al.. 1987).
This results In an annual Increase of -15X per year. By applying the
results of 7 years of monitoring data of 1,1,2-trlchloro-l,2.2-trlfluoro-
ethane to a mass balance model, another Investigator estimated that
emissions over the time period September 1982-September 1988 were 100
million kg/year and were Increasing exponentially at 5X per year (Khalll and
Rasmussen, 1988).
0275d -2- 11/15/89
-------
TABLE 1-1
Manufacturers of l,l,2-Tr1chloro-l,2,2-tr1fluoroethane In the
United States as of January. 1987*
Manufacturer
Location
Allied Signal. Inc.
E.I. du Pont de Nemours & Co.. Inc.
Penwalt Corporation
Baton Rouge. LA
Corpus Chrlstl, TX
Montague. MI
NA
•Source: SRI. 1988; USITC. 1988
NA » Not available
0275d
-3-
11/15/89
-------
1.4. USE DATA
Since 1960, 1,1,2-tr1chloro-l,2,2-tr1Muoroethane has been used
primarily as a solvent, although 1t can also be used as a blowing agent and
refrigerant (Borchers et al., 1987). Its use as a dry cleaning agent Is
limited because of Its expense (ParMsh, 1983).
1.5. SUMMARY
l,l.2-Tr1chloro-l.2.2-tr1fluoroethane Is a colorless, volatile liquid
with a sweet odor (Hawley. 1981; Verschueren, 1983). 1,1,2-TMchloro-l,2,2-
tMfluoroethane 1s manufactured by reacting hexachloroethane with hydrogen
fluoride In the presence of a catalyst (Smart. 1980). The extent of
chlorine atom replacement 1s controlled by varying the concentration of
hydrogen fluoride and the reaction time and temperature. No production data
are available. It Is used primarily as a solvent (Borchers et al.. 1987).
0275d -4- 11/15/89
-------
2. ENVIRONMENTAL FATE AND TRANSPORT
2.1. AIR
l,l,2-Tr1chloro-l,2,2-tr1fluoroethane Is extremely stable In the tropo-
sphere (Borchers et al., 1987). It does not adsorb UV radiation >290 nm
(Hubrlch and Stahl, 1980) and It will not directly photolyze (Haklde et al..
1979). It does not react with photochemically produced hydroxyl radicals
(Atkinson, 1985). It will therefore disperse over the globe and diffuse
slowly Into the stratosphere where It will be photolyzed by the short wave
length UV radiation and 0(10) attack (Borchers et al., 1987). Over 80% of
the I,l,2-tr1ch1oro-l,2.2-tr1fluoroethane In the stratosphere Is estimated
to be removed by photolysis (Chou et al.. 1978). Chlorine radicals
generated In the photolysis are responsible for the destruction of the
stratospheric ozone layer. An Intensive 7-year study monitored 1,1,2-trl-
chloro-1,2.2-tr1fluoroethane weekly at seven locations ranging from the
arctic to the antarctic regions. The data applied to a global mass balance
equation resulted In a half-life of 48.5 years (Khalll and Rasmussen, 1988).
Previous estimated half-lives for 1.1.2-tr1chloro-1.2.2-tr1fluoroethane In
the atmosphere range from 44-85 years (Chou et al.. 1978); therefore, the
1,1,2-trkhloro-l,2,2-trlfluoroethane released to the atmosphere would be
expected to accumulate and Us concentration In air would be fairly uniform
over the globe. Its concentration will decrease sharply with altitude as It
reaches the stratosphere (Borchers et al., 1987; Fabian, 1986).
l,l,2-Tr1chloro-l,2,2-tr1fluoroethane will also be removed from the
atmosphere by dry and wet deposition; however, the 1,l.2-tr1chloro-l,2,2-
tMfluoroethane removed In this manner will volatilize back Into the
atmosphere.
0275d -5- 11/15/89
-------
2.2. HATER
The fate of I,1,2-tr1ch1oro-l,2,2-tr1fluoroethane 1n water depends on
Us transport, not Us degradation. 1,1.2-Trlchloro-l.2,2-tr1fluoroethane
has a very high vapor pressure, 330 mm Hg at 25'C (Parrlsh, 1983), and low
solubility In water, 170 mg/l (Smart, 1980). The Henry's Law constant for
I,l,2-tr1ch1oro-l,2.2-tr1fluoroethane calculated from Us vapor pressure and
water solubility Is 0.48 atm-mVmol; therefore. Us volatilization from
water will be rapid. The volatilization rate will be controlled by Us
diffusion through water. The half-life of I,l,2-tr1chloro-1,2,2-tr1fluoro-
ethane In a model river 1 m deep, flowing at 1 m/sec, with a wind of 3 m/sec
Is estimated to be 4.0 hours (Thomas, 1982). Experimental data regarding
the adsorption of 1,1.2-trlchloro-l,2.2-tr1fluoroethane to sediment and
suspended solids In the water column were not found In the available litera-
ture. Based on Us water solubility. 170 mg/l at 25'C (Smart. 1980), a
KQC of 426 was estimated using a regression equation based on chlorinated
hydrocarbons, log KQC • -0.557 log S «• 4.277 (S 1n jimol/l) (Chlou et
al., 1979; Lyman, 1982). Therefore, 1 ,l,2-tr1chloro-l.2.2-tr1fluoroethane
would probably adsorb moderately to sediment and suspended solids In the
•
water column.
Fluorocarbons are chemically Inert under environmental conditions
(Council on Environmental Quality. 1975). Under environmental conditions.
alkyl fluorides are likely to hydrolyze too slowly for this pathway to be
significant (Rabey and mil. 1978). The reactivity of fluorlnated alkanes
decreases as the fluorine content of the molecule Increases (Smart. 1980).
The rate of hydrolysis of I,l,2-tr1chloro-1.2'.2-tr1fluoroethane Is very low.
(<0.005 g/i-yr) at 30*C. (Du Pont de Nemours Co.. 1980). Fluorocarbons
are highly resistant to attack by oxidizing agents under environmental
0275d -6- 11/15/89
-------
conditions (Howard et al.. 1975). Lacking any UV absorption >290 nm
(Hubrlch and Stahl. 1980). direct photolysis should not be significant. Its
Inertness to photooxldatlon Is Illustrated by Us use as a solvent for
determining the photooxldatlon of organic compounds by hydroxyl radicals
(Dllllng et al., 1988). While no Information was found concerning the
blodegradatlon of I,l,2-tr1chloro-l,2.2-trlfluoroethane, Us rapid volatili-
zation would limit, If not preclude, blodegradatlon (Howard et al.. 1975).
No experimental data were found regarding the bloconcentratlon of 1,1.2-tM-
chloro-l.2,2-tr1fluoroethane In fish and aquatic organlcs. No reports
concerning Us detection In fish were located. Based on Us log K
ow
determined by high pressure liquid chromatography to be 3.16 (HcOuffle,
1981), a BCF of 148 may be estimated from the equation log BCF * 0.76 log
KOW 0.23 (Bysshe, 1982). ' This Indicates that 1.1.2-tr1chloro-l,2.2-tr1-
fluoroethane should have a fairly low potential for bloconcentratlng In
aquatic organisms.
2.3. SOIL
Pertinent data regarding the adsorption of I.l.2-tr1ch1oro-l.2.2-tr1-
fluoroethane to soil were not located In the literature cited In Appendix A.
Its estimated K of 426 (see Section 2.1.) would Indicate a medium
potential for leaching Into groundwater (Swann et al.. 1983). To ascertain
Its leaching potential from landfills, columns of domestic waste contami-
nated with 1,1,2-tr1chloro-1,2,2-tr1fluoroethane and other halogenated
organic solvents were eluted with water (Jones et al., 1978). The concen-
tration of the I,l,2-tr1ch1oro-1,2,2-tr1fluoroethane was at least 2 orders
of magnitude lower than In the solid waste, suggesting that evaporation and
possibly adsorption effectively reduces the solvent leached from landfills.
0275d -7- 11/15/89
-------
It has been reported In contaminated groundwater near a municipal solid
waste landfill (Sabel and Clark. 1984). Because of Us very high vapor
pressure, very high Henry's Law constant and moderate adsorption to soil.
1,1,2-trlchloro-l ,2,2-tMfluoroethane would be expected to volatilize
rapidly from both dry and moist soil.
Pertinent data regarding the fate of 1,1,2-tr1chloro-l,2,2-tr1fluoro-
ethane In soil as a result of mlcroblal or chemical reactions or Interaction
with sunlight were not located In the available literature cited In Appendix
A. Based on Its very high volatility and general unreactlvHy, It Is
unlikely that photooxldatlon, hydrolysis or blodegradatlon will be signifi-
cant In soil.
2.4. SUMMARY
The key factors affecting the fate of I,l.2-tr1chloro-l.2.2-trlfluoro-
ethane 1n the environment are Us very high vapor pressure, combined with
Us low solubility In water and chemical Inertness. The Henry's Law
constant for 1,1.2-trlchloro-l,2,2-tr1fluoroethane calculated from Us vapor
pressure. 330 mm Hg at 25*C (Parrlsh. 1983). and water solubility. 170
mg/l (Smart. 1980). Is 0.48 atm-m»/mo1. Therefore. Us volatilization
from water will be very rapid, with the volatilization rate limited by Us
diffusion through water. The half-life of 1,l.2-tr1ch1oro-l,2.2-trlfluoro-
ethane 1n a model river 1 m deep, flowing at 1 m/sec. with a wind of 3 m/sec
Is estimated to be 4.0 hours (Thomas. 1982). Experimental data regarding
the adsorption of 1,1,2-trlchloro-l,2,2-trlfluoroethane to soil, sediment
and suspended solids In the water column were not located In the available
literature, and a KQC of 426 was estimated from Us water solubility (see
Section 2.1.). This moderate KQC Indicates that adsorption to sediment
and partlculate matter In the water column would not compete effectively
0275d -8- 11/15/89
-------
with volatilization from water. Because of I,l,2-tr1chloro-l,2,2-trlfluoro-
ethane's high vapor pressure, high Henry's Law constant and moderate adsorp-
tion to soil, 1,1,2-trlchloro-l,2,2-trlfluoroethane would also be expected
to volatilize rapidly from both dry and moist soil. Its K of 426 would
Indicate a moderate potential for leaching Into groundwater (Swann et al.,
1983).
Pertinent data regarding the fate of I,l,2-tr1chloro-l,2,2-tr1fluoro-
ethane In water or soil as a result of microblal or chemical reactions or
Interaction with sunlight were not located In the available literature cited
In Appendix A. Under environmental conditions, alky! fluorides are likely
'.to hydrolyze too slowly for this pathway to be significant (Nabey and Hill,
1978). Fluorocarbons are highly resistant to attack by oxidizing agents
under environmental conditions (Howard et al.. 1975). Lacking any UV
absorption >290 nm (HubMch and Stahl. 1980), direct photolysis should not
be significant. While no Information was found concerning the blodegrada-
tlon of I,l,2-tr1chloro-l,2,2-tr1fluoroethane. Us rapid volatilization
would limit, If not preclude, blodegradatlon (Howard et al.. 1975); there-
fore. It Is unlikely that photooxldatlon. hydrolysis or blodegradatlon will
be significant In water or soil.
Pertinent data regarding the bloconcentratlon of 1.1,2-tr1chloro-l,2,2-
trlfluoroethane In fish and aquatic organisms were not located In the
available literature. The estimated 8CF. 148 (see Section 2.1.), Indicates
that I,l,2-tr1chloro-1,2,2-tr1fluoroethane should have a low potential for
bloconcentratlng In aquatic organisms.
As a result of Its high volatility, T.I,2-tr1chloro-l,2,2-trlfluoro-
ethane will partition Into air. 1,l,2-Tr1chloro-l,2,2-tr1fluoroethane Is
extremely stable In the troposphere (Borchers et al.. 1987); U will not
directly photolyze or react with photochemically produced hydroxyl radicals.
0275d -9- 11/15/89
-------
It Mill disperse over the globe and diffuse slowly Into the stratosphere.
where It will be destroyed by photolysis by short wave length UV radiation
and. to a lesser degree, by 0(1D) attack (Botchers et al., 1987). An
Intensive 7-year study monitored 1.1,2-tr1chloro-l,2.2-tr1fluoroethane
weekly at seven locations ranging from the arctic to the antarctic regions.
The data applied to a global mass balance equation resulted In a half-life
of 48.5 years (Khali! and Rasmussen, 1988). Therefore, the 1,1,2-trlchloro-
1.2,2-trlfluoroethane released to air would be expected to accumulate there.
Its concentration In the atmosphere, removed from local sources, would be
fairly uniform over the world. 1.1.2-Tr1chloro-l,2.2-tr1fluoroethane will
be removed from the atmosphere by dry and wet deposition and will return to
the atmosphere by volatilization.
0275d -10- 11/15/89
-------
3. EXPOSURE
3.1. HATER
A study was conducted to determine the levels of selected volatile
pollutants In raw and treated drinking water along a portion of the Great
Lakes basin. Nine raw and treated Canadian water supplies were sampled once
during summer, 1982; winter, 1983; and spring. 1983. A tenth plant was
sampled on 5 consecutive days In each period (Otson, 1987). In all time
periods, 1-3 of the 14 samples contained >0.1 yg/i of 1,1,2-trlchloro-
1,2,2-tMfluoroethane 1n raw and treated water. An additional 1-11 samples
contained trace levels of the pollutant. In all cases, the mean value of
I,l,2-tr1chloro-l,2,2-tr1fluoroethane was <0.1 yg/i. Another study of
the Great Lakes basin found 1,1,2-tMchloro-l,2.2-tMfluoroethane 1n water
samples taken from the Niagara River (Lake Ontario basin) and Cayuhoga River
(Lake Erie Basin}, but not the western section of Lake Ontario (Great Lakes
Hater Quality Board, 1983). No concentration levels were reported. In a
survey of leaching from municipal solid waste landfills In Minnesota,
1,1,2-trlchloro-l ,2,2-trlfluoroethane was found In 1 of 13 grouridwater
samples at a concentration of 1.3 vg/t (Sabel and Clark, 1984).
l,l,2-TMchloro-l,2,2-tr1fluoroethane has been found at 8 of 1177 hazardous
waste sites listed on the National Priorities List (MITRE. 1988). It could
leach from these landfills Into groundwater. These studies Indicate that
the general population may be exposed to 1,1,2-tr1chloro-l,2,2-trlfluoro-
ethane In water.
3.2. FOOD
l,l,2-Tr1chloro-l,2,2-tr1fluoroethane would tend to partition In air,
rather than soil and water, because of Us high volatility; therefore, If
I.l,2-tr1chloro-l,2,2-tr1fluoroethane occurs 1n food. It would most likely
0275d -11- 11/15/89
-------
result From air Intake by a plant or animal. A pilot study of volatile
organic chemicals In mothers' milk found that all eight samples of milk
obtained from women In four urban areas In the United States contained
I,l,2-tr1chloro-1.2,2-tr1f1uoroethane; the levels were not quantified
(PelUzzaM, 1982). The Infants of these mothers would therefore be exposed
to I,l,2-tr1chloro-l.2.2-tr1fluoroethane In their food. No other data were
located In the available literature In which 1,l,2-tr1chloro-l.2.2-tM-
fluoroethane was found In food.
3.3. INHALATION
l,1,2-Tr1chloro-l,2,2-tr1f1uoroethane found In the atmosphere originates
entirely from anthropogenic sources. Since Its atmospheric lifetime Is
extremely long, almost all the pollutant released has accumulated In the
atmosphere. A 7-year monitoring study conducted at seven remote sites
around the world reported that the concentration of I,l,2-tr1chloro-l,2.2-
trlfluoroethane In the atmosphere has doubled In the last 5 years. As of
September 1988, the concentration ranged from 40-50 ppt (Khalll and
Rasmus sen, 1988). An analysis of data collected In 2 years of monitoring at
Barrows, AK, Indicates that the level of 1,l,2-tr1ch1oro-1.2,2-tr1fluoro-
ethane In the atmosphere 1s Increasing 14% each year (Borchers et al.,
1987); therefore, we are exposed to 1 ,l,2-tr1chloro-l,2,2-tr1fluoroethane In
air all over the world.
The median concentration of I,l,2-tr1chloro-l,2,2-tr1fluoroethane at six
selected rural and remote sites and 15 selected urban and suburban sites In
the United States was 31 and 170 ppt. respectively (Brodzlnsky and Singh,
1982). The maximum concentration reported In urban/suburban sites was 4100
ppt. The data summarized In this survey came from a number of studies and
spanned many years. Assuming an air concentration of 31 and 170 ppt In
0275d -12- n/i5/89
-------
rural and urban areas and an air Intake of 20 m3. a person would breathe
In 4.8 and 26 vq of 1,1,2-tr1chloro-l,2,2-trlfluoroethane dally. Of 79
air samples taken from the Kanawana Valley. HV (March, 1986). Los Angeles.
CA (August, 1986) and Houston. TX (August. 1986 to March. 1987). 60 were <1
ppb (mean value of 0.27 ppb) and 19 were >1 ppb (mean 6.69 ppb) (Plell et
al., 1988).
In 1987, the results of an EPA survey of solvents found In household
products was published (Weststat. Inc. and Midwest Research Institute,
1987). In the survey, various brands of products In 82 product categories
were analyzed. Of these. 67 contained solvents and 11 of these product
categories had one or more brands containing 1,1,2-trlchloro-l,2,2-trl-
fluoroethane. The products most likely to contain 1.1.2-tr1ch1oro-l,2,2-
trlfluoroethane were VCR cleaners (71X), video disk cleaners (67%), electric
shaver cleaners (25X) and specialIzed'aerosol cleaners (25X). Many of these
products were entirely or almost entirely composed of 1.1,2-tr1chloro-l,2,2-
trlfluoroethane and were not labeled as to their contents. Any volatile
solvent will expose people In the vicinity to the compound unless extreme
precautions are taken. No concentration levels of 1,1,2-tr1chloro-l,2,2-
trlfluoroethane In homes where products containing 1,1,2-trlchloro-l,2,2-
trlfluoroethane were found In the available literature.
Since I,l.2-tr1chloro-l.2.2-tr1fluoroethane Is used primarily as a
solvent and Is highly volatile, there Is a great potential for exposure In
the workplace. According to statistical estimates, 134,476 workers, Includ-
ing 50,482 women, are exposed to I.l,2-tr1chloro-1,2,2-trIfluoroethane 1n
the workplace (NIOSH. 1988). The National' Occupational Exposure Survey
(NOES) was based on field surveys of 4490 facilities and designed as a
nationwide survey based on a statistical sample of virtually all workplace
0275d -13- 11/15/89
-------
environments \n the United States where eight or more persons are employed
1n all standard Industrial codes except mining and agriculture. A German
survey conducted from 1978-1982 of organic solvents present in 275 products
commonly found In the workplace reported that 1.5X of these products
contained I,l,2-tr1chloro-l,2,2-tr1fluoroethane {Lehmann et al., 1986).
1.1.2-Tr1chloro-1.2.2-trlfluoroethane was monitored In several health
hazard evaluations conducted by NIOSH. An air sample at the Fischer and
Porter Company In Warmlnster, PA. contained 5.4 mg/ra" (0.70 ppm) of
I,1.2-trlchloro-1.2,2-tr1f1uoroethane (Chrostek, 1980). 1.1.2-trlchloro-
l.2.2-tr1fluoroethane was used as a degreaser In the plant. Personal air
samples for workers In a plant In Pennsylvania that manufactured automobile
speakers ranged from 0.2-6.7 ppm (Lee and Parkinson. 1982). A worker died
and others were overcome while cleaning out a large vapor degreaser at a
chemical fuel plant (Anonymous. 1987). The decreasing tank had been drained
of all the solvent except for 1 gallon. The concentration of I,l,2-tr1-
ch1oro-1.2.2-tr1fluoroethane may have been as high as 374.000 ppm.
Ensrolnger (1988) sampled organic solvents In 543 workplaces In France
from 1981-1985. Of the 2013 samples. 30 contained 1.1.2-tr1chloro-l,2.2-
trlfluoroethane as follows: 43.5X were <10% of the TLV, 43.5X were >10X and
<50X of the TLV. 10% were >50% and <100X of the TLV and 3X were >100% of the
TLV. The ACGIH TLV Is 1000 ppm (Lee and Parkinson. 1982).
3.4. DERMAL
Consumers and workers who use solvents containing I,l,2-tr1chloro-l,2,2-
tMfluoroethane may be dermally exposed to this chemical. Exposure may be
•
from direct skin contact with the liquid solvent or from contact with vapors
and aerosols.
0275d -14- 11/15/89
-------
3.5. SUMMARY
1.1.2-TMchloro-l.2,2-tr1f luoroethane Is ubiquitous In the atmosphere.
It Is entirely derived from anthropogenic sources. Its atmospheric lifetime
Is extremely long and almost all the pollutant released has accumulated In
the atmosphere. As with all Inert chemicals that are used as a solvent,
refrigerant or blowing agent, essentially all of the chemical produced will
eventually be released Into the atmosphere. A 7-year monitoring study
conducted at seven remote sites around the world reported that concentra-
tions of I,l,2-tr1chloro-l,2,2-tr1fluoroethane In the atmosphere doubled In
the last 5 years. As of September 1988. the background concentration of
•i
1,1,2-trlchloro-l,2,2-trlfluoroethane ranged from 40-50 ppt (Khalll and
Rasmussen. 1988). This level appears to Increase 14% each year (Borchers et
al., 1987). The atmospheric concentration of I.l,2-tr1chloro-l,2.2-tr1-
fluoroethane In urban and Industrial areas may be much higher as 1,1,2-trl-
chloro-l ,2,2-tr1f luoroethane Is used In consumer products and as an Indus-
trial solvent. The median and maximum concentration of 1,1,2-trlchloro-
1.2,2-trifluoroethane at 15 selected urban and suburban sites In the United
States was 170 and 4100 ppt, respectively (Brodzlnsky and Singh. 1982). Of
79 air samples taken from three urban/Industrial areas of the United States,
19 were >19 ppb (Plell et al., 1988).
Many consumer products contain 1,1,2-tr1chloro-l.2,2-trlfluoroethane as
a solvent. The use of these products will expose the user and people nearby
to 1.1.2-trlchloro-l,2,2-tr1fluoroethane. Exposure will be by Inhalation
and dermal contact with the vapor; 1t may also be from skin contact with the
liquid solvent. In a 1987 EPA survey of solvents found In household
products, 13X of product categories had one or more brands containing
1.1.2-trlchloro-l,2.2-tr1fluoroethane (Weststat. Inc. and Midwest Research
Q275d -15- 11/15/89
-------
Institute, 1987). The products most likely to contain 1.1.2-trlchloro-
1,2,2-tMfluoroethane were VCR cleaners (71%). video disk cleaners (67%),
electric shaver cleaners (25X) and specialized aerosol cleaners (25X). Many
of these products were entirely or almost entirely composed of 1,1,2-trl-
chloro-l,2,2-tr1fluoroethane and not labeled as to their contents.
Since I,l,2-tr1chloro-l,2.2-tr1fluoroethane Is used primarily as a
solvent and Is highly volatile, there Is a potential for exposure In the
workplace. Exposure will be both by Inhalation and dermal contact with the
vapor and liquid solvents. NIOSH (1988) estimated that 134,476 workers,
Including 50,482 wqmen, are exposed to 1,1,2-tr1chloro-l,2,2-tr1fluoroethane
In the workplace. 'In other NIOSH surveys, an air sample at one company
contained 0.70 ppra of I,l.2-tr1chloro-l,2,2-tr1fluoroethane (Chrostek. 1980)
and personal air samples for workers In another plant contained 1,1,2-trl-
chloro-1,2,2-tr1fluoroethane ranging from 0.2-6.7 ppm (Lee and Parkinson.
1982). A worker died and others were overcome while cleaning out a large
vapor degreaser; the concentration of 1.1,2-tr1chloro-l.2.2-tr1fluoroethane
may have been as high as 374,000 ppm (Anonymous, 1987). A comprehensive
survey of 1,1.2-tr1chloro-l,2,2-tr1fluoroethane levels In occupational atmo-
spheres In France reported that 1.5X of the workplaces had 1,1,2-trlchloro-
1.2,2-trlfluoroethane of which 10X were between 500 and the TLV value (1000
ppm) and 3X had levels >1000 ppm (Ensmlnger. 1988).
Results of surveys Indicate that the general population may be exposed
to I.1,2-tr1chloro-l,2,2-tr1fluoroethane In drinking water derived from
surface and underground sources. l,1,2-Tr1chloro-l.2,2-tr1fluoroethane has
been found In drinking water In the Great Lakes basin. In a survey In which
nine raw and treated Canadian water supplies were sampled once during each
of three seasons, and a tenth plant was sampled on 5 consecutive days 1n
0275d -16- 11/15/89
-------
each sampling period (Otson, 1987), 1-3 samples contained >0.1 wg/l of
1,1.2-tMchloro-l,2,2-trlfluoroethane In raw and treated water and an
additional 1-11 samples contained trace levels of the pollutant. It has
also been found In groundwater (1.3 wg/l) near a municipal solid waste
landfill (Sabel and Clark. 1984).
l.l,2-Tr1chloro-l,2,2-tr1fluoroethane would tend to partition In air,
rather than In soil and water, because of Us high volatility; therefore. If
1,1,2-trlchloro-l,2,2-trlfluoroethane 1s found In food, 1t would most likely
result from air Intake by a plant or animal. l,l,2-Tr1chloro-l,2,2-tr1-
fluoroethane was found In all eight samples of mothers' milk In a pilot
study; the levels were not quantified (PelUzzarl, 1982). The Infants of
these mothers would therefore be exposed to 1,1,2-trlchloro-l,2,2-trlfluoro-
ethane In their food.
0275d -17- 11/15/89
-------
4. ENVIRONMENTAL TOXICOLOGY
4.1. AQUATIC TOXICOLOGY
4.1.1. Acute Toxic Effects on Fauna. Pertinent data regarding the
effects of acute exposure of aquatic fauna to 1,l,2-tr1chloro-l,2,2-tr1-
fluoroethane were not located In the available literature In Appendix A.
4.1.2. Chronic Effects on Fauna.
4.1.2.1. TOXICITY — Pertinent data regarding the effects of chronic
exposure of aquatic fauna to I,1,2-tr1ch1oro-1.2,2-tr1fluoroethane were not
located In the available literature cited In Appendix A.
4.1.2.2. 8IOACCUHULATION/8IOCOHCENTRATION — Pertinent data regarding
the bloaccufflulatlon/bloconcentratlon potential of I,1,2-tr1chloro-l,2,2-tr1-
fluoroethane 1n aquatic fauna were not located In the available literature
cited In Appendix A. .
4.1.3. Effects on Flora.
4.1.3.1. TOXICITY — Pertinent data regarding the toxic effects of
exposure of aquatic flora to 1,1.2-tr1chloro-l,2.2-trlfluoroethane were not
located In the available literature cited In Appendix A.
4.1.3.2. BIOCONCENTRATION — Pertinent data regarding the bloconcen-
tratlon potential of I,l,2-tr1chloro-l,2.2-trlfluoroethane In aquatic flora
were not located In the available literature cited In Appendix A.
4.1.4. Effects on Bacteria. Pertinent data regarding the effects of
exposure of aquatic bacteria to 1,1,2-tr1chloro-1,2.2-tr1fluoroethane were
not located 1n the available literature cited In Appendix A.
4.2. TERRESTRIAL TOXICOLOGY
4.2.1. Effects on Fauna. Pertinent data regarding the effects of
exposure of terrestrial fauna to 1,l.2-tr1ch1oro-l,2,2-tr1f1uoroethane were
not located In the available literature cited In Appendix A.
0275d -18- 11 /15/89
-------
4.2.2. Effects on Flora. Pertinent data regarding the effects of
exposure of terrestrial flora to 1,1,2-tr1chloro-l,2,2-trlfluoroethane were
not located In the available literature cited In Appendix A.
4.3. FIELD STUDIES
Pertinent data regarding the effects of I.l.2-tr1chloro-l,2,2-tr1fluoro-
ethane on flora and fauna In the field were not located In the available
literature cited In Appendix A.
4.4. AQUATIC RISK ASSESSMENT
No data were available regarding the effects of exposure of aquatic
fauna and flora to I,l,2-tr1chloro-l,2,2-tr1fluoroethane, precluding the
development of freshwater and saltwater criteria by the method of U.S.
EPA/OWRS (1986).
4.5. SUMMARY
Pertinent data regarding the environmental toxlclty of 1.1,2-tMchloro-
1.2,2«-tr1fluoroethane were not located In the available literature cited In
Appendix A.
0275d -19- 11/15/89
-------
5. PHARHACOKINETICS
5.1. ABSORPTION
Experiments with humans (Morgan et al.. 1972). dogs (Trochlmowlcz et
al.. 1974) and rats (Andersen et al., 1980) Indicate that although vapors of
I,l,2-tr1chloro-l,2.2-tr1f1uoroethane are poorly absorbed by the pulmonary
system, measurable absorption occurs.
Morgan et al. (1972) administered vapors of "Cl-labeled 1,1,2-tM-
chloro-l,2,2-tr1fluoroethane to volunteers In single breaths and measured
the change In concentration of radioactivity In alveolar air with breath-
holding time and the elimination of radioactivity In breath during normal
•i
breathing over 30 minutes. The concentration of radlolabel Inlalveolar air
was -70-80% of the Initial concentration after 40 seconds of breath-holding.
In contrast, after only 10-20 seconds of breath-holding, concentrations of
"Cl-labeled 1,1,2-trlchloroethane In alveolar air had dropped to 10% of
the Initial concentration. In normal breathing experiments, 80.2% of the
radlolabel Inhaled 1n a single breath of I.l.2-tr1chloro-1,2,2-tr1fluoro-
ethane (and held for 5 seconds) was exhaled after 30 minutes, thus Indicat-
ing that 19.8% of Inhaled 1,1,2-tMchloro-l,2,2-trlfluoroethane was retained
In the body. About half of the radlolabel was exhaled during the first
minute, reflecting the low rate of absorption (Morgan et al.. 1972).
Andersen et al. (1980) could not measure loss of I.l,2-tr1chloro-l,2,2-
trlfluoroethane from the reclrculatlng atmosphere of a closed 31 l chamber
containing nine rats and air containing I.l,2-tr1chloro-l,2,2-tr1fluoro-
ethane at unspecified concentrations. This technique allowed measurement of
absorption rates of other vapors Including trlchloroethylene. The results
Indicate that net pulmonary absorption of 1,l,2-tr1chloro-l,2,2-tr1fluoro-
ethane was low. relative to other vapors.
0275d -20- 11/15/89
-------
Troch1mow1cz et al. (1974) measured arterial and venous concentrations
of I,l,2-tr1chloro-l,2,2-tr1fluoroethane In conscious beagle dogs during and
after 10-m1nute Inhalation exposures to three concentrations of I.l,2-tr1-
chloro-l,2.2-tr1fluoroethane vapors (1000. 5000 and 10,000 ppm). Blood
concentrations Increased rapidly during the first 5 minutes of exposure and
tended to level off (arterial) or Increase less rapidly (venous) thereafter
(Figure 5-1). Arterial blood levels of I.l,2-tr1chloro-l,2,2-tr1fluoro-
ethane Increased more rapidly than did venous blood levels, and both
arterial and venous blood levels Increased with Increasing exposure levels.
The data reinforce the existence of pulmonary absorption of 1,l,2-tr1chloro-
1,2.2-trlfluoroethane, Indicate that arterial blood levels reached apparent
steady-state within 10 minutes and demonstrate that blood levels were
proportional to exposure level-s.
The U.S. EPA (1983) reviewed unpublished data from Haskell Laboratory
(1968) regarding the dermal absorption of 1,1,2-tr1chloro-l,2,2-trlfluoro-
9
ethane In three human subjects. Liquid 1.1,2-tr1chloro-l,2,2-tr1fluoro-
ethane was applied to the scalp for 15 minutes or to the hands and forearms
for 30 minutes, and the concentration of 1,1,2-tr1chloro-l,2,2-trlfluoro-
ethane 1n the breath was measured at various times after termination of
exposure. The presence of 1,1,2-trlchloro-l,2,2-tr1fluoroethane In the
expired air Indicated that dermal absorption of I.l,2-tr1chloro-l,2,2-tr1-
fluoroethane occurred In the human body, but the data do not allow quantIta-
tlon of the extent of absorption.
Data regarding the rate and extent of gastric absorption of I.l.2-tr1-
chloro-1,2,2-tMfluoroethane were not located 1n the available literature
cited In Appendix A.
0275d -21- 11/15/89
-------
I"
It
* • io i*j a to u
MINUTE
FIGURE 5-1
Fluorocarbon 113 Concentration 1n Arterial and Venous Blood of
Beagle Dogs During and After I0-H1nute Exposures to Three
Inspired Levels (Four Dogs/Level)
Source: Trochlmowlcz et al., 1974
0275d
-22-
11/15/89
-------
5.2. DISTRIBUTION
In the dog experiments by Troch1mow1cz et al. (1974), concentrations of
1,l,2-tr1ch1oro-1,2.2-tr1fluoroethane In the blood dropped rapidly upon
termination of a I0-m1nute exposure (see Figure 5-1). Arterial blood
concentrations returned to control values by 15 minutes after termination of
exposure. Concentrations In venous blood decreased less rapidly than
arterial levels, but nevertheless were -80% decreased by 15 minutes after
termination of exposure. The data Indicate that, during pulmonary exposure,
blood contains I,l,2-tr1chloro-l,2,2-tr1fluoroethane, which can be distri-
buted to other parts of the body. The difference between the arterial and
venous concentrations both during and after exposure also suggests that
1,1,2-trlchloro-l,2,2-trlfluoroethane Is absorbed from the blood by tissues
and subsequently released after exposure.
Carter et al. (1970) determined levels of 1,l.2-tr1chloro-l,2,2-trl-
fluoroethane In the brain, liver, heart, fat. adrenal and thyroid of rats
exposed to 2000 ppm for 7-14 days. The data are presented In Table 5-1.
Concentrations of I,l,2-tr1chloro-l,2,2-tr1fluoroethane were much higher In
the fat than In the other tissues. Twenty-four and 48 hours following
termination of exposure, 1,1,2-trlchloro-l,2,2-tr1fluoroethane could only be
detected In fat, but levels In the fat also progressively decreased with
time after termination of exposure.
Savolalnen and PfaffH (1980) exposed rats to 1,l,2-tr1chloro-l,2,2-tr1-
fluoroethane at concentrations of 200, 1000 or 2000 ppm 6 hours/day, 5
days/week for 1 or 2 weeks and measured concentrations of 1,1,2-tMchloro-
1,2,2-tr1fluoroethane In the brain and per^renal fat. Concentrations In
both tissues Increased with Increasing exposure level, but duration of
0275d -23- 11/15/89
-------
TABLE 5-1
Tissue Concentrations of l,l,2-Tr1chloro-l,2,2-tr1fluoroethane
from Rats Exposed to A1r Containing 2000 ppm**1*
Exposure
Tissue
Brain (v»g/g)
Liver (yg/g)
Heart (ng/g)
Fat (yg/g)
Adrenal fug)
Thyroid (yg)
7 Days
22.73*1.00
15.77+0.87
16.59+2.56
722.48+71.29
8.39+2.61
1.09+0.46
14 Days
22.65+1.33
15.40+1.72
15.03+2.51
659.24+21.17
3. 47 +.0.34
0.94+2.00
Postexposure
24 Hours . 48 Hours
none none
none ' none
none none
108.45+33.62 5.60+2.94
none none
none none
aSource: Carterr et al., 1970
^Values are means + standard derivation of determinations from five rats.
027 5d
-24-
11/15/89
-------
exposure (1 week vs. 2 weeks) did not alter tissue concentrations signifi-
cantly. In agreement with the measurements of Carter et al. (1970), concen-
trations of I,l.2-tr1chloro-l,2,2-tr1fluoroethane In fat were much larger
(-20-fold) than concentrations In brain tissue (Savolalnen and Pfaffll,
1980).
5.3. METABOLISM
Data from experiments designed to Identify the metabolites of I,l,2-tr1-
chloro-l,2,2-trlfluoroethane In humans or animals are not available. The
only available Information Indicating a possible metabolic route Is the
observation that. In 1n vitro experiments. 1,1,2-trlchloro-l,2,2-trlfluoro-
ethane binds to cytochrome P-450 from rat hepatic mlcrosomes, thus suggest-
ing that 1,1,2-trlchloro-l,2,2-tMfluoroethane may be a substrate for oxlda-
tlve enzymes associated with P-450 (Va1n1o et al., 1980).
The observations that 1,l,2-tr1chloro-l,2,2-tr1fluoroethane Is preferen-
tially partitioned Into fatty tissues but rapidly disappears upon termina-
tion of exposure (Carter et al., 1970; Savolelnen and Pfaffll, 1980; Morgan
et al... 1972) has led to the suggestion that 1,1.2-trlchloro-l,2.2-trl-
fluoroethane 1s poorly metabolized In mammals (U.S. EPA, 1983). This
suggestion requires more direct evidence for substantiation, but corrobora-
tive evidence Is provided by Inhalation dog studies on the blotransformatlon
and elimination of 14C-1abe1ed homologous chlorofluorocarbons (trlchloro-
fluoromethane and dlchlorodlfluoromethane). In these studies, dogs were
given short-term (6-20 minutes) exposures to known amounts of the
14C-labeled compounds. Exhaled air and urine were collected for 1 hour
and 3 days after termination of exposure, respectively, and analyzed for
radioactivity. CO- was separated from other gases 1n the exhaled air aixd
analyzed for radioactivity. Essentially all (99-100%) of the administered
0275d -25- 11/15/89
-------
radioactivity was accounted for In the exhaled air. Radioactivity In
exhaled CO^ and In urine accounted for only traces (<1X) of the adminis-
tered dose (Blake and Hergner. 1974).
5.4. EXCRETION
1.l,2-Tr1chloro-1,2,2-tr1fluoroethane Is rapidly cleared from the
mammalian body, as Indicated by Its rapid disappearance from rat tissue
during postexposure periods (Carter et al., 1970) (see Table 5-1) and the
rapid decrease 1n blood concentrations of I,l,2-tr1ch1oro-1,2,2-tr1f1uoro-
ethane following* 1Q-m1nute Inhalation exposures In dogs (Troch1mow1cz et
al., 1974) (see Figure 5-1).
The appearance of 1,1.2-trlchloro-l ,2,2-tMfluoroethane In the exhaled
air of humans subjected to dermal exposures to 1,1,2-tr1chloro-1,2,2-tr1-
fluoroethane (Haskell Laboratory. 1968) Indicates that pulmonary exhalation
represents a significant route of excretion. Direct analysis of urine and
fecal matter for 1,1,2-tMchloro-l ,2.2-trlfluoroethane content following
exposure to 1,1,2-tr1chloro-l,2,2-tr1fluoroethane 1s not available, but In
dog studies on the elimination of homologous chlorofluorocarbons, only trace
amounts of radioactivity were found 1n the urine following acute Inhalation
exposures to 14C-1abe1ed compounds (Blake and Hergner, 1974).
5.5. SUWARY
Inhalation experiments In humans with "Cl-labeled 1,1.2-trlchloro-
1,2,2-trlfluoroethane (Morgan et al.. 1972) Indicate that, although pulmo-
nary absorption of 1,1.2-tr1chloro-1,2t2-tr1fluoroethane occurs, the rate of
absorption Is lower than that of other chlorinated hydrocarbons such as
trlchloroethane. Dermal absorption has also been shown to occur In humans
(Haskell Laboratory. 1968). but data regarding gastric absorption of
1,1.2-trlchloro-l.2.2-trlfluoroethane are not available.
0275d -26- 11/15/89
-------
Inhalation studies with dogs (Trochlmowlcz et al., 1974) and rats
(Carter et al., 1970; Salvolalnen and PfaffH, 1980) Indicate that absorbed
I,l,2-tr1chloro-l,2,2-tr1fluoroethane Is rapidly distributed by the blood to
various organs and tissues (Including the brain, liver, adrenal, heart and
thyroid) and 1s preferentially deposited Into fat.
Upon cessation of exposure, I,l,2-tr1chloro-l,2,2-tr1fluoroethane Is
rapidly cleared from the body. l,l,2-Tr1chloro-l,2,2-tr1fluoroethane could
not be detected In the brain, liver, heart, adrenal or thyroid of rats 24
and 48 hours after termination of a 14-day exposure regime, and I,l,2-tr1-
chloro-l,2,2-trlfluoroethane-levels In fat were decreased by -80 and 99%
during the same respective periods (Carter et al., 1970).
Human data Indicate that pulmonary exhalation Is a significant excretory
route for 1,1,2-tr1chloro-l,2.2-trlfluoroethane. l,l,2-Trlchloro-1.2.2-tr1-
fluoroethane was detected 1n the exhaled air of humans following dermal
administrations of 1,1,2-tMchloro-l,2,2-trlf luoroethane (Haskell Labora-
tory, 1968).
Identifications have not been made of in vivo metabolites of 1,1,2-trl-
chloro-1,2,2-trlfluoroethane In animals or humans. Based upon the demon-
stration of In vitro binding of 1,1,2-trlchloro-l,2,2-trlfluoroethane to rat
hepatic cytochromc P-450, a suggestion has been made that 1,1,2-tr1chloro-
1,2,2-tr1fluoroethane may be oxidized by enzymes associated with P-450
(Valnlo et al., 1980). but reaction products have not been Identified.
0275d -27- 11/15/89
-------
6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposure.
6.1.1.1. SUBCHRONIC — Data regarding the toxldty of subchronlc
exposure to 1,1,2-trlchloro-l,2.2-trlfluoroethane vapors are limited to a
single 84-day rat study. Groups of six male Sprague-Oauley rats were
exposed by whole-body Inhalation to 0 or 200 ppm I,l,2-tr1chloro-1,2,2-tr1-
fluoroethane (Industrial grade) for 8 hours/night for 84 days. Body weights
and urinary catecholamlne metabolites were monitored at Intervals throughout
the treatment period. After 84 days of treatment, the following endpolnts
were measured: liver and kidney weights, liver cytochrome P-450 content and
liver monooxygenase activity (with 7-ethoxycoumar1n as substrate). The
Imposed treatment did not significantly affect any of the measured endpolnts
(Blohm et al.. 1985).
6.1.1.2. CHRONIC ~ Trochlmowlcz et al. (1988) exposed groups of 100
male and 100 female Crl-.COBR rats to 0. 2000. 10.000 or 20.000 ppm 1.1,2-
trlchloro-1,2,2-trlfluoroethane 6 hours/day, 5 days/week for <24 months.
Hematologlcal analysis, chemical analysis of serum (for example, alkaline
phosphatase. blllrubln. urea nitrogen, cholesterol and total protein) and
urlnalysls (e.g.. pH. fluoride concentration, blood, protein and blllrubln)
were conducted on samples collected from 10 rats/sex/group at 3, 6, 12, 18
and 24 months. Body weights were measured periodically. All major organs
Including the heart, lungs, brain and nasal turblnates were examined macro-
scoplcally and microscopically upon death and. In the control and high-
exposure groups, at termination of the experiment. Tissues with gross
lesions or masses and nasal turblnates from rats In the low- and Interme-
diate-exposure groups were also examined microscopically at termination of
0275d -28- 11/15/89
-------
the experiment. Mo adverse effects were noted within any of the measured
endpolnts, with the exception that body weight was decreased relative to
that of controls 1n both sexes receiving the 20,000 ppm treatment and 1n
females treated with 10,000 ppm, especially after the first 50 weeks of
treatment. Survival In treated rats was comparable with that of control
rats. Some rats developed Cornybacterlure kutscherl Infections, which
resulted In deaths of 3-8% of the females and 20-39% of the males; the data
Indicated, however, that these Infections were not treatment-related
(Trochlmowlcz et a!.. 1988).
No adverse effects were noted In comparative examinations of 50 male
workers frequently exposed to 1,l,2-tr1chloro-l,2,2-tr1fluoroethane and 50
unexposed male workers. Average ages were 34 years (range > 23-51) and 37
years (range « 25-63) for exposed and unexposed workers, respectively.
Exposed workers worked an average 2.8 years (6 hours/day, 5 days/week) 1n
clean rooms In which 1,1,2-tr1chloro-l,2,2-trlfluoroethane was used dally
for general cleaning and degreaslng. Samples of air In these rooms Indi-
cated that 1,1.2-trlchloro-l.2,2-tr1fluoroethane concentrations ranged from
46-4700 ppm with a mean (n«161) of 699 ppm. Examination of the workers
Included the following: medical history, blood cell counts, visual profile.
electrocardiogram, audlometrlc test, serum analysis (e.g.. cholesterol.
blllrubln. BUN, glucose, alkaline phosphatase), chest X-ray and timed lung
vital capacity (Imbus and Adklns, 1972).
Epldenlologlcal and case-report studies suggest that subchronlc or
chronic occupational exposure to 1,l,2-tr1chloro-l,2,2-trlfluoroethane may
have neurotoxlc or neuropsychologlcal effects, but additional Information
and research 1s needed to substantiate these reports. In a questionnaire
0275d -29- 11/15/89
-------
study of Danish metal workers, workers exposed to I,l,2-tr1chloro-1,2,2-trl-
fluoroethane ("degreasers") more frequently provided positive answers to
questions regarding feelings of dizziness and drunkenness at work and
Irritability at home and work than did unexposed workers (Rasmussen and
Sabroe, 1986). Rasmussen et al. (1988) also reported that medical and
psychological examinations of 23 degreasers from a Danish metal factory that
exclusively used I.l,2-tr1chloro-l,2.2-tr1fluoroethane to clean metals
revealed 3 workers with characteristics of what the authors termed slight
psychoorganlc syndrome. These characteristics Included the following:
neuropsychologlcal symptoms such as Increased Irritability, headaches and
Impaired ability to concentrate and remember appointments and Instructions;
slight cerebral cortical atrophy In two of the three cases, as Indicated by
CT scanning; and below-normal performance In various psychological tests
(Rasmussen et al.. 1988). Raffl and Vlolante (1981) reported a case of
neuropathy In a woman who used liquid 1.1,2-tr1ch1oro-1.2.2-tr1f1uoroethane
dally to remove spots from clothes during the last 7 of 13 years In which
she worked as a laundress. During the previous 6 years she had used tetra-
chloroethylene. Exposure levels experienced by the woman were not esti-
mated. The woman complained of pain, paresthesla and weakness of the legs,
and electromyographlc examination revealed diminished motor nerve conduction
velocities In the left and right tlblalls nerves. The patient was advised
to curtail her exposure to 1.1.2-tr1chloro-1.2t2-tr1fluoroethane, and she
subsequently quit her job. The authors reported that the woman's condition
Improved after -4 months without exposure to 1,1,2-tr1chloro-l,2,2-tr1-
fluoroethane. but measured values for motor nerve conduction velocity In the
patient's tlblalls nerves were still below quoted normal values (Raffl and
Vlolante. 1981).
0275d -30- 11 /15/89
-------
6.1.2. Oral Exposure.
6.1.2.1. SUBCHRONIC — Pertinent data regarding the toxic effects of
subchronlc oral exposure to 1,1,2-trlchloro-l,2,2-trlfluoroethane were not
located In the available literature cited In Appendix A.
6.1.2.2. CHRONIC — Pertinent data regarding the toxic effects of
chronic exposures to orally administered I,l,2-tr1chloro-1,2,2-tr1f1uoro-
ethane were not located In the available literature cited In Appendix A.
6.1.3. Other Relevant Information. Steinberg et al. (1969) reported no
adverse effects In studies of dogs, guinea pigs and rats exposed to vapors
of 1,1,2-tr1ch1oro-1,2,2-tr1f1uorbethane at a concentration of 5100 ppm (6
-•?
hours/day. 5 days/week) for 4 weeks. Control and treated groups each
Included 2 dogs of both sexes, 10 female guinea pigs and 10 rats of both
sexes. No differences In the following endpolnts were observed between
control and treated groups In each species: growth rate; relative weights of
liver, spleen, lung and kidneys; and macroscopic and microscopic examina-
tions of liver, kidneys, lungs, trachea, heart and spleen. No treatment-
related alterations were observed In plasma lactic dehydrogenase. amylase
activity, BUN and values for hematocrU, percent neutrophlls and percent
lymphocytes In dogs. Rotobar performance and voluntary movement measured by
an activity wheel were unaffected by the treatment In rats (Steinberg et
al., 1969).
Carter et al. (1970) reported no significant changes In hematologlcal
values, clinical chemistries, electroencephalographlc findings, body weights
or relative organ weights In studies of 4 monkeys, 8 dogs, 40 mice and 50
rats exposed continuously to 2000 ppm 1,l,2-'tr1ch1oro-1,2,2-tr1fluoroethane
for 14 days. Controls consisted of 4 monkeys, 8 dogs, 20 mice and 25 rats.
0275d -31- 11/22/89
-------
Minor changes In liver cell histology, ultrastructure and biochemistry
were reported In male Wlstar rats (mean weight - 424 g) exposed to
I,l,2-tr1chloro-l,2,2-tr1f1uoroethane vapors at concentrations <2000 ppm as.
compared with sham-exposed controls. Groups of unspecified numbers were
exposed to 0, 200. 1000 or 2000 ppm 6 hours/day. 5 days/week for 1 or 2
weeks. Significant (p<0.01) changes In liver biochemical parameters
(decreased reduced glutathlone and activity of NAOPH cytochrome c reductase
and Increased activity of UDP-glucuronosyltransferase) were most prevalent
at the highest concentration provided. Light microscopy of liver sections
from all rats revealed Upld accumulation that appeared dose-related. The
only change revealed by electron microscopy was a "slight to moderate'
proliferation and vacuollzatlon of the smooth endoplasmlc retlculum In liver
cells from rats exposed to either 1000 or 2000 ppm. Exposure to 200 ppm
produced no effects associated with the liver (Valnlo et al.t 1980).
The acute lethality of l,l,2-tr1chloro-l,2.2-tr1fluoroeChane 1s low when
administered to animals by either oral or Inhalation routes. An oral LD5Q
of 43 g/kg was determined In Sprague-Oawley rats (Hlchaelson and Huntsman.
1964), but rabbits appeared to be more susceptible (Busey. 1967). Two of
eight rabbits died after three oral doses of 1 g/kg/day. When the dose was
Increased to 5 g/kg/day. half of the rabbits died after one or four doses
(Busey. 1967). In Inhalation experiments. Oesollle et al. (196B) determined
2-hour LCcQ values to be 95.000. 120.000 and 110.000 ppm for mice, guinea
pigs and rats, respectively.
Six-hour exposures of rats and dogs to lower concentrations of
I,l.2-tr1chloro-l,2,2-tr1fluoroethane vapors (11.000-13,000 ppm) were not
lethal, but caused CMS effects that disappeared after termination of
exposure (Steinberg et al.. 1969). Clark" and Tlnston (1982) determined an
0275d -32- 11/15/89
-------
ECgQ value for CMS effects In rats to be 28.000 ppm for 10-mlnute expo-
sures to 1,1,2-tr1chloro-l,2.2-tr1fluoroethane. Minor biochemical changes
(for example, Increased NAOPH-dlaphorase activity, decreased cerebral ..
glutathlone. Increased RNA) were noted In brain preparations from male rats
exposed to 1,1,2-tr1ch1oro-1,2,2-tr1fluoroethane concentrations <2000 ppm 6
hours/day, 5 days/week for 2 weeks {Savolalnen and PfaffH, 1980). The
observed changes were not dose-related, however, and the significance of the
changes In the CMS effects noted In other studies Is unclear.
Although the lethality of acute exposure to I,l,2-tr1chloro-l,2,2-tr1-
fluoroethane appears to be low, a number of human deaths have been attrib-
uted to acute exposure to high concentrations of 1.1,2-trlchloro-1,2,2-tr1-
fluoroethane and related halogenated hydrocarbons. During the late 1960s,
some people In the United States and other countries voluntarily Inhaled
aerosol products containing halogenated hydrocarbons Itke 1,1,2-tMchloro-
1,2,2-trlfluoroethane to obtain narcotic effects. The popularity of this
practice appears to have been short-lived, perhaps because of the sudden
deaths that sometimes occurred. By 1971, -65 deaths were attributed to this
practice (Relnhardt et al.. 1971a). The suddenness of death In otherwise
healthy Individuals, as well as the failure of autopsies to reveal the cause
of death, led to the hypothesis that halogenated hydrocarbons at high
concentrations cause cardiac arrhythmias, ventricular fibrillation and
cardiac arrest {Relnhardt et al., 1971a; Relnhardt and Haxfleld. 1973;
ZakhaM and Avlado. 1982). Accidental exposures to high concentrations of
halogenated hydrocarbons have also been reported. Hay and Blotzer (1984)
reported two cases of occupational deaths attributed to 1,1,2-trlchloro-
1,2,2-trlfluoroethane. In both cases, workers were exposed to high levels
of 1.1.2-tr1chloro-1.2.2-tr1fluoroethane vapors In confined spaces. The
0275d -33- 11/15/89
-------
first was exposed to -128.000 ppm for <45 minutes, but the exposure level
for the second worker was not available. The cause of death In both cases
was cardiac arrhythmia.
The hypothesis that high concentrations of I,l,2-tr1ch1oro-1,2,2-tr1-
fluoroethane vapors can cause adverse cardiovascular effects has received
support from a number of animal experiments (ZakhaM and Avlado. 1982).
When animals are exposed to a halogenated hydrocarbon and given an Injection
of eplnephrlne. arrhythmia can occur, as evidenced by electrocardlographlcal
signals. This effect, known as cardiac sensltlzatlon, has been observed In
unanesthetlzed dogs (Relnhardt and Maxfleld, 1973) and anesthetized mice
(Avlado and BeleJ, 1974). Hale beagle dogs were given eplnephrlne Injec-
tions (8 ug/kg) 5 minutes before and 5 minutes following Initial exposure
to I,l,2-tr1chloro-1,2.2-tr1f1uoroethane vapors. Exposure to I.l,2-tr1-
chloro-1.2.2-tr1f1uoroethane lasted 10 minutes. Cardiac arrhythmias were
observed In 3/4. 10/29 and 0/12 of the animals exposed to respective concen-
trations of 10.000. 5000. and 2500 ppm (Relnhardt and Maxfleld, 1973). Male
Swiss mice were exposed to a similar protocol, except that mice were
anesthetized with sodium pentobarbltal (0.7 mg/10 g bw), exposures were for
6 minutes and eplnephrlne doses (6 ug/kg) were administered 2 minutes
after the start of Inhalation. Cardiac sensltlzatlon to eplnephrlne was
observed In 3/3 and 1/3 of the mice exposed to 100.000 and 50,000 ppm,
respectively (Avlado and BeleJ. 1974). Unpublished data Indicated that.
without administration of exogenous eplnephrlne. cardiac arrhythmia did not
occur In dogs exposed to concentrations <20.000 ppm while running on a
treadmill (HullIn et al.. 1971) nor In dogs frightened by a loud noise or
electric shock and exposed to 10,000 ppm (U.S. EPA. 1983). Clark and
Tlnston (1973) compared the cardiac sensitizing potency of 14 halogenated
hydrocarbons administered by Inhalation with conscious beagle dogs.
0275d -34- 11/15/89
-------
Eplnephrlne (5 wg/kg) was administered Intravenously during the last 10
seconds of exposure and 10 minutes after exposure. The potency was directly
related to the saturated vapor pressures of the compounds. Inversely related
to their boiling points, but not related to structural features, molecular
weights or degree of fluorlnatlon. An EC5Q (concentration at which 50% of
the animals could be sensitized to exogenous eplnephrlne) of 10,000 ppm was
determined for 5-m1nute exposures to I,l,2-tr1chloro-l,2,2-tr1fluoroethane
(Clark and Tins ton, 1973). In rhesus monkeys anesthetized with sodium
pentobarbltal (30 mg/kg), 5-mlnute exposures to 25,000 and 50,000 ppm
I,l,2-tr1chloro-l,2,2-tr1fluorpethane caused arrhythmias and dose-related
•i
myocardlal depressions and tachycardia, without administrations of exogenous
eplnephrlne (BeleJ et al.. 1974).
Avlado and Smith (1975) reported that 5-m1nute .In. vivo exposures to
25,000 and 50,000 ppm 1,1,2-tr1chloro-l,2,2-tMfluoroethane decreased the
pulmonary resistance and Increased the pulmonary compliance In groups of
three anesthetized rhesus monkeys. Alarle et al. (1975) reported that In
vitro ventilation of excised rat lungs with vapors of 1,1,2-tr1ch1oro-1.2,2-
trlfluoroethane (concentration and period of exposure unspecified) produced
changes 1n pressure-volume relationships (compared with control excised
lungs) manifested predominantly by changes In surface tension at the
alveolar surface. Both of these studies Indicate that acute exposures to
high concentrations of I,1,2-tr1ch1oro-1,2,2-tr1fluoroethane may affect
pulmonary function; the authors of the latter report suggested that Inter-
actions of 1 ,l,2-tr1chloro-l,2,2-tr1fluoroethane with the normal surfactant
of the Inner alveolar surface are responsible for surface tension changes
that alter pulmonary function (Alarle et al., 1975).
0275d -35- 11/15/89
-------
Acute exposure to moderate concentrations of 1,1,2-trichloro-l,2,2-trl-
fluoroethane vapors can alter psychomotor function In humans. Stopps and
HcLaughUn (1967) administered psychophyslologlcal tests (manual dexterity
tests. Nee leer cube test, card sorting, addition of three single-digit
numbers and a clerical task test) to two men during -2-hour exposures to
I.l.2-tr1chloro-lt2.2-tr1f1uoroethane at concentrations of 0. 1500. 2500.
3500 or 4500 ppm. Performance was not affected at 1500 ppm, but Increas-
ingly declined at concentrations >2500 ppm. In a subsequent experiment to
examine the effects of dally 6-hour exposures to lower concentrations of
I.l.2-tr1chloro-l.2,2-tr1f1uoroethane. four men were exposed to 0 ppm, 6
hours/day. 5 days/week for 1 week, followed by a week of Identical exposures
to 500 ppm and then a week of Identical exposures to 1000 ppm (Relnhardt et
al.. 1971b). Performance In psychophysloloqlcal tests (Stopps and
Mclaughlin, 1967) was not affected by exposure to I,l.2-tr1chloro-l,2,2-tr1-
fluoroethane, and the subjects stated that they were unable to tell when
they were being exposed to the compound, except for a transient awareness of
odor upon first entering the exposure chamber. In addition, no adverse
effects were noted 1n a battery of examinations Including hematologlcal
analysis, serum chemistry (for example, alkaline phosphatase, BUN and
glucose), urlnalysls, chest X-ray and pulmonary function tests (for example.
diffusing capacity of lungs and fractional uptake of carbon monoxide)
(Relnhardt et al.. 1971b).
6.2. CARCINOGEMICITY
6.2.1. Inhalation. Data regarding the carc1nogen1c1ty of Inhalation
exposures to I,l,2-tr1chloro-l,2,2-tr1fluoroethane are limited to negative
results from the 24-month study of rats exposed to 1,1,2-tMchloro-l,2.2-
trlfluoroethane vapors at concentrations of 0. 2000. 10.000 or 20.000 ppm 6
0275d -36- 11/15/89
-------
hours/day, 5 days/week (Troch1mow1cz et al., 1988). Further experimental
details of this study are discussed In Section 6.1.1.2. Major organs and
tissues from the control and high-exposure groups were examined microscopic-
ally. Microscopic examination of organs and tissues of the low- and Inter-
mediate-exposure groups was limited to rats that died or were killed when
moribund during the study and to nasal passages and organs In which gross
lesions or tissue masses were Identified In rats killed at the end of the
experiment. Overall tumor Incidence and Incidences of Individual tumor
types were similar In all groups, with the exception that a significant
Increase In pancreatic Islet cell adenomas was observed \n female rats
exposed to 20,000 ppm (Table 6-1). The authors did not consider this Inci-
dence compound-related, because the Incidence of 5/86 was within historical
background levels for their laboratory, and female controls In a separate
but concurrent Inhalation study showed an Incidence of 6/95 for pancreatic
Islet cell adenomas. Tumors were also observed In the nasal passages of one
male rat from the 2000 ppm group and one female and three males from the
10.000 ppm group. The authors argued that this Incidence was not compound-
related because no two tumors were of the same cell type, there was no
dose-related trend and other preneoplastlc hlstologlcal changes were not
observed In the nasal passages at any exposure level.
6.2.2. Oral. Pertinent data regarding the cardnogenldty of oral
exposures to 1,!,2-tr1chloro-1,2,2-tr1fluoroethane were not located 1n the
available literature cited In Appendix A.
6.2.3. Other Relevant Information. Other pertinent data regarding the
cardnogenldty of 1,1,2-trlchloro-l ,2,2-tr1fluoroethane were not located In
the available literature dted In Appendix A.
0275d -37- 11/15/89
-------
TABLE 6-1
Incidence of Tumors In Crl-.CDBR Rats Exposed to Vapors of
l,l,2-Tr1chloro-l,2,2-tr1fluoroethane for 24 Months3
Sex
Exposure Levelb
(ppffl)
Tumor Type
Tumor Incidence
Female
Hale
0
2.000
10.000
20.000
0
2.000
10.000
20.000
pancreatic
Islet cell
adenomas
pancreatic
Islet cell
adenomas
0/85
0/36
0/30
5/86
2/88
1/64
0/58
2/87
QUALITY OF EVIDENCE
Strengths of Study: The compound was administered by a relevant route at
three levels to both sexes. Adequate numbers of
animals and adequate duration of exposure.
Weakness of Study:
Overall Adequacy:
Some decreased survival 1n all groups, which Is due to
respiratory Infection.
Study was of adequate design, but data were not
positive for carcinogenic effect. Authors reported
that Incidence for females at the high-exposure level
was within historical background Incidence level for
their laboratory.
aSource: Troch1mow1cz et al., 1988
''Rats were exposed 6 hours/day, 5 days/week for 24 months
0275d
ll/15/89
-------
6.3. HUTAGEMICITY
l,l,2-Tr1chloro-1,2.2-tr1fluoroethane was not mutagenlc In assays for
dominant lethal mutations 1n mice (Epstein et al., 1972) or In assays for
reverse mutations In numerous strains of Salmonella typhlmurlum (Simmon et
al.. 1977; Longstaff, 1988; Hahurln and Bernstein, 1988) (Table 6-2).
6.4. DEVELOPMENTAL TOXICITY
The U.S. EPA (1983) presented summaries of three unpublished studies.
one rat study (Ward, 1983) and two rabbit studies (Hazelton Laboratories.
1967a.b), regarding the possible teratogenlclty of 1 ,1.2-tr1chloro-1,2,2-
trlfluoroethane. Other teratogenlclty studies for 1,l,2-tr1chloro-l,2,2-
trlfluoroethane were not available. The summarized data Indicate that
1,1,2-tr1chloro-l,2,2-tr1fluoroethane was not teratogenlc 1n rats at the
experimental exposure levels, but conclusions are precluded 1n the rabbit
studies because of marked maternal toxldty and Inadequate numbers of
animals.
Ward (1983) exposed groups of 24 pregnant rats to 0, 5000. 12.500 and
25.000 ppm I,l,2-tr1chloro-l,2.2-tr1fluoroethane 6 hours/day on days 6-15 of
gestation. No macroscopic abnormalities were noted In dams of the treated
groups at autopsy. The only maternal effects noted were decreases In body
weight gain, food utilization and consumption and signs of hyperactlvlty In
the high-exposure group. The author reported that no evidence was found for
*
embryotox1c1ty. Increased Incidences of fetal ribs were reported at all
exposure levels, but the author stated that the Incidences were within the
control range.
Hazelton Laboratories (1967a) exposed groups of 12 rabbits to 0. 2000 or
20,000 ppm I,l,2-tr1chloro-l,2,2-tr1fluoroethane 2 hours/day on days 8-16 of
presumed gestation. The respective groups, however, only contained 4. 4 and
0275d -39- 11/15/89
-------
Wl
O
TABLf 6-2
Nutagenlclty Testing of l,l,2-TMchloro-1.2.2-tr1Muoroethane
Assay
Ooatnant
lethal
•utatlon
Reverse
•utatlon
Reverse
•utatlon
Reverse
•utatlon
Compound
Indicator/ and/or
Organise Purity
ICR/Ha Swiss NR
•Ice
SalaonelU coanerctal
typhlaurluB
TA1535. TA1S37,
TA1538. TA98
TA100
S. tvphlMrliM coMwrclal
Al 5. TAOO |>N.»>
yyphlMirluM coMwrclal
and TA100
Application
single tntra-
perltoneal
application
vapors In closed
desiccator, 7-10
hours
vapors In closed
systea, 72 hours
NR
Concentration Activating Response Content
or Dose 4 System
200, 1000 ng/kg NA - 7 and 9 wles treated
at low and high dose.
respectively, 8 weeks
of Mtlng. Incidence of
early fetal deaths and
prelnplanatlon losses
within control Units
NR NR - Tested at < toxic con-
centration
NR NR - IA1535 tested at concen-
trations OOO.OOO ppm;
TA100 tested at concen-
trations <200,000 ppM
NR *S-9 - further details not pre-
sented
Reference
Epstein et al.,
1972
Simon et al..
1977
Longs taff. 1968
Kahurln and
Bernstein. 1968
NA - Not applicable; NR - not reported
oo
10
-------
7 rabbits that were actually pregnant. Maternal toxldty. evident In the
high-exposure group, was characterized by lowered body weight gain during
exposure, eye Irritation, premature delivery In one doe and death of
another. Examinations were made of the external soft-tissue and skeletons
of 19, 8 and 24 fetuses for the control, low- and high-exposure groups,
respectively. No differences were noted among the groups of offspring,
except that one pup In the low-exposure group and two In the high-exposure
group were dead at examination. In an oral study, groups of eight female
rabbits were administered 0, 1 or 5 g/kg I.l,2-tr1chloro-l.2,2-tr1fluoro-
ethane by gavage on days 8-11 of presumed gestation (Hazelton Laboratories,
•i
1967b). Pregnancy was obtained, however. In only three, six and four
rabbits In the control, low- and high-exposure groups, respectively. Two
and three of the pregnant females died In the low- and high-exposure groups,
respectively. Maternal toxldty was also Indicated by body weight loss and
reduced food and water consumption 1n«the high-exposure group. The marked
maternal toxldty precluded evaluation of fetotoxldty and teratogenldty
data.
6.5. OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding other reproductive effects of 1,1,2-tr1chloro-
l.2.2-tr1fluoroethane were not located In the available literature cited In
Appendix A.
6.6. SUMMARY
Adverse systemic effects In animals caused by long-term exposure (sub-
chronic or chronic) to vapors of 1,l,2-tr1chloro-l,2,2-trlfluoroethane at
concentrations <2000 pom have not been Identified, but the data base Is
limited to two rat studies (Blohm et al., 1985; Trochlmowlcz et al., 1988).
0275d -41- 11/15/89
-------
At concentrations >10.000 ppm. adverse body weight changes were observed In
rats (Trochlmowlcz et a!.. 1988). No adverse changes In body. IWer or
kidney weights, liver biochemistry or urinary catecholamlne metabolites were
observed 1n rats exposed to 1.1,2-trlchloro-l,2.2-trlfluoroethane vapors at
concentrations of 200 ppm for 84 days (Blohm et al.. 1985). Chronic
'exposure (24 months) of rats to 1,1,2-trlchloro-l,2,2-tr1fluoroethane vapors
at 2000 ppm caused no adverse changes 1n blood and urine chemical Indices.
body and organ weights or In the histology of major organs and tissues
(Trochlmowlcz et al.. 1988). The same endpolnts were unaffected by higher
chronic exposure levels, except for body weight gain, which was decreased In
both sexes of rats exposed to 20.000 ppm and In fe'male rats exposed to
10.000 ppm.
No adverse effects were Identified In shorter-term studies of dogs,
guinea pigs and rats exposed to vapors of 1,1,2-tr1chloro-l,2,2-tr1f1uoro-
ethane at concentrations of 5100 ppm for -4 weeks (Steinberg et al., 1969).
Carter et al. (1970) also reported no adverse effects In Inhalation studies
of monkeys, dogs, mice and rats continuously exposed to 2000 ppm for 14 days.
The only report of 1,1,2-tr1chloro-l.2.2-tr1fluoroetnane-tnduced
systemic effects other than body weight changes In animals exposed to low to
moderate concentrations comes from a 2-week Inhalation study of rats (Valnlo
et al.. 1980). Light microscopy revealed Upld accumulation and electron
microscopy revealed changes 1n the smooth endoplasmlc retlculum In liver
cells from rats exposed to concentrations of 1000 or 2000 ppm. Changes were
also noted In enzymlc activities and reduced glutathlone levels In the liver
of rats exposed to 2000 ppm (Valnlo et al.. 1980).
Adverse systemic effects of long-term exposure of humans to vapors of
I,l.2-tr1ch1oro-l,2.2-tr1f1uoroethane have not been clearly Identified.
0275d -42- 11/15/89
-------
In a comparison of chronically exposed human workers with unexposed workers
(Irnbus and Adklns, 1972). no adverse effects were noted 1n physical examina-
tions of workers who worked an average 2.8 years In rooms 1n which average.
concentrations of I.l.2-tr1chloro-l,2,2-tr1fluoroethane were estimated to be
699 ppm. Epldemlologlcal and case-report studies suggest, however, that
long-term occupational exposure to vapors of 1.1.2-tr1ch1oro-l,2,2-tr1-
fluoroethane may cause neuropsychologlcal effects (Rasmussen and Sabroe,
1986; Rasmus sen et al., 1988) or neuropathy (Raffl and Vlolante. 1981).
Further Information Is needed to substantiate the suggestions of the
ep1dem1o1og1ca1 and case-report studies.
Acute exposures (<2 hours) to moderate concentrations (>2500 ppm) of
I.1,2-tr1chloro-l>2.2-tr1f1uoroethane vapors altered the performance of
volunteers In psychophyslologlcal tests (Stopps and Mclaughlin. 1967).
Exposure of volunteers to lower concentrations (<10QO ppm) for a longer
duration (6 hours/day. 5 days/week for 2 weeks) did not cause treatment-
related changes In performance In psychophyslologlcal tests or In physical
examinations (Relnhardt. et al.. 1971b).
The acute lethality of 1,1,2-tr1chloro-l,2,2-tr1fluoroethane Is low when
administered to animals by either oral or Inhalation routes. An oral LDg_
of 43 g/kg was determined for rats (Hlchaelson and Huntsman, 1964), but
rabbits appeared more susceptible. Half of a group of eight rabbits died
after receiving one to four doses of 5 g/kg/day (Busey, 1967). Two-hour
LC5Q values of 95.000. 120,000 and 110,000 ppm were determined for
Inhalation exposures of mice, guinea pigs and rats, respectively (Oesollle
et al.. 1968).
Acute exposures to moderate to high concentrations of 1,1,2-trlchloro-
!,2.2-tr1f1uoroethane caused CNS effects In two animal species. Reversible
0275d -43- 11/15/89
-------
CMS effects were seen In dogs and rats given 6-hour exposures to
11.000-13.000 ppm (Steinberg et al.. 1969), and an EC5Q value of 28.000
ppra was determined for CMS effects In rats given 10-mlnute exposures (Clark
and Tins ton, 1982). The mechanistic connection between these CMS effects
and the observation of minor biochemical effects In brain preparations from
rats exposed to concentrations <2000 ppm for 2 weeks (Savolalnen and
Pfaffll, 1980) currently Is unclear.
Accidental and voluntary human exposures to high concentrations of
I,1,2-tr1ch1oro-l,2,2-tr1fluoroethane vapors caused sudden death generally
thought to be due to cardiac arrest (Hay and Blotzer. 1984; Relnhardt et
al.. 1971a. 1973; ZakhaM and Avlado. 1982). This hypothesis has received
support from animal studies In which acute exposures (5-10 minutes) to
moderate to high concentrations caused adverse cardiac effects. Cardiac
sensltlzatlon to eplnephrlne-Induced arrhythmias was observed In dogs at
concentrations >5000 ppm (Relnhardt et al.. 1973) and In anesthetized mice
at concentrations >50,OQO ppm (Avlado and BeleJ, 1974). An EC5Q for
cardiac sensltlzatlon of 10,000 ppm was determined for S-mlnute exposures of
dogs (Clark and Tlnston, 1973). In anesthetized rhesus monkeys, 5-minute
exposures to concentrations >25,000 ppm caused arrhythmias, myocardlal
depressions and tachycardia, without administration of exogenous eplnephrlne
(BeleJ et al.. 1974).
Acute 5-m1nute exposures to vapors of I,l,2-tr1chloro-l,2,2-tr1f1uoro-
ethane at concentrations >25,000 ppm altered pulmonary function In rhesus
monkeys (Avlado and Smith, 1975). In. vitro experiments with excised rat
lungs (AlaMe et al.. 1975) Indicated that this effect may Involve Inter-
action of 1,l.2-tr1chloro-1,2.2-tr1f1uoroethane with surfactant on the Inner
alveolar surface.
027 5d -44- 11/15/89
-------
Pertinent data regarding the systemic toxlclty of chronic or subchronlc
exposure to orally administered 1.1,2-trlchloro-l,2,2-trlfluoroethane were
not located In the available literature cited In Appendix A.
Data regarding the carclnogenlcHy of I,l,2-tr1chloro-l,2,2-tr1fluoro-
ethane are limited to a 2-year Inhalation study 1n which rats were exposed
to concentrations of 0. 2000, 10,000 or 20,000 ppm (Trochlmowlcz et a!..
1988). No treatment-related Increases In tumor Incidences were reported.
1,1,2-tr1chloro-l,2,2-trlfluoroethane was not mutagenlc In assays for
dominant lethal mutations In mice (Epstein et al., 1972) nor In assays for
reverse mutations In S_. typhlmurlum (Simmon et al., 1977; Longstaff, 1988;
Mahurln and Bernstein, 1988).
The U.S. EPA (1983) summarized three unpublished studies (Ward, 1983;
Hazelton Laboratories, 1967a,b), which contain the only available data
regarding the teratogenlclty and other reproductive effects of 1,1,2-trl-
chloro-1,2,2-trlfluoroethane. The summarized data Indicate that I,l,2-tr1-
chloro-1,2,2-tr1fluoroethane was not teratogenlc In rats exposed to air
containing <25,000 ppm on days 6-15 of gestation (Ward, 1983), but conclu-
sions were precluded In rabbit studies (Hazelton Laboratories, 1967a,b)
because of marked maternal toxlclty and Inadequate numbers of animals.
0275d -45- 11/15/89
-------
7. EXISTING GUIDELINES AND STANDARDS
7.1. HUHAN
The ACGIH (1986) established a TLV-TWA of 1000 ppra (7600 mg/m») and a
TLV-STEL of 1250 ppro (9500 mg/ma) for 1.1,2-tr1ch1oro-1.2,2-tr1fluoro-
ethane. These limits were thought to provide margins of safety against
systemic effects and cardiac sensltlzatlon such as that observed In dogs
given 5-ra1nute exposures to 5000 ppm I,l,2-tr1chloro-l,2,2-tr1fluoroethane
(38344 mg/m*} In conjunction with Intravenous eplnephrlne (Relnhardt et
al., 1973) (see Section 6.1.3.).
OSHA (1989) established limits of 1000 ppm (7600 mg/m') as an 8-hour
TWA and 1250 ppm (9500 mg/m») as a 15-minute STEL for 1.1.2-trlchloro-
1,2,2-trlfluoroethane. These limits were established to provide margins of
safety against cardiac sensltlzatlon as discussed above and to reduce the
risk of Impaired psychomotor performance such as that reported by Stopps and
HcLaughlln (1967) to occur In humans during 2-hour exposures to concentra-
tions >2500 ppm (19.172 mg/m*) (see Section 6.1.3.).
The U.S. EPA (1989) lists a verified RfO of 30 mg/kg/day for oral expo-
sure to I.l,2-tr1chloro-l.2.2-tr1fluoroethane. This RfO 1s being reconsid-
ered and Is pending change. The basis for the RfO Is the observation of no
adverse effects 1n humans occupatlonally exposed to vapors of 1.1,2-tM-
chloro-1,2,2-trlfluoroethane at an average concentration of 699 ppm (5358
mg/ra«) for an average 2.77 years (Imbus and Adklns. 1972). To derive the
RfO, the average exposure concentration was converted to an oral dose
equivalent of 273 mg/kg/day. divided by an uncertainty factor of 10 and
rounded to 30 mg/kg/day.
0275d -46- 11/15/89
-------
7.2. AQUATIC
Pertinent guidelines and standards for the protection of aquatic life
from exposure to 1,2.2-trlchloro-l.1,2-tr1fluoroethane were not located In
the available literature cited In Appendix A.
0275d -47- 11/15/89
-------
B. RISK ASSESSMENT
8.1. CARCINOGENICITY
8.1.1. Inhalation. Data regarding the cardnogenldty of Inhaled
1.1.2-tr1ch1oro-1.2,2-tr1fluoroethane In humans were not located. No
treatment-related tumorlgenlc effects were noted In a 24-month Inhalation
study of rats (Trochlmowlcz et al., 1988). Groups of 100 Crl:COBR rats of
both sexes were exposed to 0, 2000, 10,000 or 20,000 ppm 1,1,2-trlchloro-
1.2.2-trlfluoroethane (15.328, 76,638, 153,276 mg/m«) 6 hours/day, 5
days/week.
8.1.2. Oral. Pertinent data regarding the carclnogenlclty of oral
exposure of humans or animals to 1 ,!,2-tr1chloro-l,2,2-tr1f1uoroethane were
not located In the available literature cited In Appendix A.
8.1.3. Other Routes. Data regarding the cardnogenldty of 1,1,2-tM-
ch1oro-1,2,2-tr1fluoroethane by other routes of exposure or other data
regarding the carclnogenlclty of 1,1,2-trlchloro-l,2,2-tr1f1uorc«thane were
not located In the available literature cited In Appendix A.
8.1.4. Height of Evidence. No data were available regarding the carclno-
genlclty of 1.1,2-tr1chloro-l ,2,2-trlfluoroethane to humans. A single
Inhalation experiment using rats (Trochlmowlcz et al., 1988) provided the
only available test for the cardnogenldty of 1,l,2-tr1ch1oro-l,2,2-tr1-
fluoroethane 1n animals. According to the EPA classification scheme for
carcinogenic risk assessment adopted by the U.S. EPA (1986b), 1,l.2-tr1-
chloro-l,2,2-tr1fluoroethane Is assigned to EPA Group 0, not classifiable as
to human cardnogenldty. Assignment to Group E, evidence for noncardno-
genldty for humans, requires. In the absence of human data, at least two
animal tests of two species (U.S. EPA, 1986b). and Is therefore Inappro-
priate for I,1,2-tr1chloro-1.2,2-tr1fluoroethane.
0275d -48- 12/05/89
-------
8.1.5. Quantitative Risk Estimates.
8.1.5.1. INHALATION ~ The only carclnoqenlcHy data located were the
negative studies using rats (Trochlmowlcz et al.. 1988). Therefore, quanti-
tative estimation of carcinogenic risk associated with Inhalation exposure
to I,l,2-tr1chloro-l,2.2-tr1fluoroethane cannot be made.
8.1.5.2. ORAL — Lack of data precludes quantitative estimation of
carcinogenic risk associated with oral exposure to I,l,2-tr1chloro-l,2.2-
trlfluoroethane.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure.
8.2.1.1. LESS THAN LIFETIME (SUBCHRONIC) — The data base for
subchronlc Inhalation exposure to I,l,2-tr1chloro-l,2,2-tr1fluoroethane
contains only an 84-day rat study (Blohm et al., 1985). No adverse effects
were observed In body weights, liver and kidney weights, urinary levels of
catecholamlne metabolites or Indices of liver biochemistry In rats exposed
to 200 ppm 1,1,2-trlchloro-l,2.2-tr1fluoroethane (1533 mg/m*) for 8
hours/night for 84 days (Rec. 13). Because of the relative Inadequacies of
this study (no LOAEL was Identified, a single exposure level and small
numbers of animals were used, and no hlstopathologlcal examinations were
performed), the chronic RfD of 27 mg/m» (Section 8.2.1.2.) Is adopted as
the RfD for subchronlc Inhalation exposure to I,l.2-tr1chloro-l,2,2-tr1-
fluoroethane.
8.2.1.2. CHRONIC —The data base for chronic Inhalation exposure to
1,1,2-tr1chloro-l,2,2-tr1fluoroethane Includes two studies suitable for use
In risk assessment: a 24-fflonth Inhalation study of rats (Trochlmowlcz et
al., 1988) and an ep1den1olog1cal study of human workers frequently exposed
to I,l,2-tr1chloro-l,2.2-tr1fluoroethane (Imbus and Adklns, 1972).
0275d -49- 11/15/89
-------
No adverse effects were noted In comparative physical examinations of 50
male workers exposed to 1,1.2-tr1chloro-1.2.2-tr1fluoroethane and 50
unexposed workers (Imbus and Adklns. 1972). Exposed workers worked an
average 2.8 years (6 hours/day. 5 days/week) In rooms containing air with an
average I,l.2-tr1chloro-l,2,2-tr1fluoroethane concentration of 699 ppm (5357
mg/ra3), as Indicated by 161 air samplings. Thus, 5357 mg/m3 represents
a NOEL In this study, but a LOAEL was not Identified (Rec. |4).
The rat study (TrocMmowIcz et al.. 1988} provides a more suitable basis
for derivation of an RfD for chronic Inhalation exposure to 1,1,2-trlchloro-
1,2,2-tr1fluoroethane because: more precisely defined, multiple exposure
levels were employed; the duration of exposure was an entire lifetime;
•
hlstopathologlcal examinations were conducted; and both a NOEL and a LOAEL
were Identified (Recs. fl, 2). Rats were exposed to 0, 2000. 10.000 or
20.000' ppm 1.1.2-tr1chloro-i,2,2-tMfluoroethane (15.328. 76,638 and 153.276
mg/m») 6 hours/day. 5 days/week for <24 months. No adverse effects were
noted at any exposure level In hematologlcal and blood chemical Indices,
urlnalysls and hlstopathologlcal examinations of all major organs.
Decreased body weight gain was noted In both sexes receiving the 153.276
mg/ra» treatment and 1n females exposed to 76,638 mg/mj (Rec. |2). The
76,638 mg/m* level thus represents a LOAEL for decreased body weight In
female rats and the 15.328 mg/m* level represents a NOEL (Rec. fl).
In studies of dogs given 10-mlnute exposures to 1.1,2-tMchloro-l,2,2-
trlfluoroethane (Troch1mow1cz et al., 1974), apparent steady-state levels of
I,l,2-tr1chloro-l,2,2-tr1fluoroethane were reached In arterial blood within
10 minutes of the start of exposure (see Section 5.1. and Figure 5-1).
Therefore, assuming that a steady state Is attained In the blood during
6-hour/day exposures and that the blood/gas partition coefficient for
0275d -50- 11/15/89
-------
I,1,2-tr1chloro-1,2,2-tMfluoroethane Is the same In rats and humans, the
rat NOEL of 15,328 mg/ma following exposure for 6 hours/day, 5 days/week
1s the HEC associated with no effects. Adjusting for Intermittent exposure
and applying an uncertainty factor of 100 (10 to extrapolate between species
and 10 to protect the most sensitive Individuals) yields an RfD of 27
mg/m» for chronic Inhalation exposure to I,l,2-tr1chloro-l.2.2-tr1fluoro-
ethane. This concentration Is well below the lowest levels associated with
cardiac sensltlzatlon to exogenous eplnephrlne In dogs (5000 ppm or 38.319
mg/m3 for 10 minutes) (Relnhardt et a!., 1973) and those associated with
human psychomotor Impairment (2500 ppm or 19,160 mg/m» for 2 hours)
(Stopps and Mclaughlin. 1967) In acute studies (Recs. 120. 25).
Confidence In the key study Is high. More than adequate numbers of
animals were exposed to multiple concentrations, multiple endpolnts were
measured and both a LOAEL and NOEL were Identified. Confidence In the data
base Is medium. Human acute experimental exposure studies (Stopps and
Mclaughlin, 1967; Relnhardt et a!.. 1971a.b) and an occupational exposure
study (Imbus and Adklns, 1972) found no adverse effects at concentrations
lower than the chronic rat NOEL. Although microscopy revealed minor hlsto-
loglcal and ultrastructural changes In liver cells of rats exposed to
concentrations of 1000 and 2000 ppm (7664 and 15,328 mg/ma) for 2 weeks
(Valnlo et al.. 1980) (Rec. #12). the key study Identified (with light
microscopy) no hlstopathologlcal liver effects upon much longer duration of
exposure and at concentrations <20,000 ppm (153,276 mg/m'). Summarized
data from a rat study Indicate that 1,l,2-tr1chloro-l,2.2-tr1fluoroethane
was not teratogenlc (Ward, 1983). but the data were not available for
review, and adequate supporting studies of the reproductive and teratogenlc
effects of 1,1,2-tr1chloro-l,2.2-tr1f1uoroethane are not available.
Reflecting confidence In the data base, confidence 1n the RfO Is medium.
0275d -51- 11/15/89
-------
8.2.2. Oral Exposure.
8.2.2.1. LESS THAN LIFETIME (SUBCHRONIC) -. Data were not located
regarding toxlclty following subchronlc oral exposure to 1.1.2-trlchloro-
1,2,2-trlfluoroethane In humans or animals. Lacking sufficient data, the
RfO of 3 mg/kg/day for chronic oral exposure to I.l.2-tr1chloro-l,2,2-tr1-
fluoroethane Is adopted for subchronlc oral exposure. Confidence In this
RfD Is low. as explained In the next section.
8.2.2.2. CHRONIC — Data were not located regarding the chronic
toxlclty of 1,l,2-tr1chloro-l,2.2-tr1fluoroethane In humans following oral
exposure. The chronic Inhalation study of rats (Trochlmowlcz et al., 1988),
In which a LOAEL of 10.000 ppm (76,638 mg/m») and a NOEL of 2000 ppm
(15.328 mg/m") 6 hours/day. 5 days/week were Identified, may serve as the
basis for an RfO for chronic oral exposure to 1,l,2-tr1chloro-l,2,2-tr1-
fluoroethane.
An equivalent dose of 1713 mg/kg/day Is estimated by expanding the rat
NOEL concentration of 2000 ppm (15.328 mg/m») to continuous exposure,
multiplying the result by the Inhalation rate for rats of 0.231 m'/day
estimated according to U.S. EPA (1980). and dividing by the time-weighted
average body weight of 0.369 kg for females exposed to 2000 ppm. estimated
from graphic data In the published report (Trochlmowlcz et al.. 1988). An
equivalent absorbed dose of 343 mg/kg/day Is estimated by multiplying the
equivalent dose by an absorption factor of 0.2. The absorption factor Is
based upon breath-holding experiments with humans (Morgan et al., 1972) (see
Section 5.1.). which Indicated that -20% of the I.l.2-tr1chloro-l,2,2-tr1-
fluoroethane Inhaled In a single breath and held for 30 seconds was absorbed
by the pulmonary system, and the assumption of 100X gastric absorption of
0275d -52- 11/15/89
-------
I,l,2-tr1chloro-l,2,2-tr1fluoroethane. The absorption factor for Inhalation
exposure Is likely to be an overestimate, because 1t was obtained under
nonsteady-state conditions.
The estimated equivalent absorbed dose 1s divided by an uncertainty
factor of 100 (10 to extrapolate between species and 10 to protect the most
sensitive Individuals) to derive an RfD of 3 mg/kg/day or 210 mg/day for a
70 kg human for chronic oral exposure to I.l,2-tr1chloro-l,2,2-tr1fluoro-
ethane. Confidence In this RfD Is low because of the uncertainty associated
with route-to-route extrapolation.
0275d -53- 11/15/89
-------
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The toxlclty of I,l,2-tr1ch1oro-l.2,2-tr1fluoroethane was discussed In.
Chapter 6. The only observation of an adverse effect caused by subchronlc
or chronic exposure to nonlethal concentrations of I,l,2-tr1chloro-l,2,2-
trlfluoroethane comes from the 24-month Inhalation study of rats
(Trochlmowlcz et al., 1988) In which decreased body weights relative to
controls were observed In rats exposed to either 20,000 ppm (both sexes) or
10.000 ppm (females only) for 6 hours/day. 5 days/week. The dose-effect
data for the lower of the two exposure levels associated with this response
are summarized In Table 9-1. A CS Is calculated for each study and
presented In Table 9-2. Although a CS of 4 has been calculated for both
studies In Table 9-2, the study In which female rats were exposed to 10.000
ppm was chosen to represent the chronic toxlclty of 1,l,2-tr1chloro-1.2,2-
trtfluoroethane because of Its lower NED value (Table 9-3).
9.2. BASED ON CARCINOGENICITY
As reviewed In Chapter 6. carclnogenldty data for 1.1,2-trlchloro-
1.2,2-trlfluoroethane are limited to the negative Inhalation studies of rats
(Trochlmowlcz et al.. 1988). In Chapter 8. 1,1,2-tr1chloro-l,2,2-tr1fluoro-
ethane was assigned to EPA Group 0, not calsslfIcable as to human carclno-
genldty. Because of lack of positive data, quantitative estimates of
cancer risks cannot be derived; therefore, hazard ranking based on carclno-
genldty Is not possible for I,l,2-tr1chloro-1.2.2-tr1fluoroethane.
0275d -54- 11/15/89
-------
o
ro
LM
a.
ui
TABLE 9-1
Inhalation Toxtclty Summary for l.l.2-Tr1chloro-1.2,2-Tr1fluoroethanea-b
Sex
No. at
Start
Average
Body
Weight
(kg)
Transformed
Exposure Animal Oosec
(mg/kg/day)
Equivalent
Human Dose1'
(mg/kg/day)
Response
100
0.369e
100
0.369e
20,000 ppm
(153.276 mg/n»»)
6 hours/day,
5 days/week.
for 24 months
10,000 ppm
(76,638 mg/m>)
6 hours/day.
5 days/week,
for 24 months
17,134
2982
8,567
1491
Decreased body
weight relative
to controls
Decreased body
weight relative
to controls
'Source: Trochlmowtcz et al., 1988
bThe vehicle/physical state was vapor and the purtty of the compound was 99.89X.
Calculated by multiplying the exposure concentration In mg/m* by 6 hours/24 hours x 5 days/7 days x
rat Inhalation rate [0.231 «»/day for a rat weighing 0.369 kg (U.S. EPA, 1980)]
''Animal dose Is scaled to the human dose by a surface area scaling factor (body weight 2/3).
eAverage of body weights at 10, 30. 50, 70 and 90 weeks for females exposed to 20,000 ppm
to
^
CD
-------
TABLE 9-2
Inhalation Composite Score for 1,1,2-TMchloro-l,2,2-Tr1f1uoroethane
Using the Rat*
Dose/
Duration
{ rag/kg/day)
17,134
8, 567
Chronic
Human NEOb
(mg/day)
208,740
104.370
RVd Effect RVe CS
1 Decreased body 4 4
weight relative
to controls
1 Decreased body 4 4
weight relative
to controls
RQ
5000
5000
aSource: Trochlmowlcz et al., 1988
^Calculated by multiplying the equivalent human dose (expressed as mg/kg/
day) by 70 kg. the reference human body weight
0275d
-56-
11/15/89
-------
TABLE 9-3
l,1.2-Tr1chloro-1,2.2-tr1fluoroethane
Minimum Effective Dose (NED) and Reportable Quantity (RQ)
Route: Inhalation
Species/Sex: rat/female
Dose*: 104,370 mg/day
Duration: 24 months
Effect: decreased body weight relative to controls
RVd: 1
RVe 4
CS: 4
RQ: 5000
Reference: Troch1mow1cz et al.. 1988
•Equivalent human dose
02754
.57. 11/15/89
-------
10. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986..
Documentation of the Threshold Limit Values and Biological Exposure Indices.
5th ed. Cincinnati, OH. p. 603-604.
AlaMe, Y., C. Barrow, H.A. Choby and J.F. Quealy. 1975. Pulmonary atelec-
tasls following administration of halogenated hydrocarbons. Toxlcol. Appl.
Pharmacol. 31: 233-242.
Amoore, J.E. and E. Hautala. 1963. Odor as an aid to cheml'cal safety: Odor
thresholds compared with threshold limit values and volatilities for 214
Industrial chemicals In air and water dilution. J. Appl. Toxlcol. 3(6):
272-290.
Andersen, M.E., M.I. Gargas, R.A. Jones and L.J. Jenkins, Jr. 1980. Deter-
mination of the kinetic constants for metabolism of Inhaled toxicants In
vivo using gas uptake measurements. Toxlcol. Appl. Pharmacol. 54(1):
100-116.
Anonymous. 1987. Fatal Accident Circumstances and Epidemiology (FACE)
Report: Worker dies while cleaning Freon 113 degreasing tank In Virginia.
November 21. 1986. 01v. of Safety Research, National Institute for Occupa-
tional Safety and Health (NIOSH). Morgantown. UV. Govt. Rep. Announce.
Index. 18: 809.
0275d -58- 11/15/89
-------
Atkinson. R. 1985. Kinetics and mechanisms of the reactions of the
hydroxyl radicals with organic compounds In the gas phase. Chem. Rev. 85:
69-201.
Avlado. O.M. and M.A. BeleJ. 1974. Toxlclty of aerosol propellants on the
respiratory and circulatory systems. I. Cardiac arrhythmia 1n the mouse.
Toxicology. 2: 31-42.
Avlado, O.M. and D.G. Smith. 1975. Toxlclty of aerosol propellants In the
respiratory and circulatory systems. VIII. Respiration and circulation In
primates. Toxicology. 3: 241-252.
BeleJ, H.A., O.G. Smith and'O.K. Avlado. 1974. Toxlclty of aerosol propel-
lants 1n" the respiratory and curculatory systems. IV. Cardlotoxlclty In the
monkey. Toxicology. 2: 381-395.
Blake, O.A. and G.H. Hergner. 1974. Inhalation studies on the blotrans-
formatlon and elimination of *4C-tr1chlorofluormethane and l*C-d1chloro-
fluoromethane In beagles. Toxlcol. Appl. Pharmacol. 30: 396-407.
Blohm, H., H. Braun, P. Kaschny. H. Schlll, B. Jastorff and H. 01ehl. 1985.
Subacute toxlclty of 1,1 ,l-tr1chloroethane, noise and their combination In
rats. Ecotoxlcol. Environ. Saf. 10(3): 295-301.
Borchers, R.. P. Fabian, B.C. Krueger, et al. 1987. CFC-113
(CCI-F-CCIF.) In the stratosphere. Planet. Space Sc1. 35: 657-663.
0275d
.59. 11/15/89
-------
Brodzlnsky. R. and H.B. Singh. 1982. Volatile organic chemicals In the
atmosphere: An assessment of available data. In: Handbook of Chemical
Property Estimation Methods. Environmental Behavior of Organic Compounds.
W.J. Lyman. W.F. Reehl and O.H. Rosenblatt. Ed. McGraw-Hill Book Co.. New
York. NY. p. 184.
Busey, H.M. 1967. Unpublished data. Hazleton Laboratories. Falls Church.
VA, sponsored by Haskell Lab.. Ou Pont Co.. Wilmington, OE. (Cited In
ACGIH. 1986)
Bysshe, S.E. 1982. Bloconcentratlon factor In aquatic organisms, in:
Handbook for Chemical Property Estimation Methods. Environmental Behavior
of Organic Compounds, U.J. Lyman. Vi.F. Reehl. O.H. Rosenblatt. Ed.
McGraw-Hill Book Co.. New York. NY. p. 5-1. 5-5.
Carter. V.L.. P.M. Chlkos. J.O. MacEwen and K.C. Back. 1970. Effects of
Inhalation of Freon 113 on Laboratory Animals. NTIS AO 727524. p. 309-325.
Chemllne. 1989. Chemical Information System (CIS). On-line: April 3. 1989.
Chlou, C.T.. L.J. Peters and V.H. Freed. 1979. A physical concept of soil-
water equilibrium for nonlonlc organic compounds. Science. 206: 831-832.
Chou. C.C.. R.J. Mllsteln. U.S. Smith. H. Vera Ruiz. M.J. Molina and F.S.
Rowland. 1978. Stratospheric photodlssodatlon of several saturated
perhalochlorofluorocarbon compounds In current technological use (Fluoro-
carbons -13, -113, -114, and -115). J. Phys. Chen. 82: 1-7.
0275d -60- 11/15/89
-------
Chrostek, W.J. 1980. Health Hazard Evaluation Report No. HHE-80-072-787 at
Fischer and Porter Company, Warmlnster. Pennsylvania. Olv. of Surveillance.
Hazard Evaluations and Field Studies. NIOSH. Cincinnati. OH. 12 p.
Clark. O.G. and O.J. Tlnston. 1973. Correlation of the cardiac sensitizing
potential of halogenated hydrocarbons with their physlcochemlcal properties.
Br. J. Phartn. 49: 355-357.
Clark, O.G. and D.J. Tlnston. 1982. Acute Inhalation toxlclty of. some
halogenated and non-halogenated hydrocarbons. Human Toxlcol. 1: 239-247.
Council on Environmental Quality. 1975. Fluorocarbons and the atmosphere.
National Science Foundation. Washington, DC.
Crockett, P.U.. 8. K1l1an. K.S. Crump and R.B. Howe. 1985. Descriptive
methods for using data from dissimilar experiments to locate a no-adverse-
toxlc-effects region 1n the dose-duration plane. Prepared by K.S. Crump and
Co.. Inc.. under Contract No. 68-01-6807 for the Environmental Criteria and
Assessment Office. U.S. EPA. Cincinnati. OH.
Desollle, H., L. Truffert, A. Bourgulgnon, P. Oelavlerre, N. PhUbert and C.
Glrard-Uallon. 1968. Etude Experimental de la ToxIcHe' de trlchlorotM-
pluoroethane (Freon 113). Arch. Mai. Prof. Hed. Trav. Secur. Soc. 29:
381-388. (Cited In U.S. EPA. 1983)
0275d -61- 11/15/89
-------
Dining, W.L.. S.J. Gonslor. G.U. Boggs and C.G. Hendoza. 1988. Organic
photochemistry 20: A method for estimating gas-phase rate constants for
reactions of hydroxyl radicals with organic compounds from their relative
rates of reaction with hydrogen peroxide under photolysis In I,l.2-tr1-
chlorotrlfluoroethane. Environ. Scl. Technol. 22: 1447-1453.
Du Pont de Nemours Co. 1980. Freon Product Information B-2. E.I. Ou Pont
de Nemours and Company, Wilmington, OE.
Durkln, P. and W. Meylan. 1988. User's Guide for 02PLOT: A Program for
Dose/Duration Graphs. Prepared by Chemical Hazard Assessment Division,
Syracuse Research Corporation under Contract No. 68-C8-0004 for the Environ-
mental Criteria and Assessment Office. U.S. EPA, Cincinnati. OH.
Ensmlnger. A. 1988. Sampling of organic pollutants In the workplace
atmosphere. Results. CAH Notes DOC. 131: 299-301. (Fre.)
Epstein. S.S.. E. Arnold. J. Andrea. W. Bass and Y. Bishop. 1972. Detec-
tion of chemical mutagens by the dominant lethal assay In the mouse.
Toxlcol. Appl. Pharmacol. 23: 288-325.
Fabian. P. 1986. Halogenated hydrocarbons In the atmosphere. In; Handbook
of Environmental Chemistry. Vol. 4, Part A. 0. Hutzlnger. Ed. Sprlnger-
Verlag, Berlin, p. 24-25, 42-43, 48-51.
•
Great Lakes Water Quality Board. 1983. An Inventory of Chemical Substances
Identified 1n the Great Lakes Ecosystem. Vol. 1: Summary. Great Lakes
Water Quality Board. Windsor, Ontario, p. 86.
0275d -62- 11/15/89
-------
Haskell Laboratory. 1968. Human Skin Absorption Studies with Trlchloro-
fluoroethane. Medical Research Project NBMR-10H (1968). Submitted by E.I.
du Pont de Nemours and Company to U.S. EPA, August, 1979. (Cited In U.S.
EPA, 1983}
Hawley, G.G. 1981. Condensed Chemical Dictionary, 10th ed. Von Nostrand
Relnhold, New York. p. 1043-1044.
Hazelton Laboratories, Inc. 1967a. Unpublished data of E.I. du Pont" de
Nemours and Company. HRO-1015, HLO-242. Final report. Teratology study 1n
rabbits. Submitted to U.S. EPA. August 20, 1979. (CUed In U.S. EPA. 1983}
Hazelton Laboratories, Inc. 1967b. Unpublished data of E.I. du Pont de
Nemours and Company. MR-1962-001. HLO-0258-67. Reproduction study 1n
rabbits. Submitted In U.S. EPA, August 20, 1979. (CUed In U.S. EPA, 1983)
Horvath. A.L. 1982. Halogenated Hydrocarbons: Solubility Mlsclblllty with
Water. Marcel Oekker Inc.. New York, NY. p. 499.
Howard. P.H., P.R. Durkln and A. Hanchett. 1975. Environmental Hazard
Assessment of One and Two Carbon Fluorocarbons. U.S. EPA, Office of Toxic
Substances. Washington. OC. EPA 560/2-75-003. p. 58-66.
Hubrlch, C. and F. Stahl. 1980. The ultraviolet absorption of some
halogenated methanes and ethanes of atmospheric Interest. 3. Photochem.
12: 93-107.
0275d -63- 11/15/89
-------
Imbus, H.R. and C. Adklns. 1972. Physical examinations of workers exposed
to trlchloroethane. Arch. Environ. Health. 24: 257-261.
Jones. C.J., B.C. Hudson, P.J. McGugan and A.J. Smith. 1978. The leaching
of some halogenated organic compounds from domestic waste. J. Hazard. Hat.
2: 227-233.
Khalll, M.A.K. and R.A. Rasmussen. 1988. The global trends and mass
balance of F-113. Chera. Geol. 70(1-2): 99.
Lee. S. and 0. Parkinson. 1982. Health Hazard Evaluation Report No. HETA
80-168-1204. Rola-Esmark Company. DuBols, Pennsylvania. Prepared for NIOSH.
Cincinnati. OH. 30 p.
Lehmann, £.. J. Gmehllng and U. UeldHch. 1986. Survey on organic solvents
In various products and methods for estimating workplace exposures. In_:
Safety and Health Aspects of Organic Solvents, V. Rllhlmakl and U.
Ulfvarson. Ed. Alan R. Uss. Inc.. New York. NY. p. 31-41.
Longstaff. E. 1988. Carcinogenic and mutagenlc potential of several
fluorocarbons. Ann. NY Acad. Sc1. 534: 283-298.
Lyman, W.J. 1982. Environmental behavior of organic compounds. In.:
Handbook of Chemical Property Estimation Methods. U.J. Lyman. U.F. Reehl and
O.H. Rosenblatt. Ed. McGraw-Hill Book Co.. New York. NY. p. 4-9.
0275d -64- 11/15/89
-------
Mabey, W. and T. Mill. 1978. Critical review of hydrolysis of organic
compounds In water under environmental conditions. J. Phys. Chem. Ref.
Data. 7: 383-403.
Mahurln, R.G. and R.L. Bernstein. 1988. Fluorocarbon-enhanced mutagensls
of polyaromatlc hydrocarbons. Environ. Res. 45(1): 101-107.
Maklde. Y., T. Tomlnaga and F.S. Rowland. 1979. Gas chromatographlc analy-
sis of halogenated hydrocarbons \n air over Japan. Chem. Lett. 4: 355-358.
Mantel, N. and M.A. Schnelderman. 1975. Estimating 'isafe levels." a
hazardous undertaking. Cancer Res. 35: 1379.
May. O.C. and M.J. Blotzer. 1984. A report of occupational deaths
attributed to fluorocarbon-113. Arch. Environ. Health. 39(5): 352-354.
McOuffle, B. 1981. Estimation of octanol/water partition coefficients for
organic pollutants using reverse-phase HPLC. Chemosphere. 10: 73-83.
MUhaelson. J.B. and D.J. Huntsman. 1964. Oral toxlclty of l,2,2-tr1-
chloro-l,l.2-tr1fluoroethane. J. Med. Chem. 7: 378-379. (Cited In ACGIH.
1986; U.S. EPA. 1983)
MITRE. 1988. Database, 7th update. U.S. EPA, Washington, DC.
Morgan, A., A. Black, M. Walsh and D.R. Belcher. 1972. The absorption and
retention of Inhaled MuoMnated hydrocarbon vapours. Int. J. Appl. Radlat.
Isot. 23(6): 285-291.
0275d -65- 11/15/89
-------
Mullln. U.S.. A. Azar. C.I. Relnhardt. P.E. Smith and E.F. Fabryka. 1971.
Halogenated hydrocarbon Induced cardiac arrhythmias associated with released
of endogenous eplnephrlne. Unpublished report of Haskell Laboratory, E.I.
Oupont de Nemours and Company. MR1262. HL-279-71. Submitted to U.S. EPA.
(Cited In U.S. EPA. 1983)
NIOSH (National Institute for Occupational Safety and Health). 1988.
National Occupational Exposure Survey (NOES). NIOSH. Cincinnati. OH.
On-line: 5/10/88.
OSHA (Occupational Safety and Health Administration). 1989. Air Contami-
nants. Final Rule. 29 CFR Part 1910. Federal Register. 54(12): 2540.
Otson. R. 1987. Purgeable brganlcs In Great Lakes raw and treated water.
Int. J. Environ. Anal. Chen. 31: 41-53.
Parrlsh. C.F. 1983. Solvents, Industrial, in: Klrk-Othmer's Encyclopedia
of Chemical Technology. Vol. 21. 3rd ed. John HI ley and Sons. Inc.. New
York. p. 380. 400.
PelUzzaM. E.O.. T.O. Hartwell. B.S.H. Harris. R.O. Waddell. O.A. UhUaker
and H.O. Erlckson. 1982. Purgeable organic compounds In mother's milk.
Bull. Environ. Contan. Toxlcol. 28: 322-328.
Plell, J.D., K.O. Oliver and U.A. HcClenny. 1988. Ambient air anaylses
using nonspecific flame lonlzatlon and electron capture detection compared
to specific detection by mass spectroscopy. J. Air Pollut. Control Assoc.
38: 1006-1010.
0275d -66- 11/15/89
-------
Raffl, G.B. and F.S. Vlolante. 1981. Freon 113 neurotoxlc? A case report.
Int. Arch. Occup. Environ. Health. 49: 125-127.
Rasmus sen, K. and S. Sabroe. 1986. Neuropsychologlcal symptoms among metal
workers exposed to halogenated hydrocarbons. Scand. J. Soc. Hed. H(3):
161-168.
Rasmussen, K.. H.J. Jeppesen and P. Arllen-Soborg. 1988. Psychoorganlc
syndrome from exposure to fluorocarbon-113: An occupational disease. Eur.
Neurol. 28(4): 205-207.
•1
Relnhardt. C.F. and H.E. Maxfleld 1973. Eplnephrlne-lnduced cardla
arrhythmia potential of some common Industrial solvents. J. Occup. Hed.
15(12): 953-955.
Relnhardt. C.F.. A. Azar, H.E.. HaxHed, P.F. Smith and L.S. Hullln. 1971a.
Cardiac arrhythmias and aerosol "sniffing.* Arch. Environ. Health. 2:
265-278.
Relnhardt. C.F.. H. Mclaughlin. H.E. Haxfleld, L.S. Hullln and P.E. Smith.
1971D. Human exposure to fluorocarbon 113. Am. Ind. Hyg. Assoc. J. 32(3):
143-152.
Sabel. G.V. and T.P. Clark. 1984. Volatile organic compounds as Indicators
of municipal sold waste leachate contamination. Waste Hanage. Res. 2:
119-130.
0275d -67- 11/15/89
-------
Savolalnen, H. and P. PfaffH. 1980. Dose-dependent neurochemlcal effects
of I,1.2-tr1ch1oro-l,2.2-tr1f1uoroethane Inhalation exposure In rats.
Toxlcol. Lett. (Amst). 6(1): 43-50.
Simmon, V.F., K. Kauhanen and G. Tardlff. 1977. Mutagenlc activity of
chemicals Identified In drinking water. Oev. Toxlcol. Environ. Sd. 2:
249-258.
Smart, B.E. 1980. Fluorine compounds, organic, In: Klrk-Othmer's Encyclo-
pedia of Chemical Technology. Vol. 10. 3rd ed. John Wiley and Sons. Inc..
•i
New York. p. 856-866. V
SRI (Stanford Research Institute). 1988. 1988 Directory of Chemical
Producers: United States of America. SRI International. Kenlo Park. CA.
p. 1033.
Steinberg. H.. R.E. Boldt. R.A. Renne and H.H. Weeks. 1969. Inhalation
Toxlclty of 1.1.2-Tr1chloro-l,2,2-TMfluoroethane (TCTFE). Army Environ-
mental Hygiene Agency. Edgewood Arsenal. HO. 24 p.
Stopps, G.J. and H. Mclaughlin. 1967. Psychophys1olog1cal testing of human
subjects exposed to solvent vapors. Am. Ind. Hyg. Assoc. J. 28(1): 43-50.
Swann, R.L., O.A. Laskowskl. O.A. NcCall. K. Vanderkuy and O.G. Olshburger.
1983. A rapid method for the estimation of the environmental parameters
octanol/water partition coefficient, soil sorptlon constant, water to air
ratio, and water solubility. Res. Rev. 85: 17-28.
0275d -68- 11/15/89
-------
Thomas. R.G. 1982. Volatilization from water. In: Handbook of Chemical
Property Estimation Methods. Environmental Behavior of Organic Compounds.
McGraw-Hill Book Co.. New York. MY. p. 15-1 to 15-34.
Troch1mow1cz, H.J., A. Azar, J.B. Terrlll and L.S. Mullln. 1974. Blood
levels of fluorocarbon related to cardiac sensltlzatlon: II. Am. Ind. Hyg.
Assoc. J. 35(10): 632-639.
Trochlmowlcz, H.J., G.M. Rusch, T. Ch1u and C.K. Wood. 1988. Chronic
Inhalation toxlclty/carclnogenlclty study In rats exposed to fluorocarbon
113 (FC-113). Fund. Appl. Toxlcol. 11(1): 68-75.
U.S. EPA. 1980. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water, Criteria
Documents. Federal Register. 45(231): 79347-79357
U.S. EPA. 1983. Health Assessment Document for 1.1,2-trlchloro-l,2,2-trl-
fluoroethane. (Chlorofluorocarbon CFC-113). Office of Health and Environ-
mental Assessment, Environmental Criteria and Assessment Office. Research
Triangle Park, NC. EPA 600/8-82-002F. NTIS PB84-118843.
U.S. EPA. 1984. Methodology and Guidelines for Ranking Chemicals Based on
Chronic Toxldty Data. Prepared by the Office of Health and Environmental
Assessment. Environmental Criteria and Assessment Office. Cincinnati. OH for
the Office of Emergency and Remedial Response. Washington, DC.
0275d -69- 11/15/89
-------
U.S. EPA. 1986*. Methodology for Evaluating Reportable Quantity Adjust-
ments Pursuant to CERCLA Section 102. Prepared by the Carcinogen Assessment
Group, Office of Health and Environmental Assessment for the Office of
Emergency and Remedial Response. Washington. DC.
U.S. EPA. 1986b. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1987. Graphical Exposure Modeling System (GEMS). CLOGP3. U.S.
EPA. Washington. OC.
U.S. EPA. 1989. Integrated ' Risk Information System (IRIS). Online.
Office of Health and Environmental Assessment. Environmental Criteria and
Assessment Office, Cincinnati. OH.
•
U.S. EPA/OWRS (U.S. Environmental Protection Agency/Office of Water Regula-
tions and Standards). 1986. Guidelines for Deriving Numerical National
Water Quality Criteria for the Protection of Aquatic Organisms and Their
Uses. U.S. EPA. Washington. OC. p. 22-58. 98. PB85-227049/XAB.
USITC (U.S. International Trade Commission). 1988. Synthetic Organic
Chemicals. U.S. Production and Sales. 1987. USITC Publ. 2118. Washington.
DC. p. 15-30.
Valnlo, H., J. Nickels and T. Helnonen. 1980. Dose-related hepatotoxldty
of I,l,2-tr1ch1oro-l,2,2-tr1fluoroethane 1n short-term Intermittent Inhala-
tion exposure In rats. Toxicology. 18(1): 17-26.
0275d -70- 11/15/89
-------
Verschueren. K. 1983. Handbook of Environmental Data on Organic Compounds,
2nd ed. Van Nostrand Relnhold Co.. New York. p. 1147.
Ward, R. 1983. E.I. du Pont de Nemours and Company. TransmHtal of
Summary of Teratogenld ty Study of 1,1,2-trlchloro-l,2,2-trlfluoroethane 1n
Rats. Report Number CTL/P/731. Imperial Chemical Industries, Central
Toxicology Laboratory, England. February 17, 1983. (Cited In U.S. EPA,
1983}
Weststat, Inc. and Midwest Research Institute. 1987. Household Solvent
Products: A "Shelf" Survey with Laboratory Analysis. U.S. EPA, Washington,
DC. EPA-OTS 560/5-87-006.
Zakharl. S. and O.H. Avlado. 1982. Cardiovascular toxicology of aerosol
propellants, refrigerants and related solvents. In.: Cardiovascular
Toxicology, E.W. Van Stee, Ed. Raven Press, New York. p. 281-314.
0275d -71- 11/15/89
-------
APPENDIX A
LITERATURE SEARCHED
This HEED 1s based on data Identified by computerized literature
searches of the following:
CHEHLINE
TSCATS
CASH online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXLIT
TOXLIT 65
RTECS
OHM TAGS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic)
HSOB
SCISEARCH
Federal Research In Progress
These searches were conducted In April, 1989. and the following secondary
sources were reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices. Sth ed. Cincinnati. OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1987. TLVs: Threshold Limit Values for Chemical Substances In the
Work Environment adopted by ACGIH with Intended Changes for
1987.1988. Cincinnati. OH. 114 p.
Clayton. G.O. and F.E. Clayton. Ed. 1981. Patty's Industrial
Hygiene and Toxicology. 3rd rev. ed.. .Vol. 2A. John U1ley and
Sons, NY. 2878 p.
Clayton. G.O. and F.E. Clayton. Ed. 1981. Patty's Industrial
Hygiene and Toxicology. 3rd rev. ed.. Vol. 2B. John Wiley and
Sons. NY. p. 2879-3816.
0275d -72- 11/15/89
-------
Clayton, 6.D. and F.E. Clayton. Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed.. Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
Grayson. M. and D. Eckroth, Ed. 1978-1984. Klrk-Othmer Encyclo-
pedia of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc.. Littleton, MA. 575 p.
IARC (International Agency for Research on Cancer). IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. IARC. WHO, Lyons. France.
Jaber, H.H., W.R. Habey, A.T. L1eu, T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
EPA 600/6-84-010. NTIS PB84-243906. SRI International. Menlo
Park. CA.
NTP (National Toxicology Program). 1987. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co.. NY.
SRI (Stanford Research Institute). 1987. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report In the Special Review
Program, Registration Standards Program and the Data Call In
Programs. Registration Standards and the Data Call 1n Programs.
Office of Pesticide Programs, Washington, DC.
USITC (U.S. International Trade Commission). 1986. Synthetic
Organic Chemicals. U.S. Production and Sales, 1985, USITC Publ.
1892, Washington. DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals. 2nd ed. Van Nostrand Relnhold Co.. NY.
Wlndholz. H.. Ed. 1983. The Merck Index,'10th ed. Merck and Co.,
Inc.. Rahway, NJ.
Worthing. C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
0275d -73- 11/15/89
-------
In addition, approximately 30 compendia of aquatic toxlclty data were
reviewed. Including the following:
Battelle's Columbus Laboratories. 1971. Uater Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and H.T. Flnley. 1980. Handbook of Acute Toxlclty
of Chemicals to Fish and Aquatic Invertebrates. Summaries of
Toxlclty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Oept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington. OC.
McKee. J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California. State Water
Quality Control Board. Publ. No. 3-A.
Plmental. 0. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, OC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs. U.S.
EPA. Washington. OC. EPA 540/9-79-003. NTIS PB 80-196876.
0275d -74- 11/15/89
-------
o
IS)
in
l
APPENDIX B
Suomary lable for l,l,2-lrtchloro-1.2.2-trtfluoroethane
Species
Inhalation Exposure
Subchrontc rat
Chronic rat
Carclnogentclty 10
Oral Exposure
Subchrontc rat
Chronic rat
Carclnogentctty 10
BE PORTABLE QUANTITIES
Based on Chronic Toxlctty:
Based on Carctnogenlclty:
Exposure
10.000 ppM (76.618 Mg/M*)
6 hours/day. S days/week
for 24 Months
10.000 ppM (J6.638 Mg/a>)
6 hours/day. S days/week
for 24 Months
10
10.000 ppM (76. (38 Mg/M*)
6 hours/day. S days/week
for 24 Months
10.000 ppM (76.638 Mg/M*)
6 hours/day. S days/week
for 24 Months
10
5000
10
Effect
decreased body weight relative
to controls In feules; observed
also In Males at higher exposure
concentration
decreased body weight relative
to controls In feMles; observed
also In Males at higher exposure
concentration
10
decreased body weight relative
to controls In feMales; observed
also In Males at higher exposure
concentration
decreased body weight relative
to controls In feMles; observed
also In Males at higher exposure
concentration
10
HfO or qj* Reference
27 Mg/M* TrochlMowlci
et al., 1988
27 Mg/M* TrochlMowlci
et al.. 1988
10 ID
3 Mg/kg/day TrochlMowlci
et al., 1988
3 Mg/kg/day TrochlMowlci
et al., 1988
10 10
Trochlaowlci
et al.. 1988
ID - Insufficient data
in
>x
00
-------
APPENDIX C
DOSE/DURATION RESPONSE GRAPHS FOR EXPOSURE TO
1.1.2-TRICHLORO-1.2.2-TRIFLUOROETHANE
C.I. DISCUSSION
Oose/durat1on-response graphs for Inhalation exposure to I,l,2-tr1-
chloro-l,2.2-tr1fluoroethane generated by the method of Crockett et al.
(1985) using the computer software by Durkln and Meylan (1988) developed
under contract to ECAO-C1nc1nnat1 are presented In Figures C-1 and C-2.
Data used to generate these graphs are presented In Section C.2. In the
generation of these figures, all responses are classified as adverse (PEL.
AEL or LOAEL) or nonadverse (NOEL or NOAEL) for plotting. For Inhalation
exposure, the ordlnate expresses concentration as the experimental concen-
tration expressed as mg/ra» multiplied by the time parameters of the expo-
sure protocol (e.g.. hours/day and days/week) and Is presented, as expanded
experimental concentration [expanded exp cone (mg/m>)]. For oral expo-
sure, the ordlnate expresses dose as human equivalent dose. The animal
dose. In mg/kg/day Is multiplied by the cube root of the ratio of the
animal:human body weight to adjust for species differences In basal
metabolic rate (Mantel and Schnelderman. 197S). The result Is then
multiplied by 70 kg. the reference human body weight, to express the human
equivalent dose as mg/day for a 70 kg human.
The boundary for adverse effects (solid line) 1s drawn by Identifying
the lowest adverse effect dose or concentration at the shortest duration of
exposure at which an adverse effect occurred. From this point, an Infinite
line 1s extended upward* parallel to the dose axis. The starting point Is
then connected to the lowest adverse effect dose or concentration at the
next longer duration of exposure that has an adverse effect dose or concen-
tration equal to or lower than the previous one. This process 1s continued
0275d -76- 11/15/89
-------
n
\
»
If* • !•
r»
•23
Fl«
nil
N13
K3
••••••I 9.999
t 9.9*1 *.9l
NUWN WUI¥ MMTION
.1
-Ml
_l
1 t
f - FEL
L - LOAEL
n . NOAEL
N . NOEL
A . AEL
FIGURE C-1
Oose/Ouratlon-Response Graph for Inhalation Exposure to
l,1.2-Tr1chloro-l,2.2-tMfluoroethane (Envelope Method)
0275d
-77-
11/15/89
-------
H
C
U
«.Mt
NUIMM RU1W MMTIOM «tl«« It !>*»•«>
r»
F . PEL
L • LOAEL
n . NOAEL
N - NOEL
A . AEL
FIGURE C-2
Oose/Durat1on-Response Graph for Inhalation Exposure to
1J,2-Tr1ch1oro-1.2.2-tr1f1uoroethane (Censored Envelope Method)
02754
-78-
11/15/89
-------
to the lowest adverse effect dose or concentration. From this point, a line
1s extended to the right, parallel to the duration axis. The region of
adverse effects lies above the adverse effects boundary.
Using the envelope method, the boundary for no adverse effects (dashed
line) 1s drawn by Identifying the highest no adverse effects dose or concen-
tration. From this point, a line parallel to the duration axis 1s extended
to the dose or concentration axis. The starting point Is then connected to
the next lower or equal no adverse effect dose or concentration at a longer
duration of exposure. When this process can no longer be continued, a line
1s dropped parallel to the dose or concentration axis to the duration axis.
The no adverse effects region lies below the no adverse effects boundary.
At either ends of the graph between the adverse effects and no adverse
effects boundaries are regions of ambiguity. The area (1f any) resulting
from Intersection of the adverse effects and no adverse effects boundaries
Is defined as the region of contradiction.
In the censored data method, all no adverse effect points located In the
region of contradiction are dropped from consideration and the no adverse
effect boundary Is redrawn so that It does not Intersect the adverse effects
boundary and no region of contradiction Is generated. This method results
In the most conservative definition of the no adverse effects region.
The graph 1n Figure C-l was generated using the envelope method. The
adverse effects boundary Is defined by four data points: the LOAEL for
Impaired psychomotor function (Stopps and Mclaughlin, 1967) In humans
exposed to 2500 ppra for 2 hours (Rec. f24); two LOAELs for reversible CNS
effects observed during 5-hour exposures (Steinberg et al., 1969) of dogs to
13,000 ppm (Rec. |18) and of rats to 11,000 ppra (Rec. f!7); and the LOAEL
for decreased body weight In female rats (Rec. f2) exposed to 2000 ppm 6
0275d -79- 11/15/89
-------
hours/day, 5 days/week for 2 years (Trochlmowlcz et al., 1988). The no
adverse effects boundary In Figure C-l Is defined by: NOELs for body weight
decreases In dogs (Rec. #9} and mice (Rec. #10} from the 2-week Inhalation
study by Carter et al. (1970); NOELs for body weight decreases in dogs (Rec.
15) and In rats (Rec. 17) from a 4-week study (Steinberg et al., 1969); a
NOAEL (Rec. 14) for physical examinations of occupationally exposed workers
(Imbus and Adklns. 1972); and the NOEL for weight decreases In rats (Rec.
|1) from the 2-year study by Trochlmowlcz et al. (1988). A region of
contradiction Is defined In Figure C-1. The rat data (Recs. #1, 2) from the
study by Trochlmowlcz et al. (1988) were the basis for the chronic RfO for
Inhalation exposure derived In Chapter 8. The region of contradiction
disappears In Figure C-2, In which Recs. 19 and 5 are not Included In the
defining of the no adverse effects boundary.
C.2. DATA USED TO GENERATE GRAPH
Chemical Name: 1,1,2-TMchloro-l ,2.2tr1fluoroethane
CAS Number: 76-13-1
Document Title: Health and Environmental Effects Document for 1,1,2-TM-
chloro-1,2,2-trlfluoroethane
Document Number: pending
Document Date: pending
Document Type: HEED
RECORD fl:
Species
Sex:
Effect:
Route:
Number
Number
: Rats
Both
NOEL
Inhalation
Exposed:
Responses:
200
0
Dose:
Duration Exposure:
Duration Observation:
2737.000
24.0 months
24.0 months
Type of Effect:
Site of Effect:
Severity Effect: 3
Comment: Concentrations studied: 2000. 10,000, 20,000 ppm 6 hours/day,
S days/week. See following record.
Citation: Trochlmowlcz et al.. 1988
0275d
-80-
11/15/89
-------
RECORD f2:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
Female
LOAEL
Inhalation
Number Exposed: 100
Number Responses: NR
Type of Effect: WGTDC
Site of Effect: BODY
Severity Effect: 4
Dose:
Duration Exposure:
Duration Observation:
13685.000
24.0 months
24.0 months
See previous record.
higher concentration.
Decreased body weight gain In males at
Troch1mow1cz et al.. 1988
RECORD 13:
Species: Rats
Sex: Hale
Effect: NOEL
Dose: 511.000
Duration Exposure: 84.0 days
Duration Observation: 84.0 days
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
6
0
1
Comment: Experimental concentration: 200 ppm 8 hours/day. No
treatment-related changes In liver, kidney or body weights,
urinary catecholamlne metabolites or liver cytochrome P-450.
Citation: 81 ohm et al.. 1985
RECORD |4:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Humans
Male
NOEL
Inhalation
Dose: 957.000
Duration Exposure: 2.8 years
Duration Observation: 2.8 years
Number Exposed: 50
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 4
•
Occupational exposure study: workers averaged 2.8 years (6
hours/day,5 days/week) In rooms with mean concentration of
699 ppm (cone, range-46-4700 ppm). No adverse effects In
physical examinations.
Imbus and Adklns, 1972
0275d
-81-
11/15/89
-------
RECORD IS:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Dogs
Both
NOEL
Inhalation
Dose: 6980.000
Duration Exposure: 4.0 weeks
Duration Observation: 4.0 weeks
Number Exposed: 0
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 3
Experimental concentration: 5100 ppm 6 hours/day, 5 days/
week. No adverse effects on body weight, organ weights,
macro or microscopic exam of major organs.
Steinberg et al., 1969
RECORD *6:
Species
Sex
Effect:
Route:
Number
Number
: Guinea pigs
Female
NOEL
Inhalation
Exposed: 10
Responses: 0
Dose:
Duration Exposure:
Duration Observation:
6980.000
4.0 weeks
4.0 weeks
Comment:
Citation:
Type of Effect:
Site of Effect:
Severity Effect: 3
See record |5.
Steinberg et al.. 1969
RECORD |7:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
Both
NOEL
Inhalation
Dose: 6980.000
Duration Exposure: 4.0 weeks
Duration Observation: 4.0 weeks
Number Exposed: 20
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 3
See record 15. Also, no effects on
voluntary movement on activity wheel.
Steinberg et al.. 1969
rotobar performance and
027 5d
-82-
11/15/89
-------
Dose:
Duration Exposure:
Duration Observation:
15328.000
14.0 days
14.0 days
RECORD 18: Species: Monkeys
Sex: NR
Effect: NOEL
Route: Inhalation
Number Exposed: 4
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 3
Comment: Experimental concentration: 2000 ppm continuous exposure. No
significant changes In hematology, clinical chemistry, EEG,
body or organ weights.
Citation: Carter et al.t 1970
RECORD 19:
Species: Dogs
Sex: NR
Effect: NOEL
Dose:
Duration Exposure:
Duration Observation:
15328.000
14.0 days
14.0 days
Route: Inhalation
Number Exposed:
Number Responses:
8
0
Comment:
Citation:
Type of Effect:
Site of Effect:
Severity Effect:
See record 18.
Carter et al., 1970
RECORD |10:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Mice
NR
NOEL
Inhalation
Dose: 15328.000
Duration Exposure: 14.0 days
Duration Observation: 14.0 days
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
See record *8.
Carter et al., 1970
40
0
027 5
-------
RECORD |11:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
NR
NOEL
Inhalation
Number Exposed: 0
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 3
See record f8.
Carter et al., 1970
Oose: 15328.000
Duration Exposure: 14.0 days
Duration Observation: 14.0 days
RECORD 112:
Species:
Sex:
Effect:
Route:
Rats
Hale
NOAEL
Inhalation
Dose:
Duration
Duration
Exposure:
Observation:
2737.000
2.0 weeks
2.0 weeks
Number Exposed: NR NR
Number Responses: NR NR
Type of Effect: ENZYH HISTO
Site of Effect: LIVER LIVER
Severity Effect: 1 3
Comment: Concentrations: 200. 1000. 2000 ppm 6 hours/day. S days/week.
Altered enzyme activity; light microscopy no effects;
electron microscopy slight to moderate changes In endoplasmlc
retlculum In liver cells.
Citation: Valnlo et al.. 1980
RECORD 113:
Comment:
Citation:
Species: Rats
Sex: . Hale
Effect: NOEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
See record #12.
Valnlo et al., 1980
Oose: 274.000
Duration Exposure: 2.0 weeks
Duration Observation: 2.0 weeks
NR
0
0275d
-84-
11/15/89
-------
RECORD |14:
Species: Mice
Sex: NR
Effect: PEL
Route: Inhalation
Dose:
Duration Exposure:
Duration Observation:
728061.000
1.0 days
1.0 days
Comment:
Citation:
RECORD |15:
Comment:
Citation:
RECORD 116:
Comment:
Citation:
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Two-hour LC5Q value > 95000 ppm.
Oesollle et al.. 1968
Species: Guinea pigs Dose:
Sex: NR Duration Exposure:
Effect: FEL Duration Observation:
Route: Inhalation
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Two-hour LC5Q value - 120,000 ppm.
Desollle et al.. 1968
Species: Rats Dose:
Sex: NR Duration Exposure:
Effect: FEL Duration Observation:
Route: Inhalation
Number Exposed: NR
Number Responses: NR
Type of Effect: DEATH
Site of Effect: BODY
Severity Effect: 10
Two-hour LC5Q value - 110.000 ppm.
Oesollle et al.. 1968
919656.000
1 .0 days
1 .0 days
843018.000
1 .0 days
1.0 days
0275d
-85-
11/15/89
-------
RECORD
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
NR
LOAEL
Inhalation
Dose: 21075.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
Number Exposed: NR
Number Responses: NR
Type of Effect: BEHAV
Site of Effect: CNS
Severity Effect: 7
Reversible CNS effects observed during 6-hour exposure to
11,000 ppm.
Steinberg et al.. 1969
RECORD |18: Species: Dogs
Sex: NR
Effect: LOAEL
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
NR
NR
BEHAV
.CNS
7
Dose: 24907.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
Comment: Reversible CNS effects observed during 6-hour exposure to
13.000 ppm.
Citation: Steinberg et al.. 1969
RECORD 119:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Humans
Hale
FEL
Inhalation
Dose:
Duration Exposure:
Duration Observation:
980967.000
1.0 days
1.0 days
Number Exposed: 1
Number Responses: 1
Type of Effect: DEATH
Site of Effect: CAROV
Severity Effect: 10
Occupational accident report. Worker exposed to about 128.000
ppn for less than 45 minutes dfed due to cardiac arrest.
Hay and Blotzer. 1984
0275d
-86-
11/15/89
-------
RECORD 120:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Dogs
NR
LOAEL
Inhalation
Dose: 38319.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
Number Exposed: 29
Number Responses: 10
Type of Effect: FUND
Site of Effect: CAROV
Severity Effect: 7
Cardiac arrhythmias observed In unanesthetlzed dogs given
Injections of eplnephrlne with 10-mlnute exposure to 5000
ppm, "cardiac sensltlzatlon.11
Relnhardt et al., 1973
RECORD 121:
Species:
Sex:
Effect:
H1ce
NR 7
LOAEL '*•
Dose:
Duration
Duration
Exposure:
Observation:
766380.000
1.0 days
1 .0 days
Route: Inhalation
Comment:
Citation:
Number Exposed: 3
Number Responses: 3
Type of Effect: FUND
SHe of Effect: CARDV
Severity Effect: 7
Cardiac arrhythmias In anesthetized mice given 6-m1nute
exposure to 100,000 ppm and Injections of eplnephrlne.
Avlado and Belej. 1974
RECORD 122: Species: Dogs
Sex: NR
Effect: AEL
Dose: 76638.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:
NR
NR
FUND
CARDV
7
Comment:
Citation:
£€50 value of 10.000 ppm for
eplnephrlne: S-m1nute exposure.
Clark and Tlnston. 1973
cardiac sensltlzatlon to
0275d
-87-
11/22/89
-------
RECORD 123:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Monkeys
NR
AEL
Inhalation
Number Exposed: NR
Number Responses: NR
Type of Effect: FUND
Site of Effect: CAROV
Severity Effect: 7
Dose:
Duration Exposure:
Duration Observation:
191595.000
1.0 days
1.0 days
Five-minute exposures
arrhythmias, myocardlal
exogenous eplnephrlne.
BeleJ et al.. 1974
to 25,000 ppm caused cardiac
depressions and tachycardia without
RECORD 124: Species: Humans
Sex: Hale
Effect: LOAEL
Dose: 19160.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
Route: Inhalation
Number Exposed:
Number Responses:
Type of Effect:
Site of Effect:
Severity Effect:
2
2
MOTOR
CNS
7
Comment: Impaired psychomotor function during 2-hour exposure to
concentrations at or above 2500 ppm.
Citation: Stopps and Mclaughlin. 1967
RECORD 125:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Humans
Male
NOEL
Inhalation
Dose: 11496.000
Duration Exposure: 1.0 days
Duration Observation: 1.0 days
Number Exposed: 2
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 7
See Record |24.
Stopps and Mclaughlin. 1967
0275d
.88-
11/15/89
-------
RECORD #26:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Humans
Hale
NOEL
Inhalation
Dose: 992.000
Duration Exposure: 2.0 weeks
Duration Observation: 2.0 weeks
Number Exposed: 4
Number Responses: 0
Type of Effect:
Site of Effect:
Severity Effect: 4
Exposure protocol: 500 ppm, 6 hours/day, 5 days/week for 1
week, then 1000 ppm, 6 hours/day. 5 days/week for 1 week.
Estimated dose Is average expanded cone. No effects on
psychomotor function or physical exam.
Relnhardt et al., 1971b
NR . Not reported
0275d
-89-
11/15/89
------- |