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    Concise International Chemical Assessment Document 11






    1,1,1,2-Tetrafluorethane







    First draft prepared by

    Mrs P. Barker and Mr R. Cary, Health and Safety Executive, Liverpool,
    United Kingdom,
    and
    Dr S. Dobson, Institute of Terrestrial Ecology, Huntingdon, United
    Kingdom




    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization, and produced within the framework of the
    Inter-Organization Programme for the Sound Management of Chemicals.

    World Health Organization Geneva, 1998

         The International Programme on Chemical Safety (IPCS),
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    sound management of chemicals in relation to human health and the
    environment.

    WHO Library Cataloguing in Publication Data

    1,1,1,2-Tetrafluoroethane.

    (Concise international chemical assessment document ; 11)

    1.Hydrocarbons, Fluorinated - adverse effects 
    2.Hydrocarbons, Fluorinated - toxicity
    3.Occupational exposure 4.Dose-response relationship, Drug
    I.International Programme on Chemical Safety 
    II.Series

    ISBN 92 4 153011 1  (NLM Classification: QD 341.H9)
    ISSN 1020-6167

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    TABLE OF CONTENTS

    FOREWORD

    1. EXECUTIVE SUMMARY

    2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES

    3. ANALYTICAL METHODS

    4. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    5. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

    6. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         6.1. Environmental levels
         6.2. Human exposure

    7. COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS
         

    8. EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

         8.1. Single exposure
         8.2. Irritation and sensitization
         8.3. Short-term exposure
         8.4. Long-term exposure
              8.4.1. Subchronic exposure
              8.4.2. Chronic exposure and carcinogenicity
         8.5. Genotoxicity and related end-points
         8.6. Reproductive and developmental toxicity
         8.7. Immunological and neurological effects

    9. EFFECTS ON HUMANS

    10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

    11. EFFECTS EVALUATION

         11.1. Evaluation of health effects
              11.1.1. Hazard identification and dose-response assessment
              11.1.2. Criteria for setting guidance values for 1,1,1,2-tetrafluoroethane
              11.1.3. Sample risk characterization
         11.2. Evaluation of environmental effects

    12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    13. HUMAN HEALTH PROTECTION AND EMERGENCY ACTION

         13.1. Human health hazards
         13.2. Advice to physicians
         13.3. Spillage

    14. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    INTERNATIONAL CHEMICAL SAFETY CARD

    REFERENCES

    APPENDIX 1 - SOURCE DOCUMENT

    APPENDIX 2 - CICAD PEER REVIEW

    APPENDIX 3 - CICAD FINAL REVIEW BOARD

    RÉSUMÉ D'ORIENTATION

    RESUMEN DE ORIENTACION
    

    FOREWORD

         Concise International Chemical Assessment Documents (CICADs) are
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         The primary objective of CICADs is characterization of hazard and
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    upon which the CICAD has been based.

         Risks to human health and the environment will vary considerably
    depending upon the type and extent of exposure. Responsible
    authorities are strongly encouraged to characterize risk on the basis
    of locally measured or predicted exposure scenarios. To assist the
    reader, examples of exposure estimation and risk characterization are
    provided in CICADs, whenever possible. These examples cannot be
    considered as representing all possible exposure situations, but are
    provided as guidance only. The reader is referred to EHC 1701 for
    advice on the derivation of health-based guidance values.


                   

    1 International Programme on Chemical Safety (1994)
     Assessing human health risks of chemicals: derivation of guidance
    values for health-based exposure limits. Geneva World Health
    Organization (Environmental Health Criteria 170)

         While every effort is made to ensure that CICADs represent the
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    the scientific literature to the date shown in the executive summary.
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    Procedures

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    FIGURE 1

    1.  EXECUTIVE SUMMARY

         This CICAD on 1,1,1,2-tetrafluoroethane was based on a review of
    human health concerns (primarily occupational) prepared by the United
    Kingdom Health and Safety Executive in 1995 (Standring el al., 1995).
    Additional information on effects on human health and the environment
    was identified in ECETOC (1995). Data identified up to December 1994
    were covered by these reviews. Additional data identified after these
    reviews were published have been incorporated as appropriate.
    Information on the nature of the peer review and availability of the
    source document is presented in Appendix 1. Information on the peer
    review of this CICAD is presented in Appendix 2. This CICAD was
    approved as an international assessment at a meeting of the Final
    Review Board, held in Berlin, Germany, on 26-28 November 1997.
    Participants at the Final Review Board meeting are listed in Appendix
    3. The International Chemical Safety Card (ICSC 1281) for
    1,1,1,2-tetrafluoroethane, produced by the International Programme on
    Chemical Safety (IPCS, 1998), has also been reproduced in this
    document.

         1,1,1,2-Tetrafluoroethane (CAS no. 811-97-2) is a gaseous
    fluorocarbon that is manufactured by the reaction of hydrogen fluoride
    with trichloroethylene in a closed system. It is used primarily as a
    refrigerant for "high-temperature" refrigeration, such as domestic
    refrigerators and automobile air conditioners. Other potential uses
    include application in plastic foam blowing, as a solvent for special
    cleaning applications, as an aerosol propellant for medical inhalers,
    and as a fire extinguishant in place of halons.

         Little information was identified on exposure of the general
    public or workers to 1,1,1,2-tetrafluoroethane. During its manufacture
    in the United Kingdom, employee exposure to the chemical was very low,
    with no measured concentrations above 7 ppm (29.2 mg/m3).  There are
    no exposure measurements from its use in the manufacturing industry
    and no data on the exposure of field servicing personnel. The
    situation in the workplace in the United Kingdom and analogous data
    from a single study of exposure to dichlorotrifluoroethane (HCFC 123)
    would suggest that exposure to 1,1,1,2-tetrafluoroethane in the
    workplace is normally low (i.e., below 10 ppm [41.7 mg/m3]), with
    occasional short-term peak exposures of up to several hundred parts
    per million

         Information on the effects of 1,1,1,2-tetrafluoroethane on humans
    is limited to one report; most available data on the toxicological
    effects of 1,1,1,2-tetrafluoroethane have been derived from studies
    conducted with laboratory animals. 1,1,1,2-tetrafluoroethane exhibits
    relatively low toxicity. A reduction in maternal body weight gain in
    rabbits exposed to 40 000 ppm (166 800 mg/m3)
    1,1,1,2-tetrafluoroethane and signs of delayed fetal development in
    rats following exposure of the dams to 50 000 ppm (208 500 mg/m3)
    1,1, 1,2-tetrafluoroethane have been noted in developmental toxicity
    studies. In other toxicological investigations, adverse health effects

    have not been observed following exposure to concentrations up to
    10 000 ppm (41 700 mg/m3). The weight of evidence for carcinogenicity
    is limited to an increased incidence of Leydig cell adenomas following
    exposure to 50 000 ppm (208 500 mg/m3), and 1,1,1,2-tetrafluoroethane
    has not been found to be genotoxic in studies conducted to date.

         The low toxicity of 1,1,1,2-tetrafluoroethane to the few aquatic
    organisms tested as well as its high volatility indicate negligible
    risk to aquatic organisms.

         Atmospheric effects have been assessed by modelling. Recent
    observations have shown a rapid increase in atmospheric concentrations
    of 1,1,1,2-tetrafluoroethane, mainly as a result of emissions over the
    past decade. Modelling indicates insignificant ozone depiction
    potential, a significant global warming potential, and negligible
    acidification potential.

    2.  IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES

         1,1,1,2-Tetrafluoroethane (CAS no. 811-97-2; C2H2F4;
    1,2,2,2-tetrafluoroethane, HFC 134a, HFA 134a, HCFC 134a) is a gaseous
    fluorocarbon with a faint ether-like odour. It is soluble in alcohols,
    esters, and chlorinated solvents, but it is only slightly soluble in
    water. It has a boiling point of -26°C and a vapour pressure of 630
    kPa at 25°C. Additional properties are presented in the International
    Chemical Safety Card reproduced in this document. The conversion for
    1,1,1,2-tetrafluoroethane is 1 ppm=4.17 mg/m3 (at 25°C). The
    structural formula for 1,1,1,2-tetrafluoroethane is:

                                           F   H
                                           '   '
                                       F - C - C - F
                                           '   '
                                           F   H

    3.  ANALYTICAL METHODS

         An unpublished method based on a Health and Safety Executive
    (1995) procedure has been used to monitor exposure to 
    1,1,1,2-tetrafluoroethane. The sample is collected diffusively onto
    Spherocarb and analysed by thermal desorption into a gas chromatograph
    fitted with a flame ionization detector (FID). The diffusive uptake
    rate is reported as 1.2 ng/ppm per minute, and the method has been
    validated down to 0.1 ppm for exposure periods of 30-480 min.1 Pumped
    sampling onto Anasorb CMS followed by solvent desorption and analysis
    with a gas chromatograph fitted with an FID has also been validated
    (Griffiths, 1998), Both the Miran infrared monitor (Quantitech Ltd)2
    and the Innova 1312 photoacoustic monitor (CBISS)3 can be used to
    measure airborne concentrations of 1,1,1,2-tetrafluoroethane to
    sub-ppm concentrations.

         There are no published methods for the biological monitoring of
    occupational exposure to 1,1,1,2-tetrafluoroethane. However, by
    analogy with other haloalkanes, it may be possible to develop
    biological monitoring methods based on the analysis of
    1,1,1,2-tetrafluoroethane in the breathing zone or urine (Woollen et
    al., 1990, 1992). In addition, a study of its use in medical inhalers
    revealed that 1,1,1,2-tetrafluoroethane can be measured in blood
    samples; sampling at 2 min indicated 1,1,1,2-tetrafluoroethane levels
    of 200-700 ng/ml, with a substantial reduction by 12 min (Donnell et
    al., 1995).


                   

    1 Personal communication, ICI Laboratories, The Heath, Runcorn, UK.

    2 Unit 3, Old Wolverton Road, Old Wolverton, Milton Keynes, UK
    MK12 5NP.

    3 5-11 Coronation Drive, Bromborough, Wirral, UK L62 3LF.

    4.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         1,1,1,2-Tetrafluoroethane is manufactured by the reaction of
    hydrogen fluoride with trichloroethylene in a closed system. It is
    available as a liquefied gas and is supplied in a variety of
    pressurized containers. 1,1,1,2-tetrafluoroethane is used primarily as
    a refrigerant for "high-temperature" refrigeration, such as domestic
    refrigerators and automobile air conditioners. Other potential uses
    include application in plastic foam blowing, as a solvent for special
    cleaning applications, as an aerosol propellant for medical inhalers,
    and as a fire extinguishant in place of halons.

         Between 1990 and 1995, the estimated global production of 
    1,1,1,2-tetrafluoroethane for dispersive use increased from 0.2 to 73.8
    kilotonnes per year; over this same period, the estimated global
    release of this chemical increased from 0.1 to 20.3 kilotonnes per
    year (AFEAS, 1996).

    5. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

         1,1,1,2-Tetrafluoroethane is expected to partition almost
    exclusively to the atmosphere. Aqueous discharges would be expected to
    volatilize, with half-lives of days to a few weeks. It is not expected
    that 1,1,1,2-tetrafluoroethane will accumulate in biota (log Kow
    approx. 1.06) or adsorb to soil or sediment (log Koc approx. 1.5).
    The atmospheric equilibrium concentration in cloud water has been
    estimated at less than 0.2 ppt by weight based on predicted
    atmospheric concentrations of 100-200 ppt by volume (0.4-0.8 µg/m3)
    for the year 2020 (McCulloch, 1993). The long atmospheric half-life
    will result in more or less uniform distribution in the atmosphere on
    a global scale (Franklin, 1993),

         The overall estimated lifetime of 1,1,1,2-tetrafluoroethane in
    the troposphere is 14.6 years (IPCC, 1995); degradation is initiated
    by hydroxyl (OH) radicals. It is theoretically possible that 
    1,1,1,2-tetrafluoroethane could contribute to ozone depletion by means 
    of CF3Ox, radicals arising from the atmospheric degradation of
    tetrafluoroethane; however, this contribution has been estimated to be
    insignificant in recent studies (Ko et al., l994; Ravishankara et al.,
    1994).

         1 1,1,2-Tetrafluroethane's global warming potential over a
    100-year time horizon (relative to carbon dioxide) has been estimated
    at 1300, compared with 3800 for CFC-11 and 8100 for CFC-12, for which
    1,1,1,2-tetrafluoroethane is the main substitute (IPCC, 1995).
    Franklin (1993) has estimated that 1,1,1,2-tetrafluoroethane will
    reach an atmospheric background concentration of 100 ppt by volume
    (0.4 µg/m3) by 2010-2020 and will then be responsible for only about
    0.3% of the radiative forcing due to all anthropogenic greenhouse
    gases present in the atmosphere.

         Hydroxyl radicals break down 1,1,1,2-tetrafluoroethane to form
    the CF3CHFO radical, which reacts with oxygen to generate
    trifluoroacetyl fluoride (CF3COF) or undergoes cleavage to give
    formyl fluoride (HCOF) and the CF3 radical, which is ultimately
    converted to carbonyl fluoride (COF2) and hydrogen fluoride (HF).
    Modelling studies predict that 40% of 1,1,1,2-tetrafluoroethane
    breakdown will proceed via the former route and 60% by the latter
    route (Franklin, 1993). Recent research suggests that the yield of
    trifluoroacetyl fluoride is in the range of 7-20% rather than 40%, as
    was previously assumed (Wallington et al., 1996).

         The principal fate of the acid fluorides (CF3COF, HCOF, and
    COF2) will be uptake by cloud water and hydrolysis to trifluoroacetic
    acid, formic acid, carbon dioxide, and hydrogen fluoride. Dry
    deposition to ocean or land surfaces may occur to a limited extent and
    will be followed by hydrolysis (AFEAS, 1992, 1993).

         The contribution of degradation products to environmental
    fluorides and acidity of rainwater is expected to be negligible (WMO,
    1989; Franklin, 1993).

         There are no known natural sources of trifluoroacetic acid.
    However, recent work (Frank et al., 1996) has measured trifluoroacetic
    acid in rainwater and surface waters in Europe and Israel at levels
    too high to be explained by the atmospheric degradation of
    1,1,1,2-tetrafluoroethane and other chlorofluorocarbon substitutes.
    The origin of this trifluoroacetic acid is currently unexplained, and
    a natural source cannot be ruled out. Using the same assumptions for
    emission and atmospheric degradation as above (Franklin, 1993),
    deposition of trifluoroacetic acid in rainwater would be 45 kilotonnes
    per year (in the years 2010-2020), with an average concentration in
    precipitation globally at 0.1 µg/litre. Trifluoroacetic acid will
    partition into the aqueous environment; assuming accumulation in the
    upper levels of seawater, an increased concentration of 1.5 ng/litre
    would be expected for each 100 kilotonnes of 1,1,1,2-tetrafluoroethane
    degraded.

         Laboratory tests have demonstrated no appreciable degradation of
    1,1,1,2-tetrafluoroethane in activated sludge (Tobeta, 1989) or by the
    methanotropic bacterium  Methylosimus trichosporium (DeFlaun et al.,
    1992). Trifluoroacetic acid can be degraded under anoxic conditions to
    trifluoromethane, inorganic fluoride, methane, and carbon dioxide
    (Visscher et al., 1994).

    6.  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    6.1  Environmental levels

         In 1995, the average atmospheric concentration of 
    1,1,1,2-tetrafluoroethane was about 2 ppt (8.3 ng/m3);
    there had been a significant increase in concentration measured
    throughout 1994 and 1995, rising from about 0.3 ppt (1.3 ng/M3) in
    early 1994 to a range of 1.2-3.4 ppt (5.0-14.2 ng/m3) in late 1995
    (Montzka et al., 1996). Measurements were taken on land in Canada, the
    continental United States, Hawaii, American Samoa, and Tasmania and at
    sea in the Pacific and Atlantic oceans.

    6.2  Human exposure

         Information on potential exposure of the general public to 
    1,1,1,2-tetrafluoroethane was not identified, and there are limited 
    data concerning occupational exposure. During its manufacture in the 
    United Kingdom in a modern plant, employee exposure was very low, with 
    no measured concentrations above 7 ppm (29.2 mg/m3) (Standring et 
    al., 1995). There are no exposure measurements from its use in the
    manufacturing industry and no data on the exposure of field servicing
    personnel. At the time of review, there was only one manufacturer in
    the United Kingdom, although other production facilities are envisaged
    to come on stream in the near future. The situation in the United
    Kingdom and analogous data from a single study of exposure to
    dichlorotrifluoroethane (HCFC 123) (Standring et al., 1995) would
    suggest that exposure is normally low (i.e., below 10 ppm [41.7
    mg/m3], 12-hour time-weighted average), with occasional short-term
    peak exposures of up to several hundred parts per million (H. Sibley,
    undated).

    7.  COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND 
    HUMANS

         The elimination and distribution of a single breath inhalation of
    [18F] 1,1,1,2-tetrafluoroethane were measured in a small group of
    volunteers using whole body gamma-counting (Pike et al., 1995).
    Distribution was extensive, and elimination was rapid and essentially
    complete within 6 h (half-life approx. 1.5-4 h). Elimination of
    radioactivity in the urine was observed in some but not all subjects,
    and there was no evidence of accumulation.

         A group of four volunteers received 16 breath inhalations of 1,
    1,1,2-tetrafluoroethane (total dose 1200 mg) over a 10-min period in
    an investigation of its use as a propellant in medical devices (Monte
    et al., 1994). Urine samples were collected over a 24-h period and
    analysed for trifluoroacetic acid using 19F nuclear magnetic
    resonance spectroscopy (detection limit 10 ng/ml). The amounts of
    trifluoroacetic acid measured in urine ranged from undetectable to
    0.0004% of the administered 1,1,1,2-tetrafluoroethane. There were no
    1,1,1,2-Tetrafluoroethane other fluorinated products detected in urine
    using this technique.

         In two inhalation studies conducted with rats,
    1,1,1,2-tetrafluoroethane was poorly absorbed (Ellis el al., 1991,
    1993), and elimination was rapid and achieved mainly by exhalation of
    unchanged 1,1,1,2-tetrafluoroethane (Finch et al., 1995). Very little
    metabolism occurred, with the main metabolite being carbon dioxide;
    trifluoroacetic acid was identified in urine. There was no significant
    accumulation of absorbed 1,1,1,2-tetrafluoroethane in specific
    tissues.

    8.  EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

    8.1  Single exposure

         1,1,1,2-Tetrafluoroethane has low acute toxicity. An approximate
    4-h lethal concentration of 567 000 ppm (2.36 ×  106 mg/m3) has been
    reported for rats; no effects were observed at 81 000 ppm (337 770
    mg/m3) (Kennedy, 1979a, as cited in ECETOC, 1995). At concentrations
    in excess of 200 000 ppm (834 000 mg/m3), exposure to 
    1,1,1,2-tetrafluoroethane depressed the central nervous system of 
    rats.1 Anaesthetic effects have also been observed in other species. 
    Cardiac sensitization (an increased sensitivity of the heart) to 
    exogenous adrenalin has been observed in dogs exposed to 
    1,1,1,2-tetrafluoroethane, with a no-observed-effect level (NOEL) of 
    40 000 ppm (166 800 mg/m3) (Hardy el al., 1991).

    1 Programme for Alternative Fluorocarbon Testing, presentation at
    Toulouse International Toxicology Forum, September 1989; meeting notes
    presented as a personal communication to P Standring, 1993.

    8.2  Irritation and sensitization

         Studies on irritation or sensitization were not available.

    8.3  Short-term exposure

         Information from typical short-term repeated exposure toxicity
    studies was not identified.

    8.4  Long-term exposure

    8.4.1  Subchronic exposure

         No significant exposure-related toxicological effects were
    observed in an inhalation study in which groups of male and female
    rats were exposed for 13 weeks to 1,1,1,2-tetrafluoroethane at
    concentrations up to 50 000 ppm (208 500 mg/m3) (Hext, 1989; Collins
    el al., 1995),

    8.4.2  Chronic exposure and carcinogenicity

         In a study conducted according to a contemporary protocol, groups
    of 85 male and 85 female Wistar-derived Alderley Park rats were
    exposed (whole-body) to 0 (air only), 2500, 10 000, or 50 000 ppm (0,
    10 425, 41 700, or 208 500 mg/m3) 1,1,1,2-tetrafluoroethane, 6 h/day,
    5 days/week, for 2 years (Hext & Parr-Dobrzanski, 1993; Collins el
    al., 1995). Mortality rates were low and similar in the control and
    exposed groups. No exposure-related pathological findings were
    recorded at interim sacrifice (52 weeks). At termination, the only
    exposure-related pathological findings were increased incidences of
    Leydig (interstitial) cell hyperplasia and benign Leydig cell adenomas
    in the testes. The microscopic findings in the testes occurred mainly
    in animals surviving to the end of the study. In the control, 2500,

    10 000, and 50 000 ppm (0, 10 425, 41 700, or 208 500 mg/m3) groups,
    the incidence of Leydig cell hyperplasia was 27/85, 25/79, 31/85, and
    40/85 (32, 32, 36, and 47%), respectively; the incidence of Leydig
    cell adenoma was 9/85, 7/79, 12/85, and 23/85 (11, 9, 14, and 27%),
    respectively. Hyperplasia was observed in most animals with such
    tumours. At 50 000 ppm (208 500 mg/m3) 1,1,1,2-tetrafluoroethane, the
    incidence of Leydig cell adenoma was significantly (p < 0.05)
    increased above the controls. The incidence of Leydig cell adenomas
    and hyperplasia at 10 000 ppm (41 700 mg/m3) was within the
    historical control levels observed at this laboratory; from 1985 to
    1995, the background incidence of this tumour ranged between 4 and
    19%. The no-observed-adverse-effect level (NOAEL) in this study is
    considered to be 10 000 ppm (41 700 mg/m3).

         Other studies were less rigorously performed, but no
    exposure-related neoplastic or non-neoplastic effects were observed in
    2-year inhalation studies (1 -h daily nose-only exposure) at
    concentrations up to 50 000 ppm (208 500 mg/m3) in rats and up to
    75 000 ppm (312 750 mg/m3) in mice (Alexander el al., 1995a) or in 
    a similarly designed 1 - year study in which dogs were exposed to 
    120 000 ppm (500 400 mg/m3) 1,1,1,2-tetrafluoroethane (Alexander el 
    al., 1995b).

    8.5  Genotoxicity and related end-points

         The genotoxic potential of 1,1,1,2-tetrafluoroethane has been
    investigated in several well-conducted studies (bacterial mutagenicity
    [Ames] test, an  in vitro mammalian cell cytogenetics study, an 
     in vivo chromosomal aberration assay, a micronucleus study, an 
     in vivo unscheduled DNA synthesis assay, and a dominant lethal
    study). 1,1,1,2-Tetrafluoroethane was not genotoxic in any of the
    tests (Anderson & Richardson, 1979; Hodge et al., 1979; Longstaff et
    al., 1984; Müller & Hofmann, 1989; Callander & Priestley, 1990;
    Mackay, 1990; Trueman, 1990; Collins et al., 1995).

    8.6  Reproductive and developmental toxicity

         No exposure-related effects were observed in a standard fertility
    study in which groups of rats were exposed to 0, 2500, 10 000, or 
    50 000 ppm (0, 10 425, 41 700, or 208 500 mg/m3)
    1,1,1,2-tetrafluoroethane, 1 h/day during gametogenesis, mating, and
    post-mating (Alexander et al., 1996). The results from a dominant
    lethal study revealed no effect on fertility in male rats (Hodge et
    al., 1979). In a standard developmental toxicity study in rats,
    delayed fetal development (a statistically significant reduction in
    mean fetal weight, delayed ossification of digits) was observed when
    the dams were exposed to 50 000 ppm (208 500 mg/m3)
    1,1,1,2-tetrafluoroethane; no significant exposure-related effects
    were observed at 10 000 ppm (41 700 mg/m3) (Hodge et al., 1980). No
    other exposure-related developmental effects were observed in rats at
    levels up to 40 000 ppm (166 800 mg/m3) 1,1,1,2-tetrafluoroethane, a
    concentration causing decreased maternal body weight gain in rabbits

    (Wickramaratne, 1989; Collins et al., 1995). In the study with
    rabbits, there was a 30% reduction during exposure with subsequent
    recovery, resulting in a net reduction in body weight of 3% compared
    with controls.

    8.7  Immunological and neurological effects

         Based upon the available evidence, specific immunological or
    neurological effects associated with long-term exposure to 
    1,1,1,2-tetrafluoroethane were not identified.

    9.  EFFECTS ON HUMANS

         Limited data are available from an investigation into the use of
    1,1,1,2-tetrafluoroethane as a propellant in a metered-dose inhaler
    (Donnell et al., 1995). Volunteers received up to 16 breath
    inhalations of 1,1,1,2-tetrafluoroethane within about 10 min.
    Investigations included blood pressure and heart rhythm, limited blood
    biochemistry, and pulmonary function tests; no abnormalities were
    observed, and there were no clinical signs of toxicity.

    10.  EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

         1,1,1,2-Tetrafluoroethane has no significant effect on the growth
    of the bacterium  Pseudomonas putida (6-h EC50 >730 mg/litre)
    (Coleman & Thompson, 1990). Acute toxicity to freshwater organisms is
    low ( Daphnia magna, 48-h EC50 980 mg/litre; rainbow trout
     Oncorhynchus mykiss, 96-h LC50 450 mg/litre) (Stewart & Thompson,
    1990; Thompson, 1990). The high aqueous concentrations used in these
    studies can only be maintained artificially. In the environment, there
    would be rapid partitioning to the air compartment from the aqueous
    phase; the high concentrations used in the studies could be reached
    only if the atmosphere above the water were entirely
    1,1,1,2-tetrafluoroethane. Additional data on toxicity of
    1,1,1,2-tetrafluoroethane to aquatic or terrestrial organisms were not
    identified.

    11.  EFFECTS EVALUATION

    11.1  Evaluation of health effects

    11.1.1  Hazard identification and dose-response assessment

         Information on the effects of 1,1,1,2-tetrafluoroethane on humans
    is limited to one report; most available data on the toxicological
    effects of 1,1,1,2-tetrafluoroethane have been derived from studies
    conducted with laboratory animals. 1,1,1,2-Tetrafluoroethane exhibits
    relatively low toxicity. This chemical is a gas, appears to be
    essentially non-reactive, and is unlikely to be either an irritant or
    a sensitizer, although appropriate studies were not identified. A
    reduction in maternal body weight gain in rabbits exposed to 40 000
    ppm (166 800 mg/m3) 1,1,1,2-tetrafluoroethane and signs of delayed
    fetal development in rats following exposure of the dams to 50 000 ppm
    (208 500 mg/m3) 1,1,1,2-tetrafluoroethane have been noted in
    developmental toxicity studies. In other toxicological investigations,
    adverse health effects have not been observed following exposure to
    concentrations up to 10 000 ppm (41 700 mg/m3)
    1,1,1,2-tetrafluoroethane.

         The weight of evidence for carcinogenicity of
    1,1,1,2-tetrafluoroethane is limited. A statistically significant,
    exposure-related increase in the incidence of benign Leydig cell
    adenomas was observed in Wistar-derived rats exposed to a very high
    concentration (50 000 ppm [208 500 mg/m3]) of
    1,1,1,2-tetrafluoroethane for 2 years. However, the spontaneous
    incidence of these tumours is high in this and other strains of rats,
    and 1,1, 1,2-tetrafluoroethane has not been found to be genotoxic in
    studies conducted to date.

    11.1.2  Criteria for setting guidance values for
    1,1,1,2-tetrafluoroethane

         Based upon the available data, no adverse effects have been
    observed in laboratory animals exposed to 10 000 ppm (41 700 mg/m3)
    1,1,1,2-tetrafluoroethane. This value can therefore serve as a basis
    for comparison with estimated exposure for risk characterization,
    either with application of appropriate uncertainty factors or
    directly. Examples of both approaches are presented in section 11.1.3.

    11.1.3  Sample risk characterization

         The scenario chosen as an example is the occupational environment
    within the United Kingdom, where, under the current conditions of use,
    anticipated occupational exposure (8- or 12-h time-weighted average)
    to 1,1,1,2-tetrafluoroethane is in the vicinity of 10 ppm (41.7
    mg/m3), with occasional short-term peak exposures of up to several
    hundred parts per million. These concentrations are 1-3 orders of
    magnitude less than the NOAEL of 10 000 ppm (41 700 mg/m3) derived
    from toxicological studies conducted with laboratory animals. However,
    data on exposure in occupational circumstances within the United

    Kingdom are limited, and it is difficult to anticipate exposure
    conditions for other countries.

         A health-based occupational exposure limit for
    1,1,1,2-tetrafluoroethane of 1000 ppm (4170 mg/m3) (8-h time-weighted
    average) has been established within the United Kingdom. This equates
    to division of the NOAEL of 10 000 ppm (41 700 mg/m3) by an
    uncertainty factor of 10.

    11.2  Evaluation of environmental effects

         The low toxicity of 1,1,1,2-tetrafluoroethane to the few aquatic
    organisms tested as well as its high volatility indicate negligible
    risk to aquatic organisms.

         Atmospheric effects have been assessed by modelling. Recent
    observations have shown a rapid increase in atmospheric concentrations
    of 1,1,1,2-tetrafluoroethane, mainly as a result of emissions over the
    past decade. Modelling indicates insignificant ozone depletion
    potential, a significant global warming potential, and negligible
    acidification potential.

    12.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

         Previous evaluations of 1,1,1,2-tetrafluoroethane by
    international bodies were not identified. Information on international
    hazard classification and labelling is included in the International
    Chemical Safety Card reproduced in this document.

    13.  HUMAN HEALTH PROTECTION AND EMERGENCY ACTION

         Human health hazards, together with preventative and protective
    measures and first aid recommendations, are presented in the
    International Chemical Safety Card (ICSC 1281) reproduced in this
    document.

    13.1  Human health hazards

         1,1,1,2-Tetrafluoroethane is essentially non-toxic and flammable.
    There is a possibility of frostbite if the liquefied gas is released
    rapidly.

    13.2  Advice to physicians

         Symptomatic treatment and supportive therapy should be provided
    as indicated. Adrenaline and similar sympathomimetic drugs should be
    avoided following exposure, as cardiac arrhythmia may result, with
    possible subsequent cardiac arrest.

    13.3  Spillage

         In the event of spillage of 1,1,1,2-tetrafluoroethane, emergency
    crews should wear proper personal protection, including respiratory
    protection. Because the vapour is heavier than air, it may accumulate
    in lower spaces, causing a deficiency of oxygen. The oxygen content of
    the air should always be checked before the affected area is entered.

    14.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

         Information on national regulations, guidelines, and standards
    can be found in the International Register of Potentially Toxic
    Chemicals (IRPTC), available from UNEP Chemicals (IRPTC), Geneva.

         The reader should be aware that regulatory decisions about
    chemicals taken in a certain country can be fully understood only in
    the framework of the legislation of that country. The regulations and
    guidelines of all countries are subject to change and should always be
    verified with appropriate regulatory authorities before application.


        INTERNATIONAL CHEMICAL SAFETY CARD

                                                                                                                                           

    1,1,1,2-TETRAFLUOROETHANE                                                                      ICSC: 1281
                                                                                                   26.03.1998

    CAS#      811-97-2                                HFC 134a
    RTECS#    K18842500                               (cylinder)
    UN#       3159                                    C2H2F4

                                                      Molecular mass: 102.03
                                                                                                                                           

    TYPES OF HAZARD /   ACUTE HAZARDS /                         PREVENTION                          FIRST AID / FIRE FIGHTING
    EXPOSURE            SYMPTOMS
                                                                                                                                           

    FIRE                Not combustible. Gives off irritating   NO open flames.  NO contact with    In case of fire in the surroundings;
                        or toxic fumes (or gases) in a fire.    hot surfaces.                       all extinguishing agents allowed.

    EXPLOSION                                                                                       In case of fire: keep cylinder cool 
                                                                                                    by spraying with water.

    EXPOSURE

    Inhalation          Dizziness. Drowsiness. Dullness.        Local exhaust or breathing          Fresh air, rest. Refer for medical 
                                                                protection                          attention.

    Skin                ON CONTACT WITH LIQUID:                 Cold-insulating gloves.             ON FROSTBITE rinse with plenty of
                        FROSTBITE.                                                                  water, do NOT remove clothes.

    Eyes                                                        Safety goggles.

    Ingestion

    (continued)

                                                                                                                                           
    SPILLAGE DISPOSAL                                                          PACKAGING & LABELLING
                                                                                                                                           

    NEVER direct water jet on liquid. Do NOT let this chemical enter the       Symbol
    environment Chemical protection suit including self-contained breathing    R:
    apparatus.                                                                 S:
                                                                               UN Hazard Class: 2.2
                                                                               UN Subsidiary Risks:
                                                                               UN Pack Group:

                                                                                                                                           
    EMERGENCY RESPONSE                                                         STORAGE
                                                                                                                                           

    Transport Emergency Card TEC (R)-20G39                                     Fireproof. Keep in a well-ventilated room.

                                                                                                                                           
                                                      IMPORTANT DATA
                                                                                                                                           

    PHYSICAL STATE; APPEARANCE:                                 ROUTES OF EXPOSURE:
    COMPRESSED LIQUEFIED GAS, WITH CHARACTERISTIC ODOUR.        The substance can be absorbed into the body by inhalation.

    CHEMICAL DANGERS:                                           INHALATION RISK:
    On contact with hot surfaces or flames this substance       A harmful concentration of this gas in the air will be reached
    decomposes forming toxic and corrosive fumes.               very quickly on loss of containment.

    OCCUPATIONAL EXPOSURE LIMITS:                               EFFECTS OF SHORT-TERM EXPOSURE:
    TLV not established                                         Rapid evaporation of the liquid may cause frostbite. The
                                                                substance may cause effects on the central nervous system and
                                                                cardiovascular system, resulting in cardiac disorders.

    (continued)

                                                                                                                                           
                                                      PHYSICAL PROPERTIES
                                                                                                                                           

    Boiling point:                          -26°C
    Melting point:                          -101°C
    Solubility in water                     none
    Vapour pressure, kPa at 25°C:           630
    Relative vapour density (air = 1):      3.5
    0ctanolwater partition coefficient as log Pow: 1.06

                                                                                                                                           
                                                      ENVIRONMENTAL DATA
                                                                                                                                           

    Avoid release to the environment in circumstances different to normal use.

                                                                                                                                           
                                                             NOTES
                                                                                                                                           

    Do NOT use in the vicinity of a fire or a hot surface, or during welding. Turn leaking cylinder with the leak up to prevent escape of 
    gas in liquid state.

                                                                                                                                           
                                                      ADDITIONAL INFORMATION
                                                                                                                                           

    LEGAL NOTICE             Neither the CEC or the IPCS nor any person acting on behalf of the CEC or the IPCS is responsible
                             for the use which might be made of this information.
                                                                                                                                           
    

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    APPENDIX 1 - SOURCE DOCUMENT

    Standring et al. (1995)

         The draft report entitled 1,1,1,2-Tetrafluoroethane, Criteria
    document for an occupational exposure limit (prepared by P. Standring,
    S. Maidment, A. Ogunbiyi, J. Groves, and J. Cocker) was initially
    reviewed internally by a group of approximately 10 Health and Safety
    Executive experts (mainly toxicologists, but also experts in other
    relevant disciplines, such as epidemiology and occupational hygiene).
    The toxicology section of the amended draft was then reviewed by
    toxicologists from the United Kingdom Department of Health.
    Subsequently, the entire criteria document was reviewed by a
    tripartite advisory committee to the United Kingdom Health and Safety
    Commission, the Working Group for the Assessment of Toxic Chemicals
    (WATCH). This committee is composed of experts in toxicology and
    occupational health and hygiene from industry, trade unions, and
    academia.

         Members of the WATCH committee at the time of the peer review
    were Mr S. Bailey, Independent Consultant; Professor J, Bridges,
    University of Surrey; Dr I. Guest, Chemical Industries Association; Dr
    A. Hay, Trade Unions Congress; Dr L. Levy, Institute of Occupational
    Hygiene, Birmingham; Dr M. Molyneux, Chemical Industries Association;
    Mr A. Moses, Chemical Industries Association; Dr R. Owen, Trade Unions
    Congress; and Mr J. Sanderson, Independent Consultant.

    APPENDIX 2 - CICAD PEER REVIEW

         The draft CICAD on 1,1,1,2-tetrafluoroethane was sent for review
    to institutions and organizations identified by IPCS after contact
    with IPCS national Contact Points and Participating Institutions, as
    well as to identified experts. Comments were received from:

         Department of Health, London, United Kingdom

         Department of Public Health, Albert Szent-Gyorgyi University
         Medical School, Szeged, Hungary

         European Centre for Ecotoxicology and Toxicology of Chemicals
         (ECETOC), Brussels, Belgium

         Health Canada, Ottawa, Canada

         International Agency for Research on Cancer, Lyon, France

         Ministry of Health and Welfare, International Affairs Division,
         Government of Japan, Tokyo, Japan

         National Institute for Working Life, Solna, Sweden

         National Institute of Occupational Health, Budapest, Hungary

         United States Department of Health and Human Services (National
         Institute of Environmental Health Sciences)

         United States Environmental Protection Agency (Office of
         Pollution Prevention and Toxics, National Center for
         Environmental Assessment, Office of Research and Development;
         Office of Drinking Water)

    APPENDIX 3 - CICAD FINAL REVIEW BOARD

    Berlin, Germany, 26-28 November 1997

    Members

    Dr H. Ahlers, Education and Information Division, National Institute
    for Occupational Safety and Health, Cincinnati, OH, USA

    Mr R. Cary, Health Directorate, Health and Safety Executive, Bootle,
    United Kingdom

    Dr S. Dobson, Institute of Terrestrial Ecology, Huntingdon, United
    Kingdom

    Dr R.F Hertel, Federal Institute for Health Protection of Consumers &
    Veterinary Medicine, Berlin, Germany (Chairperson)

    Mr J.R. Hickman, Health Protection Branch, Health Canada, Ottawa
    Ontario, Canada

    Dr I. Mangelsdorf, Documentation and Assessment of Chemicals,
    Fraunhofer Institute for Toxicology and Aerosol Research, Hanover,
    Germany

    Ms M.E. Meek, Environmental Health Directorate, Health Canada, Ottawa,
    Ontario, Canada (Rapporteur)

    Dr K. Paksy, Department of Reproductive Toxicology, National Institute
    of Occupational Health, Budapest, Hungary

    Mr V. Quarg, Ministry for the Environment, Nature Conservation &
    Nuclear Safety, Bonn, Germany

    Mr D. Renshaw, Department of Health, London, United Kingdom

    Dr. J. Sekizawa, Division of Chemo-Bio Informatics, National Institute
    of Health Sciences, Tokyo, Japan

    Prof. S. Soliman, Department of Pesticide Chemistry, Alexandria
    University, Alexandria, Egypt (Vice-Chairperson)

    Dr M. Wallen National Chemicals Inspectorate (KEMI), Solna, Sweden

    Ms D Willcocks, Chemical Assessment Division, Worksafe Australia,
    Camperdown, Australia

    Dr M. Williams-Johnson, Division of Toxicology, Agency for Toxic
    Substances and Disease Registry, Atlanta, GA, USA

    Dr K. Ziegler-Skylakakis, Senatskommission der Deutschen
    Forschungsgemeinschaft zuer Pruefung gesundheitsschaedlicher
    Arbeitisstoffe, GSF-Institut fuer Toxikologie, Neutherberg,
    Oberschleissheim, Germany

    Observers

    Mrs B. Dinham,1 The Pesticide Trust, London, United Kingdom

    Dr R. Ebert, KSU Ps-Toxicology, Huels AG, Mart, Germany (representing
    ECETOC, the European Centre for Ecotoxicology and Toxicology of
    Chemicals)

    Mr R Green,1 International Federation of Chemical, Energy, Mine and
    General Workers' Unions, Brussels, Belgium

    Dr B. Hansen,1 European Chemicals Bureau, European Commission, Ispra,
    Italy

    Dr J. Heuer, Federal Institute for Health Protection of Consumers &
    Veterinary Medicine, Berlin, Germany

    Mr T. Jacob,1 DuPont, Washington, DC, USA

    Ms L. Onyon, Environment Directorate, Organisation for Economic
    Co-operation and Development, Paris, France

    Dr H.J. Weideli, Ciba Speciality Chemicals Inc., Basel, Switzerland
    (representing CEFIC, the European Chemical Industry Council)

    Secretariat

    Dr M. Baril, International Programme on Chemical Safety, World Health
    Organization, Geneva, Switzerland

    Dr R.G. Liteplo, Health Canada, Ottawa, Ontario, Canada

    Ms L. Regis, International Programme on Chemical Safety, World Health
    Organization, Geneva, Switzerland

    Mr A, Strawson, Health and Safety Executive, London, United Kingdom

    Dr P. Toft, Associate Director, International Programme on Chemical
    Safety, World Health Organization, Geneva, Switzerland


                   

    1 Invited but unable to attend.

    RÉSUMÉ D'ORIENTATION

         Ce CICAD relatif au 1,1,1,2-tétrafluoréthane est fondé sur une
    étude des problèmes de santé (notamment dans le domaine de l'hygiène
    du travail) réalisée par le Health and Safety Executive du Royaume-Uni
    en 1995 (Standring et al., 1995). Des informations complémentaires
    concernant les effets de cette substance sur la santé humaine et
    l'environnement ont été identifiées dans l'étude ECETOC (1995). Ces
    deux études prennent en compte les données antérieures à décembre
    1994. Les données postérieures à leur publication ont été incorporées
    dans le présent document. Les informations relatives à l'examen du
    document initial par les pairs et à sa disponibilité figurent à
    l'appendice 1. Les renseignements concernant l'examen du CICAD par les
    pairs font l'objet de l'appendice 2. Ce CICAD a été approuvé entant 
    qu'évaluation internationale lors d'une réunion du Comité d'évaluation
    finale qui s'est tenue à Berlin (Allemagne) du 26 au 28 novembre 1997.
    La liste des participants à cette réunion figure à l'appendice 3. La
    fiche d'information sur la sécurité chimique du 
    1,1,1,2-tétrafluoréthane (ICSC 128 1), établie parle Programme
    international sur la Sécurité chimique (IPCS, 1998), est également
    reproduite dans le présent document.

         Le 1,1,1,2-tétratluoréthane (CAS N° 811-97-2) est un
    fluorocarbure gazeux obtenu par réaction du fluorure d'hydrogène sur
    le trichloréthylène en vase clos. Il est utilisé principalement comme
    réfrigérant dans des appareils fonctionnant à température relativement
    élevée, comme les réfrigérateurs domestiques et les climatiseurs
    d'automobiles. Il peut également être employé dans la fabrication de
    mousses plastiques, comme solvant pour certaines opérations de
    nettoyage, comme propulseur d'aérosols pour inhalateurs médicaux, et
    comme produit extincteur à la place des halons.

         On dispose de peu d'informations sur l'exposition du grand public
    ou des travailleurs au 1,1,1,2-tétrafluoréthane, Le personnel employé
    à sa fabrication au Royaume-Uni a été soumis à une très faible
    exposition, les concentrations ne dépassant jamais 7 ppm (29,2
    mg/m3). L'exposition résultant de son utilisation dans l'industrie
    manufacturière n'a pas été mesurée et l'on ne dispose pas de données
    concernant l'exposition des personnels appelés à l'utiliser sur le
    terrain. Compte tenu de la situation sur les lieux de travail au
    Royaume-Uni, et par analogie avec les données obtenues lors d'une
    étude de l'exposition au dichlorotrifluoréthane (HCFC 123), il semble
    que la concentration de 1,1,1,2-tétratluoréthane sur les lieux de
    travail soit normalement faible (inférieure à 10 ppm, soit 41,7
    mg/m3), avec parfois des pies d'exposition de courte durée atteignant
    quelques centaines de parties par million.

         Les renseignements concernant les effets du 
    1,1,1,2-tétrafluoréthane sur l'homme se limitent à une étude; la plupart
    des données disponibles sur les effets toxicologiques de cette
    substance ont été obtenues à partir d'expériences chez l'animal. Le
    1,1,1,2-tétrafluoréthane a une toxicité relativement faible. Des
    études visant à évaluer sa toxicité pour le développement font état

    d'un ralentissement du gain pondéral chez des lapines exposées à
    40 000 ppm (166 800 mg/m3) et d'un retard de développement des foetus
    chez des rates exposées à 50 000 ppm (208 500 mg/m3). D'autres études
    toxicologiques ne signalent aucun effet défavorable chez des animaux
    exposés à des concentrations allant jusqu'à 10 000 ppm (41 700
    mg/m3). Les indices de cancérogénicité se limitent à une incidence
    accrue des adénomes des cellules de Leydig après exposition à 50 000
    ppm (208 500 mg/m3); d'autre part, les études menées jusqu'à présent
    ne révèlent aucun signe de génotoxicité,

         La faible toxicité du 1,1,1,2-tétrafluoréthane pour les quelques
    organismes aquatiques sur lesquels il a été testé et sa grande
    volatilité donnent à penser qu'il constitue un risque négligeable pour
    ces organismes.

         Les effets du 1,1,1,2-tétrafluoréthane sur l'atmosphère ont été
    évalués à l'aide de modèles. Des observations récentes ont révélé une
    augmentation rapide de sa concentration atmosphérique, résultant
    principalement des émissions qui ont eu lieu au cours de la dernière
    décennie. Les résultats de la modélisation montrent que le
    1,1,1,2-tétrafluoréthane présente un risque insignifiant en ce qui
    concerne la destruction de l'ozone, un risque significatif pour ce qui
    est du réchauffement mondial et un risque négligeable d'acidification.

    RESUMEN DE ORIENTACION

         Este CICAD (resumen de evaluación internacional de sustancias
    químicas) sobre el 1,1,1,2-tetrafluoroetano está basado en un estudio
    sobre su posible incidencia (fundamentalmente ocupacional) en la salud
    humana preparado por la Dirección de Salud y Seguridad del Reino Unido
    en 1995 (Standring et al., 1995), En el ECETOC (1995) se halló más
    información sobre los efectos en la salud humana y en el medio. Los
    datos manejados en esos dos estudios abarcan hasta diciembre de 1994.
    También se ha incluido cuando procedia información adicional hallada
    tras la publicación de esos estudios. En el apéndice 1 se informa
    sobre la naturaleza del examen colegiado y la disponibilidad del
    documento de base, y en el apéndice 2 se facilita información sobre el
    examen colegiado del presente resumen. Este CICAD fue aprobado como
    resumen de evaluación internacional en una reunión de la Junta de
    Revisión Final celebrada en Berlín (Alemania) los días 26 a 28 de
    noviembre de 1997. La lista de los participantes en la reunión de la
    Junta de Revisión Final figura en el apéndice 3. En este documento se
    reproduce también la ficha internacional de seguridad química (ICSC
    1281) para el 1,1,1,2-tetrafluoroetano, preparada por el Programa
    Internacional de Seguridad de las Sustancias Químicas (IPCS, 1998).

         El 1,1,1,2-tetrafluoroetano (CAS n° 811-97-2) es un fluorocarburo
    gaseoso que se fabrica haciendo reaccionar el ácido fluorhídrico y el
    tricloroetileno en un sistema cerrado. Se usa fundamentalmente como
    refrigerante para el enfriamiento de "alta temperatura," por ejemplo
    en los frigoríficos domésticos y en los sistemas de aire acondicionado
    de los automóviles. Otros usos posibles son su empleo en espumación,
    como disolvente en aplicaciones de limpieza especiales, como propulsor
    de aerosoles para inhaladores médicos y como extintor de incendios en
    lugar de los halones.

         La información hallada sobre la exposición del público general o
    los trabajadores al 1,1,1,2-tetrafluoroetano es escasa. Durante su
    fabricación en el Reino Unido, la exposición de los empleados a ese
    producto fue muy baja, y las concentraciones medidas no superaron en
    ningún caso las 7 ppm (29,2 mg/m3). No se dispone de datos sobre la
    exposición asociada a su uso en la industria fabril, ni sobre la
    exposición del personal de servicios sobre el terreno. La situación en
    los lugares de trabajo en el Reino Unido y otros datos análogos de un
    solo estudio de exposición al diclorotrifluoroetano (HCFC 123) parecen
    indicar que la exposición al 1,1,1,2-tetrafluoroetano en el lugar de
    trabajo es normalmente baja (es decir, inferior a 10 ppm [41,7
    mg/m3]), registrándose ocasionalmente exposiciones máximas breves de
    hasta varios cientos de partes por millón.

         Sólo hay un informe que trate de los efectos del
    1,1,1,2-tetrafluoroetano en el ser humano; la mayor parte de los datos
    disponibles sobre sus efectos toxicológicos proceden de estudios
    realizados en animales de laboratorio. El 1,1,1,2-tetrafluoroetano
    tiene una toxicidad relativamente baja. Los estudios sobre su
    toxicidad en el desarrollo han mostrado una reducción del aumento del

    peso corporal materno en conejos expuestos a 40 000 ppm (166 800
    mg/m3) de 1,1,1,2-tetrafluoroetano, así como signos de retraso del
    desarrollo fetal en ratas tras la exposición de las madres a
    concentraciones de 50 000 ppm (208 500 mg/m3). En otras
    investigaciones toxicológicas no se han observado efectos adversos
    para la salud tras la exposición a concentraciones de hasta 10 000 ppm
    (41 700 mg/m3). Los indicios de carcinogenicidad se limitan a un
    aumento de la incidencia de adenomas de las células de Leydig tras la
    exposición a 50 000 ppm (208 500 mg/m3), y no se han detectado
    efectos genotóxicos en los estudios realizados hasta la fecha.

         La baja toxicidad del 1,1,1,2-tetrafluoroetano para los escasos
    organismos acuáticos analizados, así como su elevada volatilidad,
    indican que el riesgo es insignificante para los organismos acuáticos.

         Se han elaborado modelos para evaluar los efectos atmosféricos.
    Observaciones recientes han puesto de manifiesto un rápido incremento
    de las concentraciones atmosféricas de 1,1,1,2-tetrafluoroetano,
    principalmente como resultado de las emisiones realizadas a lo largo
    del último decenio. La modelización ha revelado una desdeñable
    contribución potencial al agotamiento del ozono, una considerable
    capacidad de contribución al calentamiento mundial y un potencial de
    acidificación despreciable.
    


    See Also:
       Toxicological Abbreviations