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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY








    ENVIRONMENTAL HEALTH CRITERIA 172





    TETRABROMOBISPHENOL A and DERIVATIVES







    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.


    First draft prepared by Dr. G.J. van Esch,
    Bilthoven, Netherlands


    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization


    World Health Organization
    Geneva, 1995

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    WHO Library Cataloguing in Publication Data

    Tetrabromobisphenol A and derivatives.

    (Environmental health criteria ; 172)

    1.Bromine compounds   2.Environmental exposure
    3.Occupational exposure   4.Flame retardants  I.Series

    ISBN 92 4 157172 1                 (NLM Classification: QD 181.B7)
    ISSN 0250-863X

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    CONTENTS

    ENVIRONMENTAL HEALTH CRITERIA FOR TETRABROMOBISPHENOL A AND
    DERIVATIVES

    Preamble

    Introduction

    TETRABROMOBISPHENOL A

    1. Summary and evaluation; conclusions and recommendations

         1.1. Summary and evaluation
               1.1.1. Physical and chemical properties
               1.1.2. Production and use
               1.1.3. Environmental transport, distribution, and
                       transformation
               1.1.4. Environmental levels and human exposure
               1.1.5. Kinetics and metabolism in laboratory animals and
                       humans
               1.1.6. Effects on laboratory mammals and  in vitro test
                       systems
               1.1.7. Effects on humans
               1.1.8. Effects on other organisms in the laboratory and
                       field
         1.2. Conclusions
               1.2.1. General population
               1.2.2. Occupational exposure
               1.2.3. The environment
               1.2.4. Breakdown products
         1.3. Recommendations
               1.3.1. General
               1.3.2. Further studies

    2. Identity, physical and chemical properties, analytical methods

         2.1. Identity
               2.1.1. Technical product
         2.2. Physical and chemical properties
         2.3. Conversion factor for air concentrations
         2.4. Analytical methods

    3. Sources of human and environmental exposure

         3.1. Natural occurrence
         3.2. Anthropogenic sources
               3.2.1. Production levels and processes
               3.2.2. Uses

    4. Environmental transport, distribution, and transformation

         4.1. Transport and distribution between media
         4.2. Transformation
               4.2.1. Biotransformation
               4.2.2. Biodegradation
               4.2.3. Photodegradation
               4.2.4. Bioaccumulation
         4.3. Interaction with other physical, chemical, and biological
               factors
               4.3.1. Pyrolysis
               4.3.2. Pyrolysis of TBBPA-containing polymers
               4.3.3. Extrusion experiments with TBBPA-containing
                       polymers
               4.3.4. Reports on fires involving TBBPA
         4.4. Ultimate fate following use
               4.4.1. Disposal
               4.4.2. Recycling of TBBPA-containing polymers

    5. Environmental levels and human exposure

         5.1. Environmental levels
               5.1.1. Air
               5.1.2. Water
               5.1.3. Soil
               5.1.4. Fish and shellfish
         5.2. General population exposure
         5.3. Occupational exposure

    6. Kinetics and metabolism in laboratory animals and humans

         6.1. Absorption and elimination
               6.1.1. Mammals
               6.1.2. Fish and shell-fish
         6.2. Metabolism

    7. Effects on laboratory mammals and  in vitro test systems

         7.1. Single exposure
               7.1.1. Oral
               7.1.2. Dermal
               7.1.3. Inhalation
         7.2. Short-term exposures
               7.2.1. Oral (rat)
               7.2.2. Inhalation (rat)
               7.2.3. Dermal (rabbit)
         7.3. Long-term exposure
         7.4. Skin and eye irritation; sensitization
               7.4.1. Skin irritation
               7.4.2. Eye irritation

               7.4.3. Sensitization
               7.4.4. Chloracnegenic activity
         7.5. Reproductive toxicity, embryotoxicity, and teratogenicity
               7.5.1. Teratogenicity
         7.6. Mutagenicity and related end-points
         7.7. Carcinogenicity
         7.8. Other special studies

    8. Effects on humans

    9. Effects on other organisms in the laboratory and field

         9.1. Laboratory studies
               9.1.1. Microorganisms
                       9.1.1.1    Water
                       9.1.1.2    Soil
               9.1.2. Aquatic organisms
                       9.1.2.1    Invertebrates
                       9.1.2.2    Fish
               9.1.3. Sediment-dwelling organisms
         9.2. Field observations
         9.3. Miscellaneous

    TETRABROMOBISPHENOL A DERIVATIVES

    A.   TETRABROMOBISPHENOL A DIMETHYLETHER

         A.1   Summary and evaluation; conclusions and recommendations
         A.2   Identity, physical and chemical properties, and analytical
               methods
               A.2.1   Identity
         A.3   Sources of human and environmental exposure
         A.4   Environmental levels and human exposure
               A.4.1   Sediment
               A.4.2   Fish and shellfish

    B.   TETRABROMOBISPHENOL A DIBROMOPROPYLETHER

         B.1   Summary and evaluation; conclusions and recommendations
         B.2   Identity, physical and chemical properties, and analytical
               methods
               B.2.1   Identity
               B.2.2   Physical and chemical properties
         B.3   Sources of human and environmental exposure
               B.3.1   Uses
         B.4   Environmental transport, distribution, and transformation
         B.5   Effects on laboratory mammals and  in vitro test systems
               B.5.1   Single exposure
               B.5.2   Short-term exposures

               B.5.3   Mutagenicity and related end-points
                       B.5.3.1    Mutation
                       B.5.3.2    Unscheduled DNA synthesis assay
                       B.5.3.3     In vitro sister chromatid exchange
                                  in Chinese hamster ovary cells

    C.   TETRABROMOBISPHENOL A BIS(ALLYLETHER)

         C.1   Summary and evaluation; conclusions and recommendations
         C.2   Identity, physical and chemical properties, and analytical
               methods
               C.2.1   Identity
               C.2.2   Physical and chemical properties
               C.2.3   Analytical methods
         C.3   Sources of human and environmental exposure
               C.3.1   Uses
         C.4   Effects on laboratory mammals and  in vitro test systems
               C.4.1   Single exposure
               C.4.2   Skin and eye irritation; sensitization
               C.4.3   Mutagenicity and related end-points

    D.   TETRABROMOBISPHENOL A BIS(2-HYDROXYETHYL ETHER)

         D.1   Summary and evaluation; conclusions and recommendations
         D.2   Identity, physical and chemical properties, and analytical
               methods
               D.2.1   Identity
               D.2.2   Physical and chemical properties
         D.3   Sources of human and environmental exposure
         D.4   Environmental transport, distribution, and transformation
         D.5   Environmental levels and human exposure
               D.5.1   Environmental levels
                       D.5.1.1    Air
                       D.5.1.2    Water
                       D.5.1.3    Soil
         D.6   Effects on laboratory mammals and  in vitro test systems
               D.6.1   Single exposure
               D.6.2   Short-term exposures
               D.6.3   Skin and eye irritation; sensitization
               D.6.4   Mutagenicity and related end-points

    E.   TETRABROMOBISPHENOL A BROMINATED EPOXY OLIGOMER

         E.1   Summary and evaluation; conclusions and recommendations
         E.2   Identity, physical and chemical properties, and analytical
               methods
               E.2.1   Identity
               E.2.2   Physical and chemical properties
               E.2.3   Analytical methods

         E.3   Sources of human and environmental exposure
               E.3.1   Natural occurrence
               E.3.2   Anthropogenic sources
                       E.3.2.1    Production levels and processes
                       E.3.2.2    Uses
         E.4   Environmental transport, distribution, and transformation
               E.4.1   Pyrolysis of polymers containing brominated epoxy
                       oligomers

    F.   TETRABROMOBISPHENOL A CARBONATE OLIGOMERS

         F.1   Summary and evaluation; conclusions and recommendations
         F.2   Identity, physical and chemical properties, analytical
               methods
               F.2.1   Identity of BC-52
                       F.2.1.1    Physical and chemical properties
               F.2.2   Identity of BC-58
                       F.2.2.1    Physical and chemical properties
         F.3   Sources of human and environmental exposure
               F.3.1   Uses
         F.4   Environmental transport, distribution, and transformation
               F.4.1   Transport and distribution
               F.4.2   Transformation
                       F.4.2.1    Pyrolysis
                       F.4.2.2    Monitoring of PBDF/PBDD during extrusion
                                  blending and injection moulding
                       F.4.2.3    PBDD/PBDF levels in polymer samples
                                  using BC52-powder, BC52-batch, and the
                                  moulded test articles produced from
                                  these
         F.5   Environmental levels and human exposure
         F.6   Effects on laboratory mammals and  in vitro test systems
               F.6.1   Single exposure
               F.6.2   Skin and eye irritation; sensitization
               F.6.3   Mutagenicity and related end-points

    REFERENCES

    RESUME ET EVALUATION; CONCLUSIONS ET RECOMMANDATIONS

    RESUMEN Y EVALUACION; CONCLUSIONES Y RECOMENDACIONES
    

    NOTE TO READERS OF THE CRITERIA MONOGRAPHS

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         A detailed data profile and a legal file can be obtained from the
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         This publication was made possible by grant number 5 U01
    ES02617-15 from the National Institute of Environmental Health
    Sciences, National Institutes of Health, USA, and by financial support
    from the European Commission.

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    FIGURE 1

    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR
    TETRABROMOBISPHENOL A AND DERIVATIVES

     Members

    Dr D. Anderson, BIBRA Toxicology International, Carshalton, United
       Kingdom

    Dr R. Benson, Drinking Water Branch, US EPA, Denver, USA

    Dr B. Jansson, Institute of Applied Environmental Research, Stockholm
       University, Solna, Sweden

    Dr J. Kielhorn, Fraunhofer Institute for Toxicology and Aerosol
       Research, Hanover, Germany

    Dr R.D. Kimbrough, Institute for Evaluating Health Risks, Washington
       DC, USA  (Vice-chairman)

    Dr D. Osborn, Institute of Terrestrial Ecology, Monks Wood,
       Huntingdon, United Kingdom

    Dr Wai-On Phoon, Department of Occupational Health, University of
       Sydney, Sydney, Australia  (Chairman)

    Dr J. Sekizawa, National Institute of Health Sciences, Tokyo, Japan
        (Rapporteur)

    Dr E. Söderlund, National Institute of Public Health, Oslo, Norway

     Observers

    Dr M.L. Hardy, Albemarle Corporation, Baton Rouge, USA

    Dr D.L. McAllister, Quality, Environment, Health and Safety, and
       Research Support, Great Lakes Chemical Corporation, West
       Lafayette, USA

     Secretariat

    Dr K.W. Jager, International Programme on Chemical Safety, World
       Health Organization, Geneva, Switzerland  (Secretary)

    ENVIRONMENTAL HEALTH CRITERIA FOR TETRABROMOBISPHENOL A AND
    DERIVATIVES

         A WHO Task Group on Environmental Health Criteria for
    Tetrabromobisphenol A and Derivatives met at BIBRA Toxicology
    International, Carshalton, United Kingdom, from 6 to 11 June 1994.
    Dr K.W. Jager, IPCS, welcomed the participants on behalf of
    Dr M. Mercier, Director of the IPCS, and the three IPCS cooperating
    organizations (UNEP/ILO/WHO).  The Group reviewed and revised the
    draft and made an evaluation of the risks for human health and the
    environment from exposure to Tetrabromobisphenol A and derivatives.

         The first draft was prepared by Dr G.J. van Esch, the
    Netherlands, who also prepared the second draft, incorporating
    comments received following circulation of the first drafts to the
    IPCS Contact Points for Environmental Health Criteria monographs.

         Dr K.W. Jager of the IPCS Central Unit was responsible for the
    scientific content of the monograph and Mrs M.O. Head of Oxford for
    the technical editing.

         The fact that industry made available to the IPCS and the Task
    Group their proprietary toxicological information on their products
    under discussion is gratefully acknowledged.  This allowed the members
    of Task Group to make their evaluation on a more complete data base.

         The efforts of all who helped in the preparation and finalization
    of the monograph are gratefully acknowledged.

    INTRODUCTION

         Tetrabromobisphenol A (TBBPA) is an important flame retardant. 
    The demand for tetrabromobisphenol A and its derivatives accounts for
    over 60 000 tonnes per year.

         Whatever their use, flame retardants will ultimately end up in
    the environment, as such, or as break-down products.  In the case of
    tetrabromobiphenol A, the ultimate breakdown products and their levels
    may be different, depending on whether TBBPA has been used as a
    reactive or as an additive flame retardant.

         In order to make a proper assessment of the hazards of a
    substance for humans and the environment, it is essential that data
    are available not only on toxicity and ecotoxicity but also on:

    *    the ultimate fate of the substance under various use and disposal
         conditions, including incineration, and on its breakdown
         products; and

    *    the persistence and bioaccumulation/biomagnification of the
         substance and its breakdown products.

         The IPCS is preparing several EHC monographs on Flame Retardants,
    which will provide additional information relevant to TBBPA.

         One monograph, Flame retardants - General introduction (in
    preparation), will include a general introduction to the uses, the
    modes of action, and the potential risks of flame retardants, and also
    a list of the substances used as flame retardants with a general
    indication of the data available on them.

         Flame retardants in wide use are discussed in separate
    monographs, e.g., EHC 162: Polybrominated Diphenyl Ethers.

         Some flame retardants, considered hazardous for humans and the
    environment, have also been reviewed in separate monographs including
    EHC 152: Polybrominated Biphenyls, and EHC 173: Tris- and
    bis(2,3-dibromopropyl) Phosphate.

         Because of the possibility of the formation of halogenated
    dibenzodioxins and dibenzofurans under certain circumstances, such as
    pyrolysis, the following monographs have been developed: EHC 88:
    Polychlorinated dibenzo- para-dioxins and dibenzofurans and
    Polybrominated dibenzodioxins and dibenzofurans (in preparation).

         The reader should consult these monographs for further
    information.

    TETRABROMOBISPHENOL A

    1.  SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS ON
        TETRABROMOBISPHENOL A (TBBPA)

    1.1  Summary and evaluation

    1.1.1  Physical and chemical properties

         TBBPA is a white (colourless), crystalline powder, containing 59%
    bromine.  The melting point is approximately 180°C and the boiling
    point, 316°C.  Vapour pressure is much less than 1 mmHg at 20°C. TBBPA
    has a low solubility in water, but is very soluble in methanol and
    acetone.  The  n-octanol/water partition coefficient (log Pow) is
    4.5.

    1.1.2  Production and use

         Commercial TBBPA is the brominated flame retardant produced in
    the largest amounts globally.  The demand for TBBPA and its
    derivatives accounts for over 60 000 tonnes per year.  TBBPA is used
    as a reactive (primary use) or additive flame retardant in polymers,
    such as ABS, epoxy and polycarbonate resins, high impact polystyrene,
    phenolic resins, adhesives, and others.

    1.1.3  Environmental transport, distribution, and transformation

         Because of its partition coefficient and low water solubility,
    TBBPA in the environment is expected to sorb to a large extent onto
    sediment and organic matter in the soil.

         Accumulation studies on aquatic invertebrates and vertebrates
    indicate bioconcentration factors ranging from 20 to 3200.  The
    half-life in fish is less than 1 day, and that in oysters, less than
    5 days.  During depuration, most of the accumulated TBBPA (and
    metabolites) will be eliminated within 3-7 days.

         Biodegradation studies showed that TBBPA is partly degraded under
    both aerobic and anaerobic conditions, in soil, and in river sediment
    and water.  Depending on soil type, temperature, humidity, and the
    composition of the soil, approximately 40-90% of TBBPA remained in the
    soils after 56-64 days.  Under sewage treatment conditions, no
    biodegradation was detected, as measured as BOD, in 2 weeks.

         Laboratory pyrolysis studies showed that polymers with TBBPA,
    with and without the presence of Sb2O3, at different temperatures,
    in the presence of oxygen, etc., may form polybrominated dibenzofurans
    (PBDF) and, to a lesser extent, polybrominated dibenzodioxins (PBDD).
    Mainly lower brominated PBDF and PBDD are formed.  When polymers
    formulated with TBBPA, exposed to simulating thermal processing

    conditions, were analysed, 2,3,7,8-PBDD/PBDF were not detected.  Only
    mono- or dibromo-substituted PBDF were detected at up to 100 µg/kg
    levels in the resin.  Investigation of the workplace atmosphere showed
    no 2,3,7,8-substituted PBDD/PBDF (detection limit = 0.1 ng/m3).

         In recycled TBBPA-containing polymers, less than 5 µg total
    PBDF/PBDD per kg were detected and 2,3,7,8-substituted congeners were
    only found at levels of less than 0.2 µg/kg.

         In a warehouse fire, in which a great quantity of polybutylene
    terephthalate (PBT) containing TBBPA was burnt, only low levels of
    2,3,7,8-substituted tetra-, penta-, and hexa-BDF/BDD (less than
    5 µg/kg) were detected in burnt PBT and ash/slag samples.

    1.1.4  Environmental levels and human exposure

         TBBPA was detected in some sediments in Japan and Sweden and in
    fish (2 samples near an industrialized area out of 229 samples) in
    µg/kg levels in Japan.  The dimethoxy derivative of TBBPA could be
    identified in mussels and sediment.  TBBPA was not generally detected
    in water.

    1.1.5  Kinetics and metabolism in laboratory animals and humans

         In rats, TBBPA is poorly absorbed from the gastrointestinal
    tract.  Once absorbed, it and/or its metabolites appear to be
    distributed throughout most organs of the body.  In the rat, the
    maximum half-life in any tissue was less than 2 1/2 days.

    1.1.6  Effects on laboratory mammals and  in vitro test systems

         The acute oral toxicity of TBBPA for laboratory animals is low. 
    The oral LD50 for the rat was > 5 g/kg body weight and the oral
    LD50 for the mouse was 10 g/kg body weight.  The dermal LD50 for
    the rabbit was > 2 g/kg body weight.  The inhalation LC50s for the
    mouse, rat, and guinea-pig were > 0.5 mg/litre.  A single dermal
    application of TBBPA on the skin of rabbits and guinea-pigs did not
    induce local or systemic effects at concentrations of up to 3.16 g/kg
    body weight.  TBBPA was not irritating to rabbit skin or eyes.  No
    sensitization reaction was observed in a few studies on guinea-pigs. 
    TBBPA was also tested for chloracnegenic activity in rabbit ears.  No
    such reaction was observed.  A 3-week dermal toxicity study, in which
    the clipped and abraded skin of rabbits was exposed to up to 2500 mg
    TBBPA/kg body weight, showed only slight skin erythema.  No other
    compound-related changes were observed.

         Rats were exposed to up to 18 mg micronized TBBPA/litre
    (18 000 mg/m3) for 4 h/day, 5 days/week for 2 weeks.  No effects on
    body weight, histopathology, haematology, serum chemistry, or
    urinalysis were observed. 

         Oral doses to rats of up to 1000 mg TBBPA/kg diet for 28 days did
    not produce any adverse effects.  The total bromine contents of the
    liver did not differ between the control and high-dose (1000 mg/kg)
    groups. 

         In an oral, 90-day toxicity study on rats, dose levels of up to
    100 mg TBBPA/kg body weight did not induce any adverse effects on body
    weight, haematology, clinical chemistry, urinalysis, organ weights, or
    gross and microscopic examinations.

         In an oral, 90-day study on mice, a dose of 4900 mg/kg diet
    (approximately 700 mg/kg body weight per day) did not cause any
    adverse effects; a dose of 15 600 mg/kg diet (approximately 2200 mg/kg
    body weight per day) caused decreased body weight, increased spleen
    weight, and reduced concentration of red blood cells, serum proteins,
    and serum triglyceride.

         Two teratogenicity studies were carried out on rats; one in which
    dose levels of up to 10 g/kg body weight were administered by gavage
    from gestation day 6 to day 15 and a second in which dose levels of up
    to 2.5 g/kg body weight were administered from day 0 to day 19 of
    gestation.  In the first study, 3/5 animals receiving 10 g/kg died,
    but no signs of toxicity were noticed in animals receiving 3 g/kg.  No
    teratogenic effects were observed.  No abnormalities were found in the
    second study.

         TBBPA was not mutagenic in various studies with  Salmonella
     typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100 with
    metabolic activation by an S9 mix of Aroclor-induced rats and Syrian
    hamsters.  The concentrations tested were up to 10 000 µg/plate.  The
    results of two tests with  Saccharomyces cerevisiae, with and without
    microsomal enzyme preparation from Aroclor-induced rats, were also
    negative.

         No carcinogenicity or long-term toxicity studies were reported.

    1.1.7  Effects on humans

         TBBPA did not produce any skin irritation or sensitization in 54
    human volunteers.

         No epidemiological studies or other data on the effects on humans
    are available.

    1.1.8  Effects on other organisms in the laboratory and field

         TBBPA was not very toxic for marine algae.  In 28 short-term
    studies, the EC50s were in the range of 0.1-1.0 mg/litre, while
    fresh water algae did not show growth inhibition, even at
    9.6 mg/litre.

         An acute 48-h LC50 for  Daphnia magna was reported to be
    0.96 mg/litre; at 0.32 mg/litre, 5% of the organisms died.  In a
    21-day study, however, the EC50 for survival and growth of  Daphnia
     magna was > 0.98 mg/litre. Based on the effects of TBBPA on daphnid
    reproduction in this 21-day study, a Maximum Acceptable Toxicant
    Concentration (MATC) was between 0.30 and 0.98 mg/litre.  Mysid shrimp
    (age < 1, 5, and 10 days old) showed 96-h LC50 values of 0.86, 1.1,
    and 1.2 mg/litre, respectively.

         The 96-h acute EC50 (reduction of shell deposition) in Eastern
    oysters was calculated to be 0.098 mg/litre with a no-observed-effect
    concentration (NOEC) of 0.0062 mg/litre.

         The 96-h LC50s of TBBPA for bluegill sunfish, rainbow trout,
    and fathead minnow were 0.51, 0.40, and 0.54 mg/litre, respectively. 
    The no-effect concentrations for these three fish species were 0.10,
    0.18, and 0.26 mg/litre.  Fathead minnow (embryos and larvae) were
    exposed for 35 days to TBBPA and showed a MATC of between 0.16 and
    0.31 mg/litre, based on adverse effects on embryo and larvae survival.

         The 14-day, no-effect levels for the sediment invertebrate midge
    Chironomous tentans were 0.039, 0.045, and 0.046 mg TBBPA/litre water
    in low, medium, and high organic carbon sediments, respectively.

         Most of the studies on aquatic systems have been performed at pHs
    around the pKa2.  The behaviour of TBBPA in acidic waters may be
    different.

    1.2  Conclusions

    1.2.1  General population

         TBBPA is widely used and incorporated in polymers as a reactive
    or additive flame retardant.  Contact of the general population is
    with products made from these polymers and  would not result in
    significant uptake of TBBPA.  Furthermore, the acute and repeated dose
    toxicity of TBBPA is very low. TBBPA is poorly absorbed from the
    gastrointestinal tract.  The risk for the general population from
    TBBPA exposure is, therefore, considered to be insignificant.

    1.2.2  Occupational exposure

         Occupational exposure to TBBPA is primarily as particulates
    during packaging or mixing operations.  The control of dust through
    the use of local ventilation and other engineering methods will reduce
    the risk to workers.  If dust cannot be adequately controlled,
    respiratory protection should be used.

    1.2.3  The environment

         Where detected in the environment, TBBPA is mainly found in soil
    and sediment samples.  A relatively high bioconcentration factor seems
    to be balanced by rapid excretion and the compound has not normally
    been found in environmental biological samples.

         The phenolic groups of TBBPA may be methylated in the environment
    and the resulting Me2-TBBPA is more lipophilic.  This compound has
    also been found in sediment, fish, and shellfish.

    1.2.4  Breakdown products

         PBDD and PBDF have been found as trace impurities in TBBPA;
    however, the presence of 2,3,7,8-congeners has not been demonstrated. 
    Under laboratory pyrolysis conditions, PBDF/PBDD are formed from
    TBBPA.

         A limited number of studies have shown that only trace quantities
    of PBDF/PBDD may be produced during the processing and recycling of
    polymers containing TBBPA as an additive flame retardant.  Proper
    ventilation and other engineering controls can prevent worker
    exposure.

    1.3  Recommendations

    1.3.1  General

    *    Workers in the manufacture of TBBPA and products containing the
         compound should be protected from exposure by means of
         engineering controls, monitoring of occupational exposure, and
         appropriate industrial hygiene measures.

    *    Environmental exposure should be minimized through the
         appropriate treatment of effluents and emissions in industries
         using the compound or products.

    *    Disposal of industrial wastes and consumer products should be
         controlled to minimize environmental contamination with this
         material and its breakdown products.

    *    If TBBPA-treated material is incinerated, it has to be done in
         properly constituted incinerators running at consistently optimal
         conditions.

    1.3.2  Further studies

    *    Monitoring of environmental samples for TBBPA, Me2-TBBPA, and
         PBDF/PBDD should be continued, and if these compounds are found,
         human monitoring should also be carried out.

    *    Monitoring should be conducted to measure occupational exposures
         to respirable particles of TBBPA; if indicated by workplace
         monitoring, a short-term inhalation study on rats should be
         conducted.

    *    Studies on PBDF/PBDD formation from TBBPA-treated material during
         incineration, accidental fires, and under conditions simulating
         fire, should be conducted.

    *    Long-term studies of the fate of polymers containing TBBPA (both
         added and reacted into the polymer), especially in land fills,
         should be conducted.

    *    Environmental conversion of TBBPA to its dimethyl derivative,
         especially in sediments, should be studied.

    *    Studies on the recyclability of TBBPA-containing polymers should
         be continued, paying attention to break-down products.

    *    Since there are no data, an additional  in vitro test with TBBPA
         for cytogenetic damage is required.  If this test is positive,
         additional  in vivo studies will be necessary.  If the
         cytogenetic testing  in vivo shows positive results, additional
         short- or long- term testing is required.

    *    Since there are no data, a test for reproductive toxicity in rats
         is required.

    2.  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

    2.1  Identity

    Chemical formula         C15H12Br4O2

    Chemical structure       CHEMICAL STRUCTURE 1
















    Relative molecular
      mass                   543.92

    Chemical name            phenol, 4,4'-(1-methylethylidene)
                              bis[2,6-dibromo-]

    Common abbreviation      TBBPA

    CAS registry
     number                  79-94-7

    EINECS number            2012369

    Synonyms                 4,4'-isopropylidene-bis(2,6-dibromophenol);
                             2,2-bis(3,5-dibromo-4-hydroxyphenyl)
                             propane; phenol, 4,4'-isopropylidenebis
                             (dibromo-); 3,3',5,5'-tetrabromobisphenol
                             A; tetrabromodian: tetrabromodihydroxy
                             diphenylpropane.

    2.1.1  Technical product

    Trade names              Great Lakes BA-59P; Saytex RB-100;
                             Saytex RB-100 ABS; FR-1524; Bromdian;
                             FG 2000; Fire Guard 2000; Firemaster BP 4A;
                             Tetrabrom

    2.2  Physical and chemical properties

         Tetrabromobisphenol A (TBBPA) is a white (colourless),
    crystalline or powdered solid with a slight characteristic odour,
    containing 58.7% bromine.

         The purity of commercial TBBPA is 98.5% containing 0.1% water, a
    maximum of 60 mg hydrolysable bromine/kg, and a maximum of 100 mg
    ionic bromide/kg (Ethyl Corporation, 1992b).

         In experiments to determine levels of breakdown products in the
    technical compounds, Thoma et al. (1986a) found hexa-, penta-, and
    octa-brominated dibenzofurans (12, 31, 19 µg/kg, respectively) in a
    sample of technical grade TBBPA.  Thies et al. (1990), measuring mono-
    to hexa-BDF/BDD in a commercial sample of TBBPA, reported a total of
    less than 20 µg/kg; neither 2,3,7,8-TeBDD nor 2,3,7,8-TeBDF was
    detectable (detection limit, 0.5 µg/kg).

         In an ultratrace analysis specific for 15 different PBDF/PBDD
    having bromine in the 2,3,7,8-positions (Tondeur et al., 1990), none
    of these specific congeners were found in TBBPA (limit of
    determination for the 15 different 2,3,7,8-substituted PBDF/PBDD
    ranged from 0.1 up to 1000 µg/kg) (Ranken, 1993; Remmers et al.,
    1993).

         Physical and chemical properties of commercial products are
    summarized in Table 1.

    2.3  Conversion factor for air concentrations

         1 ppm = 0.02 mg/litre under standard conditions (Bayer, 1990).

    2.4  Analytical methods

         TBBPA can be converted to the diethyl derivative by ethylation,
    and the resulting product can be determined by gas chromatographic
    (GC) and gas chromatographic/mass spectrometric (GC/MS) analysis
    (Gustafsson & Wallen, 1988).

         Seawater samples were acidified with HCl, extracted with
    petroleum ether, concentrated, and taken up in hexane.  Quantification
    was performed with on-column capillary gas chromatography using an
    electron-capture detector.  The response of the detector was linear
    from 0.50 to 5.0 ng.  The limit of determination was 1.0 µg/litre. 
    Recovery of fortified TBBPA at 535 µg/litre was 99%, and, at
    84 µg/litre, 93 ± 11.5% (Goodman et al., 1988).

         TBBPA determination in freshwater was carried out by HPLC
    analysis.  A C18 column was used and the mobile phase was a
    80/20 acetonitrile/HPLC grade water mixture using a UV detector
    (wavelength 230 nm). The average recovery of TBBPA from water was
    96.1%.  The theoretical, minimum detectable concentration was
    < 2.22 µg/ml active ingredient (Surprenant, 1988, 1989a).

         Watanabe et al. (1983a) described an analytical method to
    determine TBBPA in sediment. The TBBPA in the extract was converted to
    a diethylether derivative by ethylation.  This derivative was
    identified and determined by gas chromatography (ECD-63Ni detector)
    and gas chromatography/mass spectrometry.  This extraction, clean-up,
    and determination method was also used to determine TBBPA in mussel
    tissue.  A method was also given to determine methoxy-TBBPA in mussel
    tissue.

    3.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    3.1  Natural occurrence

         TBBPA is not reported to occur naturally.

    3.2  Anthropogenic sources

    3.2.1  Production levels and processes

         TBBPA is the largest selling brominated flame retardant
    accounting for an annual market of 41 000 tonnes (Japan -
    15 000 tonnes, USA - 16 000 tonnes, and Europe 10 000 tonnes) (OECD,

    Table 1.  Physical and chemical properties of commercial products
                                                                        

    Melting point            181-182°Ca,b

    Boiling point            316°C (approximately)b

    Specific gravity         2.18a

    Flash point              178°Cb

    Vapour pressure          < 1 mmHg at 20°Cb

    Solubility in water      0.72 mg/litre at 15°C* (< 0.1 wt% at 25°C)b
                             4.16 mg/litre at 25°C*b
                             1.77 mg/litre at 35°C*b
                             in methanol, 920 g/litre (47.2 wt% at 25°C)a
                             in acetone, 2400 g/litre (69.6 wt% at 25°C)a
                             in toluene 6.4 wt% at 25°Ca
                             in styrene < 1.0 wt% at 25°Ca

     n-Octanol/water
     partition coefficient
     (log Pow)               4.5-5.3b

    pKa1 and pKa2            7.5 and 8.5, respectivelyb
                                                                        

    a  From: Ethyl Corporation (1992a,b);
       Great Lakes Chemical Corporation (1986).
    b  From: Bayer (1990).
    *  The water solubility was determined by radioassay,
       using (phenyl-UL-14C) labelled TBBPA.


    1993).  About 10 000 tonnes/year of TBBPA derivatives are produced
    (Satoh & Sugie, 1993).  In the USA, 5000-6350 tonnes were reported to
    have been used in 1982.

         In 1987, Sweden imported more than 100 tonnes, and the
    Netherlands consumed 200 tonnes in 1988.  The USA imported 660 tonnes
    in 1983 and produced 39 000 tonnes in 1983/1984 (Gustafsson & Wallen,
    1988). The annual consumption of TBBPA in Japan was 14 400 tonnes in
    1987, 18 000 tonnes in 1988, 23 000 tonnes in 1990, 24 500 tonnes in
    1991, 23 000 tonnes in 1992, and 22 000 tonnes in 1993, mainly for use
    in flame retarding polystyrene (ABS, HIPS) and PC, and, partly for use
    in the manufacturing of derivatives (Tatsukawa & Watanabe, 1990;
    Watanabe & Tatsukawa, 1990; The Chemical Daily, 1990-1994).

         Tetrabromobisphenol A (TBBPA) is produced by the bromination of
    bisphenol A (BPA) in the presence of a solvent.  The bromination
    reaction is generally conducted in solvents, such as a halocarbon
    alone, or with water or 50% hydrobromic acid, or aqueous alkyl
    monoethers.  Aqueous acetic acid is also a satisfactory medium and
    acetic acid with added sodium acetate is reported to improve product
    colour (Ullmann, 1985).  If methanol is used as a solvent, the
    fumigant methyl bromide is produced as a co-product.  The BPA
    dissolved in methanol is reacted with bromine to yield TBBPA and
    hydrobromic acid.  The methanol reacts further with the hydrobromic
    acid to yield methyl bromide.  This process is used by Ethyl
    Corporation and Great Lakes Chemical Corporation (Ethyl Corporation,
    personal communication, 1990).  Dead Sea Bromine, who produce TBBPA at
    plants in Israel and the Netherlands, do not use this method but
    another process (Dead Sea Bromine, personal communication, 1994).

         Following the synthesis, the TBBPA is precipitated from the
    methanol, separated by filtration, and washed to remove impurities. 
    The solid product is dried and then packaged in bags, drums, or bulk
    containers.

         The process is largely conducted in enclosed equipment, therefore
    limiting the possibility of worker exposure.  However, some exposure
    to dust may occur during the packaging process.

    3.2.2  Uses

         The primary use of TBBPA is as a reactive intermediate in the
    manufacture of flame-retarded epoxy and polycarbonate resins,
    accounting for approximately 90% of TBBPA used.  The identity of TBBPA
    is lost in the process of polymerization (McAllister, personal
    communication, 1994).  Polymerization is typically conducted in
    totally enclosed equipment, minimizing the possibility of worker
    exposure.  A principal use of TBBPA epoxy resins is in printed circuit
    boards where the bromine content may be 20% by weight (34% TBBPA).

         As an additive flame retardant, TBBPA, in the form of a dry
    powder, is mixed with various polymers.  Dusting may occur during
    mixing.  It does not react chemically with the other compounds, and,
    therefore, may leach out of the polymer matrix.  Additive use accounts
    for approximately 10% of TBBPA used (McAllister, personal
    communication, 1994).  For example, TBBPA may be used as an additive
    flame retardant in acrylonitrile-butadiene-styrene (ABS) resins and in
    high impact polystyrene.  TBBPA can be used as an additive flame
    retardant in ABS thermoplastics, in polystyrene, and in phenolic
    resins.  Recommended starting levels of TBBPA in ABS (medium to high
    impact) are 17.6-22.0% and 14% in high impact polystyrene.  ABS resins
    are used in automotive parts, pipes and fittings, refrigerators, other
    appliances, business machines, and telephones.  Polystyrene is used in
    packaging, consumer products, disposables, electrical and electronic
    equipment, furniture, and in building and construction materials

    (Quast et al., 1975; Personal communication on opportunities for
    cooperation on acrolein and tetrabromobisphenol A from Gustafsson K &
    Wallen M of National Chemicals Inspectorate, Scientific Documentation
    and Research, Solna, Sweden, in 1988).

         When used as a flame retardant in encapsulated integrated circuit
    devices, TBBPA may be combined with an additional flame retardant,
    such as antimony trioxide.  TBBPA can be used as a reactive flame
    retardant in polycarbonate and unsaturated polyester resins. 
    Polycarbonates are used in communication and electronics equipment
    (i.e., business machines), appliances, transportation devices, sports
    and recreation equipment, lighting fixtures and signs.

         Unsaturated polyesters are used for making simulated marble floor
    tiles, bowling balls, glass-reinforced panels, furniture parts, sewer-
    pipes coupling compound, automotive patching compounds, buttons, and
    for encapsulating electrical devices (Gustafsson & Wallen, 1988).

         TBBPA may also be used as an intermediate for the production of
    other flame retardants, such as the bis(2-hydroxyethyl ether) of
    TBBPA, as a flame retardant for paper and textiles, in adhesives and
    coatings, and for imparting corrosion resistance to unsaturated
    polyesters used in chemical processing equipment (Gustafsson & Wallen,
    1988).

         The total use of TBBPA derivatives is only about 25% as large as
    the use of TBBPA itself (McAllister, personal communication, 1994).

    4.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

    4.1  Transport and distribution between media

         Because of its partition coefficient and low water solubility,
    TBBPA in the environment is expected to sorb onto sediment and organic
    matter in soil.

    4.2  Transformation

    4.2.1  Biotransformation

         The dimethyl ether derivative of TBBPA, thought to be a
    metabolite from microbial methylation, was found in river sediment
    collected in Osaka, Japan.  None was found in marine sediment
    collected in Osaka Bay, Japan. The dimethylated-TBBPA derivative was
    detected at about one-hundredth of the TBBPA levels concurrently
    measured in river sediment (Watanabe et al., 1983b).

         Sediment samples taken upstream and downstream from a factory in
    Sweden were analysed for TBBPA and dimethylatedTBBPA.  Up and
    downstream from the factory, the TBBPA levels were 50 and 430 ng/g
    ignition loss and those for methylated-TBBPA were 36 and 2400 ng/g
    ignition loss (Sellström, 1990).

    4.2.2  Biodegradation

         The biodegradability of 14C-TBBPA was tested under aerobic
    conditions in three soil types, i.e., Massachusetts sandy loam, a
    California loam, and Arkansas silty loam.  The three soil types
    contained: sand (83%) silt (13%) clay (4%), sand (16%) silt (58%) clay
    (26%), and sand (43%) silt (24%) clay (33%), respectively.  Thin layer
    chromatography (TLC) showed biodegradation of TBBPA in all soil types. 
    Only 6% or less of the applied radioactive TBBPA was recovered in the
    volatile traps, indicating only partial degradation.  Results of the
    TLC analysis indicated variable degradation rates of TBBPA.  After 64
    days, the amount of TBBPA remaining in the soils ranged from 82 to
    36%, with the highest levels in the sandy loam soil and the lowest in
    the silty loam soil (Fackler, 1989a).

         The biodegradability of TBBPA was tested under anaerobic
    conditions in three soil types: Massachusetts sandy loam (MSL),
    Arkansas silty loam (ASL), and California clay loam (CCL).  For the
    composition of these soils see the paragraph above.  TLC showed
    biodegradation of TBBPA in all soil types.  The temperature during the
    study was 19-25°C (mean 21.4°C).  Less than 0.5% of the applied
    radioactive TBBPA was recovered in the volatile traps, indicating only
    partial degradation.  The recovered radioactivity in the traps was
    almost exclusively CO2.  Results of the TLC analysis indicated
    variable degradation rates of TBBPA.  After 64 days, the amounts of
    TBBPA remaining in the soils were MSL: 43.7-57.4%, ASL: 53.4-65%, and
    CCL: 89.5-90.6%.  Radioactivity recovered from the water ranged from
    0.5 to 2.5% (Fackler, 1989d).

         In another study, the biodegradability of 14C-TBBPA was tested
    under aerobic conditions in a sediment/water microbial test system
    using natural river sediment and water.  The test conditions were
    pH 5.5, field moisture capacity 15.9%, temperature 24-26°C and the
    composition of the soil (6.8% carbon) was 92% sand, 6% silt, and 2%
    clay.  Oxygen was bubbled through the system for 5 min/day to maintain
    aerobic conditions.  The sampling intervals were scheduled on days 0,
    4, 7, 10, 14, 21, 28, 42, and 56.  Results from a 56-day aerobic test
    showed biodegradation of TBBPA in all tested concentrations, e.g.,
    0.01, 0.1, and 1 mg/litre.  Half-lives calculated for TBBPA in the
    sediment/water microbial test systems ranged between 48 (10 µg/litre)
    and 84 days (1000 µg/litre), with apparent correlations between half-
    life and TBBPA concentration, and half-life and microbial population. 
    The half-life in sterile soil could be extrapolated to be 1300 days,
    clearly indicating that the degradation observed in the active test

    systems was due to microbial degradation rather than physical
    processes.  Less than 8% of the applied radioactive carbon from TBBPA
    was recovered in the volatile (CO2) traps indicating only partial
    degradation.  Filtered water contained less than 5% of the applied
    radioactivity.  The amount of radioactivity observed to be remaining
    in the sediment at test termination, 44.7, 64.2, and 60.8% in the
    0.01, 0.1 and 1 mg radioactive TBBPA/litre treatments, respectively,
    was comparable to the amounts reported in the aerobic degradation
    study in soil (Fackler, 1989e).

         A biodegradation study on TBBPA (100 mg/litre) using sludge
    (30 mg/litre) for 2 weeks under sewage treatment condition showed no
    degradation by means of BOD (Chemical Inspection & Testing Institute,
    1992).

    4.2.3  Photodegradation

         The calculated half-life of decomposition of TBBPA in water by
    UVR was 10.2 days in spring, 6.6 in summer, 25.9 in autumn, and 80.7
    days in winter.  Cloud cover lengthened the calculated half-life by a
    factor of 2.  The water depth influenced the direct photodegradation
    more as the UV-absorption of the given body of water increased (Bayer,
    1990).

         In photodegradation experiments, TBBPA absorbed onto silica gel
    was exposed to UVR (254 nm).  Eight metabolites were detected.  The
    half-life value for TBBPA obtained in this test was 0.12 days (Bayer,
    1990).  It is difficult to derive environmental conclusions from the
    results of these experiments.

    4.2.4  Bioaccumulation

         TBBPA was labelled with 14C in the aromatic ring.  Blue gill
    sunfish  (Lepomis macrochirus) (0.5-2.0 g) were exposed in a flow-
    through system for a period of 28 days to 0.0098 ± 0.0014 mg per
    litre.  This was followed by a 14-day withdrawal period and
    bioaccumulation in edible tissue was determined.  The average tissue
    concentrations of 14C were found to be 0.196 mg/kg edible tissue and
    1.69 mg/kg non-edible tissue.  These values translated to
    bioconcentration factors (BCF) of 20 in edible tissue and 170 in
    visceral tissues.  Plateau levels were reached within 3-7 days.  In
    the fish, the whole body half-life was < 24 h.  The radiocarbon
    dissipation to less than 0.01 mg/kg in the fish tissue occurred within
    3-7 days of the beginning of the withdrawal phase (Nye, 1978).

         TBBPA bioconcentration was determined in a 14-day toxicity study
    on  Chironomous tentans (section 9.1.3). The bioconcentration factors
    calculated as the ratio of body concentration and interstitial water
    concentration ranged from 240 to 510 in high organic carbon sediments,
    490 to 1100 in medium organic carbon sediments, and 650 to 3200 in low

    organic carbon sediments.  Bioavailability of TBBPA increased with
    decreasing total organic carbon concentrations in the sediments
    (Breteler, 1989).

         Fathead minnows  (Pimephalus promelas) (20 fish) were
    continuously exposed to a mean measured concentration of 4.7 µg/litre,
    in a flow-through system, throughout the 24-day exposure period.  The
    mean length and weight of the fish were 39 ± 4 mm and 0.57 ± 0.2 g,
    respectively.  The water quality was: hardness and alkalinity 28 and
    20-26 mg/litre as CaCO3, respectively, pH 7.0-7.6, dissolved oxygen
    86-96% of saturation, and the temperature 19-21°C.  Throughout the
    6-day depuration period, concentrations of 14C remained below the
    limit of radiometric detection in water (0.29 µg/litre).  The
    concentration of 14C-residue in the tissue of fish reached a
    steady-state level on the fourth day of exposure.  The mean steady-state
    tissue concentration was 5.8 mg/kg, which established a bioconcentration
    factor (BCF) of 1200.  Following 6 days of depuration, 98% of the
    accumulated 14C residues were eliminated from the tissues of exposed
    fish.  The whole-body half-life was less than 1 day (Fackler, 1989c).

         Eastern oysters  (Crassostrea virginica) were continuously
    exposed to a mean, measured concentration of 1.0 µg/litre seawater for
    a 20-day exposure period.  The valve height of the oysters ranged from
    30 to 49 mm and they were determined to be immature by examination of
    the gonads.  Seawater salinity was 32-34%, pH 7.2-8.1, mean dissolved
    oxygen 7.4-7.5 mg/litre, and temperature 19°C.  Throughout the 14-day
    depuration period, concentrations of 14C remained below the limit of
    radiometric detection in water (0.34 µg/litre).  The concentration of
    14C residues reached a steady state level on the fifth day of
    exposure.  The bioconcentration factor (BCF) was 780.  The half-life
    of the 14C residues in the oysters was between 3 and 5 days
    (Fackler, 1989b).

         A bioaccumulation study on TBBPA (80 µg/litre, 8 µg/litre) using
    carp for 8 weeks showed 30-341 and 52-485 times bioaccumulation,
    respectively (Chemical Inspection & Testing Institute, 1992).

         Regression equations were used to estimate the bioconcentration
    factor in fish using log Pow.  Using the value 4.48 of log Pow, a
    log BCF of 3.2 is obtained.  Since a substantial fraction of TBBPA is
    expected to be ionized and more polar at environmental pH values, and
    this fraction is less readily taken up by lipid membranes of the gill
    (depending on the counteracting influence of the bulky, non-polar
    bromine substituents, which may "mask" the ionized hydroxyl group),
    the amount of TBBPA in a form readily concentrated may be diminished. 
    This probably accounts for the lower BCF values determined
    experimentally (Gustafsson & Wallen, 1988).

         TBBPA has pKa values of 7.5 and 8.5.  The aquatic toxicity tests
    were conducted at pHs ranging from 6.7 to 8.2. Interpretation of data
    for studies where the pH is close to the pKa may be difficult, because
    toxicity, bioaccumulation, depuration rates, and sediment binding will
    all be affected by the degree of dissociation exhibited.  In addition,
    the behaviour of TBBPA in acidic waters may be different from that in
    the test situation.

    4.3  Interaction with other physical, chemical, and biological factors

    4.3.1  Pyrolysis

         Purified TBBPA was pyrolysed in open quartz tubes at 700, 800, or
    900°C for 10 min.  The residues were analysed for PBDD and PBDF.  The
    pyrolysis of TBBPA gave mainly mono-, di-, tri-, and tetra-PBDD and -
    PBDF, but no highly brominated dibenzodioxins or dibenzofurans were
    found.  The PBDD and PBDF formation was 0.02, 0.16, and 0.10%,
    respectively at 700, 800, and 900°C.  At 900°C, the substance was
    partly decomposed.  At 800°C, the TeBDD and TeBDF isomers were
    produced at a concentration of 27 and 21 mg/kg of TBBPA, respectively
    (Thoma et al., 1986b).

         Thies et al. (1990) pyrolysed pure TBBPA at 600°C (10 or 20 min)
    producing primarily mono-tetra-BDF and BDD at individual
    concentrations of up to 130 000 µg/kg.  2,3,7,8-substituted congeners
    were produced at maximum concentrations of 10-50 µg/kg.

    4.3.2  Pyrolysis of TBBPA-containing polymers

         Epoxide resin with TBBPA, with 4-8% Sb2O3 or without
    Sb2O3, was tested for the formation of PBDD and PBDF by pyrolysis
    in a quartz tube at 400-800°C, under aerobic conditions.  Under these
    conditions, no PBDF or PBDD was found (limits of determination, 20 and
    10 mg/kg, respectively) (Clausen et al., 1987).

         The formation of 2,3,7,8-TeBBD and 2,3,7,8-TeBDF from epoxide
    resin with TBBPA was studied in pyrolysis experiments at 400, 600, and
    800°C.  The following samples were studied; epoxide resin with 6%
    TBBPA in combination with 5% Sb2O3 and copper oxide (CuO); epoxide
    resin with 6% TBBPA and copper oxide and epoxide resin with 6% TBBPA
    and copper.  2,3,7,8-TeBDD was not detected at 400°C, but, at 600 and
    800°C, in all three samples 1,3,6,8- and/or 1,3,7,9-tetrabromo-
    dibenzodioxin were found in concentrations of between 2.0 and
    6.0 mg/kg.  No 2,3,7,8-TeBDD or 2,3,7,8-TeBDF was found (limit of
    determination 0.01 mg/kg) (Lahaniatis et al., 1991).

         Dumler et al. (1989) pyrolysed polymers (in granular form) mixed
    with TBBPA.  The polymer mixtures were: Epoxide laminate/TBBPA;
    Epoxide laminate/TBBPA/copper laminate; PBT/TBBPA and Polycarbonate/

    TBBPA.  Three different ovens were used; the DIN-oven, the BIS-oven,
    and the VCI-oven.  The temperatures were 600 and 800°C.  Both the
    pyrolysis gases and the solid residues were analysed for PBDF and
    PBDD.  PBDF was found in almost all samples.  Polymers containing
    TBBPA generated small quantities of PBDF on pyrolysis, with yields
    ranging up to a few mg/kg.  Mono- to tri-brominated congeners were
    identified.

         The formation of PBDD and PBDF was studied during the pyrolysis
    of acrylonitrile/butadiene/styrene (ABS) with TBBPA at different
    temperatures and carrier gas compositions; mono- to
    pentabromodibenzofurans were formed at a µg/kg level.  The optimum
    temperature of formation of PBDD and PBDF was 600°C.  The thermal
    degradation processes of the polymer were investigated in a
    thermogravimetric analysis.  TBBPA did not exert any influence on the
    elementary chemical degradation processes of ABS.  The flame retardant
    activity of TBBPA consists of the emission of brominated radicals and
    reduced flammability.  The mechanism of formation of PBDD and PBDF
    from TBBPA, was found to be only a gas phase mechanism (Luijk &
    Govers, 1992).

         Macro-pyrolysis experiments were performed in a quartz tube
    reactor.  The ABS sample was inserted in the pre-heated tube and
    exposed at 400-700°C for 20 min.  The carrier gas was nitrogen,
    nitrogen with 5% oxygen, or, nitrogen with 10% oxygen.  In a nitrogen
    atmosphere, predominantly mono- to pentabromodibenzofuran were formed
    at µg/kg levels.  In the presence of oxygen, the yield of PBDF was
    increased.  Although the formation of PBDD has been shown in an oxygen
    atmosphere, the yield of PBDD was lower than that of PBDF.  At 600°C,
    a maximum yield of both PBDD and PBDF was found.  At 700°C, a shift
    towards lower brominated compounds was observed.  In neither of the
    samples were 2,3,7,8-substituted isomers detected.  The results are
    summarized in Table 2 (Luijk & Govers, 1992).

         Thies et al. (1990) pyrolysed commercial TBBPA-containing
    polymers at 600°C under 3 different test conditions.  Pyrolysis of
    polymer 1 (ABS/16% TBBPA/6% Sb2O3) produced a total of
    approximately 1500, 150, 3000 µg PBDD/DF/kg in the three tests,
    relative to the original sample weight.  The pyrolysis products of two
    further polymers (TBBPA/bisphenol A - copolycarbonate (PC) + 10%
    copolymerized TBBPA and ABS/TBBPA/bisphenol A - polycarbonate blend
    + 6% copolymerized TBBPA) gave predominantly mono- to tribrominated
    PBDD and PBDF in the range of 100-5000 µg/kg.  No 2,3,7,8-substituted
    isomers were detected (detection limits 1-4 µg/kg) with the exception
    of one sample, which showed 4 µg 2,3,7,8-TBDD/kg and 2 µg
    2,3,7,8-TBDF/kg.


        Table 2.  The yields of PBDF and PBDD during pyrolysis of ABS/TBBPA in µg/kg relative to blenda

    (a) PBDF

                                                                                               

    Temperature (°C)    MBDFb               DiBDFb         TrBDFb         TeBDFb         PeBDFb
                                                                                               

    NITROGEN

    400                 10 (3)              35 (25)        6 (4)          4 (2)          13 (2)
    500                 50 (43)             30 (7)         11 (3)         13 (3)         15 (5)
    600                 10                  170            50             80             80
    700                 n.d.                840            50             50             n.d.

    NITROGEN + 5% OXYGEN

    400                 10                  25             3              10             10
    500                 5                   40             15             50             50
    600                 10 (1)              925 (75)       200 (60)       100 (50)       50 (25)
    700                 200 (150)           2250 (650)     230 (30)       15 (4)         4 (2)

    NITROGEN + 10% OXYGEN

    400                 n.d.                55             15             20             n.d.
    500                 20                  190            15             15             20
    600                 265 (115)           1550 (1000)    220 (80)       70 (35)        35 (20)
    700                 130                 2400           420            85             35

    (b) PBDD

    NITROGEN

    400                 n.d.                n.d.           0.05 (0.05)    n.d.           n.d.
    500                 n.d.                0.5 (0.5)      0.5 (0.1)      n.d.           n.d.
    600                 2                   5              2              n.d.           n.d.
                                                                                               

    Table 2 (cont'd)
                                                                                               

    Temperature (°C)    MBDFb               DiBDFb         TrBDFb         TeBDFb         PeBDFb
                                                                                               

    NITROGEN + 5% OXYGEN

    400                 1                   1              1              n.d.           n.d.
    500                 3                   15             15             n.d.           n.d.
    600                 5 (1)               250 (0)        145 (5)        3 (0.5)        n.d.
    700                 100 (80)            225 (75)       35 (5)         n.d.           n.d.

    NITROGEN + 10% OXYGEN

    400                 n.d.                2              5              1              n.d.
    500                 6                   70             40             2              n.d.
    600                 6 (1)               225 (155)      220 (0)        6 (0.1)        n.d.
    700                 5                   75             30             n.d.           n.d.
                                                                                               

    a  From: Luijk & Govers (1992).
    b  n.d. = not detected.
    

    4.3.3  Extrusion experiments with TBBPA-containing polymers

         A sample of ABS/16% TBBPA/6% Sb2O3 was heated to 240°C for
    20 min (Thies et al., 1990).  In one test run, 100 µg/kg mono- and
    di-BDF were found in the post-extrusion resin, in the second run, less
    than 17 µg/kg were found.  No 2,3,7,8-substituted PBDD/F were detected
    (detection limit 10 µg/kg).

         Craig et al. (1989) carried out a study to determine whether
    brominated flame retardants and/or brominated dibenzodioxins and
    dibenzofurans were present in the fumes emitted during the thermal
    processing of resins.  Thermal processing (heat treatment) involved
    extrusion of pelletized Cycolac resin formulated with, or without,
    TBBPA, under conditions considered to be representative of customer
    use.  The measured die-zone and extrusion temperatures were 232 and
    215°C, respectively.  A mass balance was obtained by analysing the
    residues in the pelletized extruder feed material (pre-extruded
    resin), in the heat-treated plastic resin (post-extruded resin), and
    in the fumes that were evolved during thermal processing.  The results
    are summarized in Table 3.


    Table 3.  Total concentration of PBDD/PBDF (µg/kg)a
                                                                        

    Flame         Pre-extrusion       Post-extrusion        Fumesb
    retardant         resin               resin
                                                                        

                 PBDF      PBDD      PBDF      PBDD      PBDF     PBDD
                                                                        

    TBBPA        1.09      n.d.c     n.d.c     6.16      0.020    0.006
                (1.09)d
                                                                        

    a  From: Craig et al. (1989).
    b  Fumes expressed as µg/kg of extruded resin.
    c  n.d. = Not detected (Detection limit 0.0002-0.075 µg/kg for PBDD
       and 0.002-0.205 µg/kg for PBDF).
    d  Total concentration of 2,3,7,8-substituted isomers.


         Low levels of PBDF and PBDD were present in the pre- and
    post-extruded resin and in the fumes.  The concentrations of
    identified 2,3,7,8-substituted isomers formed from TBBPA were
    just above the limit of detection.

    4.3.4  Reports on fires involving TBBPA

         A large-scale fire occurred in a storage area of a plastics
    production plant in Germany.  Besides a great quantity of poly-
    carbonate (PC) and polybutylene terephthalate (PBT), 180 tonnes of
    flame-retarded PBT were also burnt in the fire.  The flame-retarded
    PBT contained TBBPA or its polymeric derivatives as a bromine carrier. 
    Four samples of the mostly burnt PBT material and one sample of
    ash/slag mixture were examined for the presence of PBDF/PBDD residues. 
    Three samples of soil were also analysed.  One of the three soil
    samples was collected at a distance of 1460 m, one at 1340 m, and the
    third sample at a distance of 1740 m from the fire.  The four samples
    of burnt PBT material and the ash/slag samples were analysed for the
    presence of 2,3,7,8-substituted tetra-, penta-, and hexa-BDF/BDD
    (eight congeners).  The maximum concentrations detected were 0.5 µg/kg
    (detection limit 0.2-5 µg/kg).  The three soil samples were analysed
    for the same congeners and concentrations of < 0.5 (detection limit)
    and 1.0 ng/kg were found (Neupert & Pump, 1992).

    4.4  Ultimate fate following use

    4.4.1  Disposal

         It must be assumed that the majority of articles flame-retarded
    with TBBPA are ultimately disposed of either in landfills or
    incinerators.

    4.4.2  Recycling of TBBPA-containing polymers

         Studies on the reprocessability of selected samples of flame-
    retarded office machines have shown that those based on TBBPA can be
    recycled (Meyer et al. 1993).  The materials tested were mainly flame-
    retarded ABS and PC-ABS polymer blends (mostused in office machines). 
    Samples were tested from each of the following: granulated form,
    newly-produced parts, used parts with exact specification as to flame
    retardant, and two mixed used samples with unknown flame retardant
    from dismantled office machines.  The samples were analysed for their
    contents of the 2,3,7,8-substituted congeners of polybrominated
    dibenzodioxins and furans (PBDD/PBDF) using 13C internal standards
    of these isomers.  Detection was by low resolution, and, for some
    samples, high resolution mass spectrometry.  ABS samples with TBBPA
    contained only traces (less than 5 µg/kg) of these dioxin and furan
    isomers, even after 5 recyclings.

         Lorenz & Bahadir (1993) investigated the recycling of printed
    circuits containing TBBPA, which is normally used in products of the
    German printed circuits industry.  In the pilot recycling plant, a
    test run was carried out using a hammer mill and an impact grinder. 
    No halogenated dibenzodioxins and dibenzofurans could be detected on
    the filters of active air sampling behind the filter devices of the
    mills. The shredded material was contaminated with PBDD/PBDF at low

    concentrations of 0.03-1.13 ng/g.  In a test with printed circuits
    under thermal stress (up to 300°C in an oven), low amounts of
    PBDD/PBDF (0.74-4.52 ng/g) were generated.  The authors concluded that
    printed circuits containing TBBPA can be recycled.

    5.  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    5.1  Environmental levels

    5.1.1  Air

         The air near production facilities in Southern Arkansas, USA,
    contained 1.8 µg TBBPA/m3 (Zweidinger et al., 1979).

    5.1.2  Water

         In 1977, in Japan, none of 15 water samples analysed contained
    TBBPA (limit of determination, 0.02-0.04 µg/litre). Water samples were
    collected in 25 areas in Japan in 1986-87.  TBBPA was detected in one
    out of three water samples from the mouth of the Yamato River
    (Environment Agency Japan, 1989).  In 1987, in Japan, TBBPA was
    detected in one out of 75 water samples at a concentration of
    0.05 µg/litre (limit of determination, 0.03 µg/litre).  In 1988-89, in
    Japan, TBBPA was not detected in 150 water samples collected at 50
    locations (limit of determination, 0.04 µg/litre) (Environment Agency
    Japan, 1989, 1991).

    5.1.3  Soil

         TBBPA was detected at 0.5-140 µg/kg (dry weight) in 14 out of 19
    river sediment samples in Osaka, Japan. In marine sediments in Osaka
    bay, levels of 0.5-4.5 µg/kg (dry weight) were found in 1981-83.  In
    the marine sediments of two areas other than Osaka, the levels were
    much lower (n.d.-1.8 µg/kg dry weight).  The dimethylated metabolite
    of TBBPA was found in 5 out of 6 samples of river sediment, collected
    in the Osaka area in 1983, in concentrations of 0.6-1.8 µg/kg wet
    weight (Watanabe et al., 1983a,b; Watanabe & Tatsukawa, 1990).  A
    river sediment was collected in 1981 downstream of the Neya River,
    from a tributary of the Yodo River, which empties into the Osaka Bay.
    The TBBPA concentration was about 20 µg/kg dry weight (Watanabe et
    al., 1983a,b).

         Sediment samples were collected in 22 areas, in Japan, in 1987. 
    TBBPA was found in the bottom sediments from 6 areas; the mouth of the
    Sumida River (3/3), the mouth of Ara River (1/3), the mouth of Yamato
    River (3/3), the river flowing in Osaka City (3/3), the Port of Osaka
    (3/3) and the mouth of Yodo River (1/3).

         TBBPA was detected in 14 out of 66 sediment samples at
    concentrations ranging from 2 to 150 µg/kg dry weight and it was
    detected in 20 out of 130 sediment samples collected at 44 locations

    at concentrations ranging from 2 to 108 µg/kg dry weight in the 1988
    (limit of determination in both studies: 2 µg/kg dry weight)
    (Environment Agency Japan, 1989, 1991).

         Sellström et al. (1990) analysed sediment samples taken upstream
    and downstream from a factory in Sweden for the presence of TBBPA and
    its dimethylated derivative (Me2-TBBPA).  The downstream level of
    TBBPA was 430 µg/kg (ign. loss) and upstream, 50 µg/kg, the levels of
    the dimethylated compound were 2400 µg/kg (ign. loss) and 36 µg/kg,
    respectively.

    5.1.4  Fish and shellfish

         TBBPA was not detected in mussels  (Mytilus edulis) collected in
    Osaka bay in 1981.  Two out of 19 samples of fish and shellfish,
    collected in the Osaka area, contained 0.8 and 4.6 µg methylated
    TBBPA/kg wet weight, respectively (Watanabe & Tatsukawa, 1990).

         When 75 fish samples were collected in 24 areas in Japan in 1987,
    no TBBPA was detected (Environment Agency Japan, 1989).  TBBPA was
    also not detected in 135 samples collected at 45 different locations
    in Japan in 1988 (limit of determination, 1 µg/kg wet weight)
    (Environment Agency Japan, 1991).

    5.2  General population exposure

         The dimethylated metabolite of TBBPA was not found in 5 fat
    samples collected from people living in the Osaka area (limit of
    determination, < 20 µg/kg fat) (Watanabe & Tatsukawa, 1990).

    5.3  Occupational exposure

         There are no data on TBBPA occupational exposure levels.

         Investigations into the possible formation of PBDD/PBDF during
    processing have been described in section 4.3.3.

         Thies et al. (1990) monitored the workplace atmosphere near the
    system for manually controlling an injection moulding machine, when
    processing a polymer formulation (ABS + 16% TBBPA/6% antimony
    trioxide).  Two samples were taken at 4.3 and 4.8 m3.  At detection
    limits of 0.1 and 1 ng/m3 respectively, no 2,3,7,8-PBDD/PBDF isomers
    or PBDD/PBDF were detectable.

    6.  KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS

    6.1  Absorption and elimination

    6.1.1  Mammals

         A single oral dose (6.51-7.55 mg/kg body weight) of 14C TBBPA
    (phenyl UL-14C) in corn oil was poorly absorbed from the gastro-
    intestinal tract of Sprague-Dawley rats.  About 95% of 14C-labelled
    material was eliminated in the faeces and less than 1.1% in the urine
    within 72 h.  The highest tissue levels were found in the liver and in
    the gonads.  Tissue half-lives were reported to be 19.9 h in the blood,
    70.8 h in fat, 17.1 h in the kidneys, 10.8 h in the liver, 39.3 h in
    the spleen, 48.0 h in muscle, and 60.5 h in the gonads.  The maximum
    half-life in any tissue is less than 3 days (Brady, 1979).

    6.1.2  Fish and shell-fish

         When bluegill sunfish (Lepomis macrochirus) were exposed to
    labelled 14C-TBBPA in the water at a concentration of
    0.0098 mg/litre, they showed rapid uptake of TBBPA. Equilibrium was
    reached within 3 days.  The 14C in the fish was rapidly eliminated
    on transfer to uncontaminated water.  The half-life of elimination was
    less than 24 h in both edible and non-edible tissues.  The residues
    decreased below the limit of detection (< 0.01 mg/kg) in 3-7 days
    (Nye, 1978) (see also section 4.2.4).

         TBBPA was not detected in mussels  (Mytilus edulis) collected at
    the seashore in Osaka Bay in 1981.  However, a 4.4'-dimethoxy
    derivative of TBBPA was identified in the mussel at a concentration of
    5 µg/kg wet weight (Watanabe et al., 1983a).

    6.2  Metabolism

         No data are available.

    7.  EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS

    7.1  Single exposure

    7.1.1  Oral

         Gustafsson & Wallen (1988) reported oral LD50s of > 2 g
    TBBPA/kg body weight in rats and 3.2 g/kg body weight in mice.

         TBBPA was administered to a group of 10 rats (5 male, 5 female)
    at a single dose of 5000 mg/kg.  The animals were observed for 14
    days.  No mortality occurred during the observation period.  No gross
    lesions were detected at necropsy.  The rat oral LD50 was
    > 5000 mg/kg (Hardy, 1994).

         The LD50 in B6C3F1 mice was reported to be 4.4 g/kg and
    4.5 g/kg in male and female mice, respectively (Sekizawa, personal
    communication, 1994).

    7.1.2  Dermal

         TBBPA was applied to the clipped, intact skin of albino rabbits
    at concentrations of up to 3.16 g/kg body weight, for 24 h.  No local
    or systemic symptoms could be detected by clinical observation,
    urinalysis, haematology, weight gain, or gross pathology (Great Lakes
    Chemical Corporation, 1986, summary report).

         The LD50 of TBBPA in guinea-pigs was > 1 g/kg body weight
    (Bayer, 1990, summary report).

         TBBPA was applied at a dose level of 2000 mg/kg to 10 rabbits
    (5 male, 5 female).  The test material was applied on abraded skin,
    covered, and left in contact for 24 h.  The animals were observed for
    14 days.  No mortality occurred during the observation period.  Slight
    erythema and oedema were observed in 1 rabbit on day 1.  No gross
    lesions were detected at necropsy.  The rabbit dermal LD50 is
    > 2000 mg/kg (Hardy, 1994).

         When 10 female rabbits were dermally exposed to TBBPA at a dose
    of 200 mg/kg body weight, all rabbits exhibited reddening of the skin
    that returned to normal in 48 h.  None of the rabbits died.  The
    LD50 was > 200 mg/kg.  In another study, the intact or shaven skin
    of groups of 2 rabbits was exposed to a dose of 1, 2.15, 4.64, or
    10 g/kg body weight for 24 h.  Weight loss was seen at the two highest
    dose levels.  Only one rabbit died in the 1 g/kg group and one in the
    4.64 g/kg group (Bayer, 1990 - summary report).

    7.1.3  Inhalation

         Groups of 10 Wistar rats, 10 NMDI-mice, and 10 guinea-pigs (five
    of each sex/group) were exposed for 8 h to a concentration of 0.5 mg
    TBBPA aerosol/litre air and observed for 48 h after exposure.  None of
    the animals showed symptoms of local or systemic toxicity.  There were
    no gross pathological findings at autopsy (Sterner, 1967).

    7.2  Short-term exposures

    7.2.1  Oral (rat)

         Groups of 25 female and 25 male Charles River CD rats (males
    260-341 g, females 183-232 g) were fed dietary levels of 0, 1, 10,
    100, or 1000 mg TBBPA/kg (corresponding to 0, 0.05, 0.5, 5, or
    50 mg/kg body weight per day) for 28 days.  After 4 weeks, 5 rats/sex
    per group were sacrificed and the remaining rats placed on control
    diets for 2, 6, or 12 weeks.  No effects on behaviour, appearance,
    food consumption, body weight gain, or mortality were observed.  No

    gross or microscopic abnormalities were observed.  Total bromine
    levels were determined in the liver and fat of rats from the control
    group and the highest dose group sacrificed at the end of the 28-day
    feeding period.  No differences in bromine contents were seen
    (Goldenthal & Geil, 1972).

         Groups of 7 male and 7 female Sprague-Dawley rats (6-7 weeks
    old), (control and 3 mg/kg groups consisted of 21 male and 21 female
    animals) were fed a diet supplying 0, 0.3, 3, 30, or 100 mg TBBPA/kg
    body weight for 90 days.  The concentrations in the diet were adjusted
    weekly to deliver the above doses.  The toxicological parameters
    evaluated were appearance, demeanour, body weight gain, food
    consumption, haematology, clinical chemical determinations,
    urinalysis, organ weights, and gross- and microscopic examinations. 
    The administration of TBBPA in the diet at a dose as high as 100 mg/kg
    body weight per day for 90 days did not produce toxicological effects. 
    On days 10, 20, 30, 60 and 90, liver, kidneys, skeletal muscle, fat
    and serum of 2 control animals and 2 animals of the 3 mg/kg group were
    analysed for bromine.  The total bromine content in the tissues of
    rats receiving 3 mg/kg per day did not differ from that of the
    controls.  Higher dose levels were not tested (Quast et al., 1975).

         In a Japanese study (Tobe et al., 1986), B6C3F1 mice (10/sex per
    group) were fed TBBPA in the diet at 0, 500, 4900, 15 600, or
    50 000 mg/kg (corresponding to 0, 71, 700, 2200, or 7100 mg/kg body
    weight per day, respectively) for 3 months.  All animals at the
    highest dose died during the study, probably because of malnutrition
    and anaemia.  No deaths were observed at lower doses. Body weight
    gains were decreased at levels of 15 600 mg/kg and higher, though food
    intake did not change.  Red blood cells, haemoglobin, haematocrit,
    serum triglycerides, and total serum proteins decreased at
    15 600 mg/kg.  Organ weight changes and pathological changes were not
    detected, except in the spleen, where organ weight increased and some
    blood was observed outside the medulla.  These effects may have been
    related to the haemorrhage observed in this study and the uncoupling
    of energy production in mitochondria observed by Inouye et al. (1979). 
    The NOAEL was 4900 mg/kg diet (corresponding to 700 mg/kg body weight
    per day).

    7.2.2  Inhalation (rat)

         Four groups of 5 female and 5 male Charles River CD rats (males
    260-334 g, females 213-248 g) were exposed to an atmosphere of 0, 2,
    6, or 18 mg micronized TBBPA/litre air (0, 2000, 6000, or
    18 000 mg/m3) for 4 h daily, 5 days/week, for 2 weeks.  Body weights
    and food consumption were recorded weekly.  Haematological and
    biochemical examinations and urinalysis were carried out just before
    the rats were sacrificed.  Excessive salivation, red or clear nasal
    discharge, and excessive lacrimation were noted during the course of
    the study for rats at the two highest dose levels.  There were no
    deaths and no changes in body weight gain, food consumption,

    haematological and biochemical parameters, or urinalysis.  A decrease
    in relative liver weight of the female animals from the three dose
    levels might have been compound related.  No gross or microscopic
    lesions were seen in any of the rats at the end of the study
    (Goldenthal et al., 1975).

    7.2.3  Dermal (rabbit)

         Dosages of 100, 500, or 2500 mg TBBPA/kg body weight were applied
    to the backs of New Zealand white rabbits (2030-2311 g), for 6 h/day,
    5 days a week, for 3 weeks.  Four male and four female rabbits were
    used at each dose level and also in the control group.  The control
    group received 0.9% physiological saline.  The back of each rabbit was
    clipped with an electric clipper and the skin of one-half of the
    rabbits in each group was abraded twice each week.  No mortality or
    signs of overt toxicity were observed.  Very slight skin erythema was
    observed occasionally at the low dose and, for almost all rabbits for
    various lengths of time, at the two higher dose levels.  Body weight
    gain, haematological parameters, urinalysis, organ weights, and gross
    and microscopic examinations did not reveal any compound-related
    changes (Goldenthal et al., 1979).

    7.3  Long-term exposure

         No data on this subject are available.

    7.4  Skin and eye irritation; sensitization

    7.4.1  Skin irritation

         The studies conducted in which rats were administered TBBPA did
    not reveal skin irritation (Quast et al., 1975).

         Three male and three female rabbits were administered 500 mg
    TBBPA on the intact and shaven skin for 24 h.  No skin irritation was
    observed. In another study, six rabbits were exposed to 500 mg on
    intact and shaven skin for 24 h, no deaths occurred (Bayer, 1990,
    summary report).

         TBBPA was applied to 2 intact and 2 abraded skin sites on each of
    6 rabbits (3 males, 3 females).  The application site was covered for
    24 h.  Observations were recorded 24 and 72 h after exposure.  Scores
    for all animals for all readings were zero.  TBBPA was non-irritating
    to the skin (Hardy, 1994).

    7.4.2  Eye irritation

         TBBPA was instilled into the right eye of six rabbits (3 males,
    3 females).  Four of the rabbits exhibited slight redness at the 1-h
    observation period (four scores of Grade 1 in the conjunctiva).  No
    other ocular reactions were observed during the study.  TBBPA was
    non-irritating to the eye (Hardy, 1994).

         Single doses of 3 mg of finely ground TBBPA were applied to the
    conjunctival sac of the eye of New Zealand White rabbits (2.5 kg). Eye
    examinations were carried out, 5 min, and 1 and 4 h after the
    application, and daily thereafter for 7 days.  No effects on the
    cornea, iris, or conjunctiva using Draize score were observed at any
    time.  The rabbits exhibited normal appearance and behaviour, gained
    weight normally, and showed no evidence of systemic toxicity.  There
    were no gross pathological findings at autopsy.  It was concluded that
    TBBPA was not irritating to the eye (Sterner, 1967).

    7.4.3  Sensitization

         Twelve male, albino guinea-pigs (596-700 g) were divided into two
    groups consisting of a positive control group (dinitrochloro-benzene)
    of 4 guinea-pigs and a treated group of 8 guinea-pigs.  The compounds
    were injected intradermally every other day, 3 times/week, up to a
    total of 10 doses in the back and flanks of the guinea-pigs.  TBBPA
    was applied at a concentration of 0.1% TBBPA in 0.9% NaCl solution. 
    The solvent was applied to all animals in the other flanks.  Two weeks
    after the 10 injections, a challenge dose was administered
    intradermally.  The result of the TBBPA challenge injection was
    negative.  No sensitization reaction was found (Dean et al., 1978b).

         TBBPA was applied dermally to 10 guinea-pigs for a total of 9,
    six-h insult periods.  A positive control group consisting of 10
    guinea-pigs was treated with 2,4-dinitrochlorobenzene.  Approximately
    14 days after the last sensitizing exposure, the animals were
    challenged in the same manner at both the site of sensitization and a
    second site.  A second challenge was made 48 h after the first
    challenge.  A positive response was elicited by the positive control
    substance.  No irritation was observed during induction or challenge
    with TBBPA.  TBBPA was not a sensitizer in this guinea-pig
    sensitization test (Hardy, 1994).

    7.4.4  Chloracnegenic activity

         TBBPA was inuncted in one ear of each of 4 rabbits (2 males and 2
    females) at concentrations of 0.5, 5, or 50% in Polylan.  The
    substance was administered once daily, 5 days/week, for 4 weeks. 
    Observations were recorded at time 0, and on days 7, 14, 21, and 28. 
    No positive scores were recorded for concentrations of 5 and 50%.  One
    rabbit exhibited a slight response (grade 1) at the 0.5% concentration

    on day 7. No other positive reactions were observed.  No gross lesions
    were recorded at necropsy.  TBBPA was noncomedogenic in the rabbit ear
    assay (Hardy, 1994).


    7.5  Reproductive toxicity, embryotoxicity, and teratogenicity

    7.5.1  Teratogenicity

         TBBPA was administered, by gavage, at dose levels of 0, 30, 100,
    300, 1000, 3000, or 10 000 mg/kg body weight, on gestation days 6-15,
    to groups of 5 Charles River CD female rats (15 weeks old).  The rats
    were sacrificed on gestation day 20.  Three out of 5 rats given
    10 000 mg/kg died, while the remaining rats in this group showed a
    slight decrease in body weight gain between gestation days 6 and 15;
    green, soft stools; and an increase in matted hair in the anogenital
    area.  There were no signs of toxicity in rats administered levels up
    to, and including, 3000 mg/kg.  There were no differences in the mean
    numbers of viable or nonviable fetuses, resorptions, implantations, or
    corpora lutea compared with the controls (Goldenthal et al., 1978).

         In another study, rats were treated with 0, 0.28, 0.83, or 2.5 g
    TBBPA/kg body weight from day 0 to day 19 of gestation.  The
    treatments did not impair the birth rate.  No toxic effects were
    observed on the embryo or fetus, and there were no skeletal or
    visceral abnormalities.  The postnatal development was not impaired
    (Noda, 1985).

    7.6  Mutagenicity and related end-points

         A mutagenicity study was conducted on  Salmonella typhimurium
    TA1535, TA1537, TA1538, TA98 and TA100 and on  Saccharomyces
     cerevisiae strain D4, with, and without, metabolic activation with
    liver S9 fraction of Aroclor 1254-induced male Sprague-Dawley rats. 
    Positive controls were used for comparison.  The dose levels of TBBPA
    were 0, 0.25, 0.5, 5.0, and 50 µg/plate in DMSO.  No mutagenic
    activity was found in this assay (Brusick, 1976).

         TBBPA was examined for mutagenic activity at concentrations of
    0.001, 0.003, 0.01, 0.03, and 0.1 mg/plate in a series of  in vitro
    microbial assays using  Salmonella typhimurium TA1535, TA1537,
    TA1538, TA98, and TA100 and  Saccharomyces cerevisiae with, and
    without, microsomal enzyme preparations from Aroclorinduced rats.  All
    tests with, and without, the liver activation system were negative
    (abstract only) (Great Lakes Chemical Corporation, 1986).

         Mortelmans et al. (1986) tested TBBPA for mutagenic potential in
     Salmonella typhimurium strains TA100, TA1535, TA1537, and TA98 in
    concentrations of 0, 100, 333, 1000, 3333, and 10 000 µg/plate with,

    and without, S9 mix of Aroclor 1254-treated, male Sprague-Dawley rats
    and male Syrian hamsters.  The substance was dissolved in DMSO.  TBBPA
    did not show mutagenic potential.

         Ethyl Corporation also reported that TBBPA was negative in
    several Ames assays in 5 strains both with and without exogenous
    metabolic activation (Hardy, 1994).

    7.7  Carcinogenicity

         No data are available on this subject.

    7.8  Other special studies

         The  in vitro effect of TBBPA on the function of biological
    membranes was examined.  Human erythrocytes or rat mitochondria were
    tested with TBBPA at 25-250 µmol/litre. The data indicate that TBBPA
    primarily alters the permeability of membranes, resulting in
    haemolysis of erythrocytes accompanied by morphological changes and
    uncoupling of the mitochondrial oxidative phosphorylation (Inouye et
    al., 1979).

         In rats, after a single dose (oral or ip) of TBBPA, moderate
    microsomal enzyme-inducing activity was observed in the liver but not
    in the small intestine (Gustafsson & Wallen, 1988). 

    8.  EFFECTS ON HUMANS

         TBBPA mixed with water to produce a thick slurry of a paste-like
    consistency (approximately 3-5 mg) was applied 10 times to the upper
    arms of 13 male and 41 female volunteers during the sensitization
    phase.  A modified Draize multiple insult test was conducted which was
    followed after 10-14 days by the challenge treatment.  TBBPA did not
    produce any skin irritation and did not show any evidence of contact
    sensitization in the subjects who completed the study (Dean et al.,
    1978a).

    9.  EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

    9.1  Laboratory studies

         It should be noted that results of studies performed at pHs close
    to the pKa values (7.5 and 8.5, respectively) may be difficult to
    extrapolate outside this range.

    9.1.1  Microorganisms

    9.1.1.1  Water

         Marine unicellular algae,  Skeletonema costatum, Thalassiosira
     pseudonana, and  Chlorella sp., were exposed to TBBPA in 6 algal
    growth media.  The duration of the exposure for  S. costatum and
     T. pseudonana was 72 h, and, for  Chlorella sp., 96 h.  The
    population density was estimated by cell counts on a haemacytometer. 
    Growth of  Chlorella sp. was not inhibited by as much as 50% by
    1500 µg/litre of TBBPA. TBBPA was toxic for  S. costatum and
     T. pseudonana, the EC50s being between 90-890 µg/litre and
    130-1000 µg/litre, respectively (Walsh et al., 1987).

         The freshwater green alga,  Selenastrum capricornutum (5-day-old
    inoculum) was used to test TBBPA (prepared with distilled deionized
    water) at measured concentrations of 0.34, 0.76, 1.5, 3.0, and
    5.6 mg/litre (nominal concentrations 0.6, 1.2, 2.4, 4.8, and
    9.6 mg/litre)a.  The conditions of the test were, temperature
    20-24°C, constant illumination, shaking at 100 rpm, and pH 7.5.  The
    effect criterion was reduction in cell density relative to the
    control.  Growth of  S. capricornutum was not reduced by 96 h of
    exposure to TBBPA at any dose level (Giddings, 1988).

    9.1.1.2  Soil

         TBBPA was tested in two strains of bacteria capable of carrying
    out the  O-methylation of phenolic compounds.  The strains were;
    strain 1395 (Gram-positive  Rhodococcus sp.) and strain 1678
    (Gram-negative  Acinetobacter sp.).  Three ml of cell suspension was
    used in a 28-ml serum bottle.  TBBPA was  O-methylated only by the
    Gram-positive strain.  It was suggested that, in the natural
    environment, bacterial  O-methylation of phenols carrying electron-
    attracting substituents might be a significant alternative for
    biodegradation (Allard et al., 1987).

    9.1.2  Aquatic organisms

    9.1.2.1  Invertebrates

         The 48-h, acute LC50 for  Daphnia magna (less than 20 h old)
    was 0.96 mg TBBPA/litre; at the lowest concentration studied
    (0.32 mg/litre), 5% of the organisms died.  The water conditions were:
    temperature 17.5°C, pH 7.32, and total hardness and total alkalinity,
    64 and 32 mg/litre, respectively (Morrissey, 1978).

                 

    a  0.72-4.16 mg/litre reported for the water solubility, but it may
       be pH-dependent.

          Daphnia magna were continuously exposed (flow-through system)
    for 21 days to measured concentrations of 0.056, 0.10, 0.19, 0.30, and
    0.98 mg TBBPA (99.15%)/litre.  Well water was used with a total
    hardness of 170 mg/litre and an alkalinity of 120 mg/litre (both as
    CaCO3), pH 8.1-8.2, temperature 20°C, and dissolved oxygen of
    8.0-8.7 mg/litre.  At the termination of the study, daphnid survival
    at all concentrations ranged from 95 to 100%, which was comparable
    with the 98% survival of control organisms.  Daphnid growth, as
    determined by the measurement of individual body lengths at the end of
    the test, was also not adversely affected by any of the test
    concentrations.  Reproduction, as determined by cumulative numbers of
    offspring per female at test termination, was the most sensitive
    indicator of toxicity of TBBPA for  Daphnia magna in the
    concentration range tested.  Reproduction in 0.98 mg/litre was 21
    offspring per female, which was significantly less than the
    reproduction of the pooled control organisms (60 offspring per
    female).  Reproduction at the remaining test concentrations was
    statistically similar to that of the pooled control organisms.  The
    Maximum Acceptable Toxicant Concentration (MATC) for  Daphnia magna
    was > 0.30 and < 0.98 mg/litre (geometric mean 0.54 mg/litre)
    (Surprenant, 1989b).

         Steinberg et al. (1992) showed that dissolved humic material had
    no effect on the toxicity of TBBPA for  Daphnia magna (inhibition of
    motility; 48 h; 20°C).

         Goodman et al. (1988) exposed Mysid shrimp  (Mysidopsis bahia),
    aged < 1, 5, and 10 days old, to TBBPA in a flow-through system for
    96 h.  The test conditions were: mean salinity 20.6%, pH 7.96-8.16,
    and mean dissolved oxygen concentration 6.9 mg/litre. The TBBPA was
    dissolved in a mixture of triethylene glycol and acetone.  The 96-h
    LC50 values for the three live stages were 860(670-1200), 1100, and
    1200 µg TBBPA/litre, respectively.

         The acute EC50, defined as reduction of shell deposition, was
    determined in Eastern oysters  (Crassostrea virginica) in a flow-
    through system (oysters had a mean valve height of 41 mm).  The mean
    measured test concentrations were 0.018, 0.032, 0.051, 0.087, and
    0.150 mg TBBPA/litre.  Salinity range was 29-32%, dissolved oxygen
    ranged from 86 to 95% of saturation, pH 8.0-8.1. The 96-h EC50 was
    calculated to be 0.098 mg TBBPA/litre with a noobserved-effect
    concentration below 0.018 mg/litre.  An estimated NOEC of
    0.0062 mg/litre was calculated (Surprenant, 1989c).

    9.1.2.2  Fish

         The 96-h, acute LC50 of TBBPA for bluegill sunfish  (Lepomis
     macrochirus; 6 months old, length 38 mm, weight 0.59 g) was
    0.51 mg/litre (nominal concentration), in a static system.  The
    conditions of the water were: temperature 21.7°C, pH 7.47, and total
    hardness and total alkalinity, 44 mg/litre and 33 mg/litre as CaCO3,

    respectively.  With dose levels above 0.32 mg/litre, the fish became
    irritated and exhibited abnormal sounding and skittering swimming
    behaviour.  The no-effect level was 0.10 mg/litre (Calmbacher, 1978a).

         The 96-h LC50 of TBBPA for rainbow trout (Salmo gairdneri;
    3 months old, length 41 mm, weight 0.51 g) was 0.40 mg/litre (nominal
    concentration) in a static system.  The conditions of the water were:
    temperature 12.3°C, pH 7.48, total hardness and total alkalinity, 40
    and 35 mg/litre as CaCO3, respectively).  The no-effect level was
    0.18 mg/litre.  With higher levels, the fish became irritated and
    exhibited twitching, erratic swimming, dark discoloration, and
    laboured respiration (Calmbacher, 1978b).

         The LC50 of TBBPA for fathead minnow ( Pimephales promelas;
    mean wet weight 0.50 g and total length 36 mm) (20 fish/group) was
    determined under flow-through conditions. The total duration of the
    study was 144 h.  Well-water was used with total hardness and
    alkalinity ranges of 22-30 and 21-24 mg/litre, as CaCO3,
    respectively.  The pH was 6.7-7.1, the dissolved oxygen concentration
    range, 91-96% of saturation, and the temperature 21-22°C.  The mean
    measured test concentrations were 0.19, 0.26, 0.32, 0.45, and
    0.63 mg/litre.  The 96-h LC50 was determined to be 0.54 mg/litre
    with a no-observed-effect concentration of 0.26 mg/litre (Surprenant,
    1988).

         Fathead minnow  (Pimephales promelas) embryos and larvae were
    continuously exposed for 35 days (30 days post-hatch) to mean,
    measured TBBPA concentrations ranging from 0.024 to 0.31 mg/litre. 
    The water quality was: mean total hardness 28-29 mg/litre and
    alkalinity 23-24 mg/litre (both as CaCO3), pH 7.0-8.2, temperature
    24°C, and mean dissolved oxygen 8.1-8.6 mg/litre.  Observations were
    made on the survival of organisms at hatch, and survival and growth
    (wet weight and total length) of larvae after 30 days post-hatch
    exposure.  The survival at the end of the hatching period (day 5) at
    the highest concentration of 0.31 mg/litre was 28% and was
    significantly less than survival in the control organisms, 84% (pooled
    control and solvent control data).  The survival of embryos exposed to
    mean concentrations of 0.16, 0.084, 0.040, and 0.024 mg/litre ranged
    from 74 to 90% and was unaffected compared with the control embryos. 
    All larvae exposed to 0.31 mg/litre died within the initial 7 days of
    the post-hatch exposure period.  The survival of larvae exposed to the
    remaining concentrations of TBBPA (0.16-0.024 mg/litre) ranged from 87
    to 93% and was comparable to survival in the control larvae (93%).  At
    test termination (30 days post-hatch), growth data (total length and
    wet weight) established that surviving fish at all treatment levels
    grew at rates comparable to those of the control larvae.  The mean
    length and wet weight of larvae exposed to the mean, measured TBBPA
    concentration of 0.16 mg/litre ranged from 24 to 25 mm and 112 to
    126 mg, respectively, and were statistically comparable to those of

    control larvae (pooled data, 25 mm and 111 mg, respectively).  On the
    basis of adverse effects on embryo and larval survival, the Maximum
    Acceptable Toxicant Concentration (MATC) of TBBPA for fathead minnow
    was estimated to be > 0.16 mg/litre and < 0.31 mg/litre (geometric
    mean 0.22 mg/litre) (Surprenant, 1989a).

    9.1.3  Sediment-dwelling organisms

         A study with a benthic invertebrate midge,  Chironomous tentans
    (25 per replicate vessel) consisted of three, 14-day (partial life
    cycle) toxicity tests under flow-through conditions.  Each of the
    sediment tests was conducted with sediment containing different levels
    of organic carbon.  The water quality was: mean total hardness and
    total alkalinity 29-30 and 25-28 mg/litre as CaCO3, pH 6.9-7.8,
    temperature 22°C, and dissolved oxygen 7.7-8.6 mg/litre.  These values
    were slightly different in the different tests, depending on the
    quantity of organic matter.  At the termination of the 14-day sediment
    studies, midge survival in all TBBPA-treated sediments ranged from 44
    to 96% and was statistically comparable to the survival of controls. 
    Organism growth (determined by the measurement of grouped body
    weights) at test termination was not significantly different for any
    of the 3 different levels of organic carbon.  The high organic carbon
    (HOC), medium organic carbon (MOC), and low organic carbon (LOC)
    contents of the sediments were 68, 27, and 2.5 g/kg, respectively. 
    The sediments were physically characterized by a high sand content of
    920-940 g/kg, a silt content of 10-60 g/kg, and a clay content of
    20-60 g/kg and were slightly acidic (pH 5.4-5.5). The mean, measured
    concentrations of TBBPA in HOC, MOC, and LOC, were 0.0044-0.046,
    0.0075-0.045, and 0.0078-0.046 mg/litre, respectively.  The highest
    no-effect level was established at an interstitial water concentration
    of 0.046 mg TBBPA/litre, which was the highest concentration attained
    in the HOC treatment.  The TBBPA concentration in the HOC sediment was
    340 mg/kg. The no-effect level in the interstitial waters of MOC and
    LOC treatments were 0.045 and 0.046 mg TBBPA/litre.  The TBBPA
    concentrations of the sediments in MOC and LOC treatments were 240 and
    230 mg/kg.  Bioconcentration factors in the midge ranged from 240 to
    510 in the HOC sediments, 490 to 1100 in the MOC sediments, and 650 to
    3200 in the LOC sediments.  A high organic content in the sediment
    reduced accumulation.  No adverse biological effects resulted from the
    increased TBBPA body burden.  No relationship was observed between the
    sediment concentration of TBBPA and midge body burden (section 4.2.4)
    (Breteler, 1989).

    9.2  Field observations

         No data are available on this subject.

    9.3  Miscellaneous

         Kawamura et al. (1986) designed a study to investigate the
    effects of TBBPA on the aerobic metabolism of the bisphenolic
    derivative-sensitive protozoon,  Giardia lamblia.  In this study,
    trophozoites of  G. lamblia were grown in a medium for 72 h at
    35.5°C.  The parasites, which were harvested and washed, and, finally,
    suspended in a buffered sucrose in a final protein concentration of
    5-8 mg/ml, were disrupted by homogenization for 10 min.  Inhibition of
    endogenous respiration, and the activities of NADH- and NADPH oxidase
    in  Giardia by TBBPA were measured.  The concentrations of TBBPA
    needed for 50% inhibition of endogenous respiration, NADH oxidase, and
    NADPH oxidase, were 0.30, 0.15, and 0.15 mmol/litre, respectively.

    TETRABROMOBISPHENOL A DERIVATIVES

         Five derivatives of TBBPA were identified as being in commercial
    use as flame retardants.  These are: tetrabromobisphenol A
    dibromopropylether, tetrabromobisphenol A bis(allylether),
    tetrabromobisphenol A bis(2-hydroxyethyl ether), tetrabromobisphenol A
    carbonate oligomers, and tetrabromobisphenol A brominated epoxy
    oligomer.  In addition, the dimethylated derivative of TBBPA has been
    identified in a few environmental samples.  This dimethylated-TBBPA
    derivative is suspected of being an environmental metabolite of TBBPA.

         Few data are available on these TBBPA derivatives.  The available
    data are summarized in Appendix A.  No evaluations or recommendations
    were made because of the lack of data.  The five TBBPA-derived flame
    retardants are not extensively used (approximately 25% the global
    volume of TBBPA).  They are believed to be used in specialized (or
    niche) applications. 

    A.  TETRABROMOBISPHENOL A DIMETHYLETHER

    A.1  SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS

         There is no data base on which to make an evaluation of
    tetrabromobisphenol A dimethylether, or to support its use
    commercially.

         Tetrabromobisphenol A dimethylether cannot be evaluated unless
    adequate data become available on physical and chemical properties,
    production and use, environmental transport, distribution, and
    transformation, environmental levels and human exposure, kinetics and
    metabolism in animals and humans, effects on laboratory mammals,
    humans, and  in vitro test systems, and effects on other organisms in
    the laboratory and field.

    A.2  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
         METHODS

    A.2.1  Identity

    Chemical formula         C17H16Br4O2

    Chemical structure       CHEMICAL STRUCTURE 2










    CAS registry
     number                  37853-61-5

    Synonyms                 1,1'-(1-methylethylidene) bis(3,5-dibromo-
                             4-methoxy) benzene; tetrabromobiphenyl
                             A-bis(methylether); tetrabromobisphenyl
                             A methylether

    Relative molecular
     mass                    571.9

    Vapour pressure
     at 25°C                 2 × 10-7 Torr (Watanabe & Tatsukawa, 1990)

    Log Pow                  6.4-7.6 (Watanabe & Tatsukawa, 1990;
                             Sellström et al., 1994).

    A.3  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         As far as is known, the dimethylether of TBBPA is not used
    commercially as a flame retardant (McAllister, 1994, personal
    communication).

         No data are available on environmental transport, distribution,
    and transformation.

    A.4  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         No data are available on the following subjects:

    *    Kinetics and metabolism in laboratory animals and humans

    *    Effects on laboratory mammals and  in vitro test systems

    *    Effects on humans

    *    Effects on other organisms in the laboratory and field

    A.4.1  Sediment

         Me2-TBBPA has been found in 5 out of 19 sediment samples from
    Japan at levels of 0.6-1.8 µg/kg dry weight (Watanabe & Tatsukawa,
    1990).  The dimethylated derivative was also found in Swedish
    sediments close to an industry using TBBPA.  The level upstream from
    the factory was 36 µg/kg, and that downstream, 430 µg/kg ign.loss
    (Sellström et al., 1990).

    A.4.2  Fish and shellfish

         In 2 out of the 19 investigated fish and shellfish samples from
    Japan, Me2-TBBPA was detected at levels of 0.8 and 4.6 µg/kg wet
    weight (Watanabe & Tatsukawa, 1990).

    B.  TETRABROMOBISPHENOL A DIBROMOPROPYLETHER

    B.1  SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS

         There is no data base on which to make an evaluation of
    tetrabromobisphenol A dibromopropylether, or to support its use
    commercially.

         From the available data it can be concluded that the acute and
    short-term toxicities of tetrabromobisphenol A dibromopropylether are
    low.  The substance was tested for mutagenicity and was a direct
    mutagen in  Salmonella typhimurium strains TA100 and TA1535. 
    However, the results of an unscheduled DNA synthesis assay and an
     in vitro Sister Chromatid Exchange test were negative.

         This substance cannot be evaluated until adequate data become
    available on physical and chemical properties, production and use,
    environmental transport, distribution and transformation,
    environmental levels and human exposure, kinetics and metabolism in
    animals and humans, effects on laboratory mammals and humans, and
    effects on other organisms in the laboratory and field.

    B.2  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
         METHODS

    B.2.1  Identity

    Chemical formula         C21H20Br8O2

    Chemical structure       CHEMICAL STRUCTURE 3
















    CAS registry
     number                  21850-44-2

    Synonyms                 1,1'-(1-methylethylidene) bis (3,5-dibromo-
                             4-(2,3-dibromopropoxy)-benzene; Bis(2,3-
                             dibromopropoxy)-tetrabromobisphenol A;
                             propane 2,2'-bis[3,5-dibromo-4-(2,3-
                             dibromopropoxy)phenyl]; tetrabromobis
                             phenol A dibromopropyl ether; 2,2'-bis[4-
                             (2,3-dibromopropoxy)-3,5-dibromophenyl]-
                             propane; bis(2,3-dibromo-propylether) of
                             tetrabromobisphenol A; Dibromopropydian

    Trade names              Bromcal 66.8; Fire guard 3100; PE-68

    B.2.2  Physical and chemical properties

         Tetrabromobisphenol A dibromopropylether is a crystalline or
    powdered white/off-white solid, with a slight odour.  Decomposition
    takes place at temperatures > 270°C.  The bromine content is 68%
    (Arias, 1992).  Other properties from Kopp (1990) are listed below.

    Relative molecular
     mass                    943.9

    Melting point            90-100°C (95°C)

    Specific gravity         0.7-0.9 g/cm3

    Solubility               1 g/litre water at 25°Ca

    B.3  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    B.3.1  Uses

         This substance is used as an additive flame retardant in
    polyolefins (Arias, 1992).

    B.4  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

         Biodegradation tests have shown a negative response, and
    accumulation in carp was judged to be very small (Great Lakes Chemical
    Corporation, 1987, summary report).

                 

    a  This solubility seems to be too high.

         No data are available on the following subjects:

    *    Environmental levels and human exposure

    *    Kinetics and metabolism in laboratory animals and humans

    *    Effects on humans

    *    Effects on other organisms in the laboratory and field

    B.5  EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS

         No data are available on:

    *    Long-term exposure

    *    Skin and eye irritation; sensitization

    *    Reproductive toxicity, embryotoxicity, teratogenicity, and  
         carcinogenicity

    B.5.1  Single exposure

         The acute LD50 for mice was > 20 g/kg when given in feed and
    observed for 14 days.  The acute dermal LD50 for mice was > 20 g/kg
    when applied to closely clipped intact skin for 24 h and then observed
    for 14 days (Great Lakes Chemical Corporation, 1987, summary report).

    B.5.2  Short-term exposures

         Mice were administered levels of 200 or 2000 mg/kg per day in
    their diet for 90 days.  At the end of the study, no deaths had
    occurred at either level.  No abnormal symptoms were observed in the
    gross pathological examination (Great Lakes Chemical Corporation,
    1987, summary report).

    B.5.3  Mutagenicity and related end-points

    B.5.3.1  Mutation

         Three mutagenicity studies were carried out on  Salmonella
     typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100 with,
    and without, S9 fraction of livers of male Sprague-Dawley rats induced
    by Aroclor 1254.  Eight dose levels of PE-68 (samples coded as
    785-104A, 785-104B, and 785-104C) were used to test the mutagenicity,
    ranging from 1.00 µg to 10 000 µg/plate.  DMSO was used as solvent. 
    Samples 785-104A and 785-104C exhibited mutagenic activity with
    strains TA1535 and TA100 in the activation assay and with strains
    TA1535, TA100, and TA98 in the non-activation assay. Sample 785-104B
    exhibited mutagenic activity in the non-activation assay with TA1535

    and TA100.  These tests indicate that PE-68 is a direct-acting mutagen
    and that a rat liver S9 mix converts the test material to a less
    mutagenic form (Brusick, 1982).

    B.5.3.2  Unscheduled DNA synthesis assay

         PE-68 was tested in a rat (Sprague-Dawley) unscheduled DNA
    Synthesis Assay in duplicate doses of 10, 50, 100, 500, and
    1000 µg/ml.  The high dose was selected on the basis of the solubility
    of PE-68 in DMSO.  No significant increase in the mean nuclear grain
    count was observed at any dose level compared with the solvent
    control.  Positive medium and solvent controls confirmed the
    sensitivity of the system (Cavagnaro & Sernau, 1984).

    B.5.3.3  In vitro sister chromatid exchange in Chinese hamster ovary
             cells

         Chinese hamster ovary cells (CHO, K-1, number CCL61) were exposed
    to 5 concentrations of PE-68 in DMSO (5, 17, 50, 170, and 500 µg/ml)
    for 2 h in the presence, or absence, of metabolic activation followed
    by a 24-h expression period in comparison with solvent and positive
    controls.  At dosing, it was noted that the culture medium became
    cloudy at 170 µg/ml and that the compound precipitated at 500 µg/ml. 
    No statistically significant increases in the number of exchanges per
    chromosome or the number of exchanges per cell were seen at any of the
    levels tested, either with, or without, metabolic activation.  PE-68
    is considered to be negative in this system (Cavagnaro & Cortina,
    1984).

    C.  TETRABROMOBISPHENOL A BIS(ALLYLETHER)

    C.1.  SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS

         There is no data base on which to make an evaluation of
    tetrabromobisphenol A bis(allylether), or to support its use
    commercially.

         From the available data it can be concluded that the acute oral
    and dermal toxicities of this compound are low.  Skin and eye
    irritation studies on rabbits showed that the substance was a mild
    irritant for the eyes and skin.

         This substance cannot be evaluated unless adequate data on
    physical and chemical properties, production and use, environmental
    transport, distribution, and transformation, environmental levels and
    human exposure, kinetics and metabolism in animals and humans, effects
    on laboratory mammals, humans, and  in vitro test systems, and
    effects on other organisms in the laboratory and field, become
    available.

    C.2  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
         METHODS

    C.2.1  Identity

    Chemical formula         C21H20Br4O2

    Chemical structure       CHEMICAL STRUCTURE 4

    CAS registry
     number                  25327-89-3

    Trade names              BE-51

    C.2.2  Physical and chemical properties

         BE-51 is a crystalline white solid.  The substance contains 51%
    bromine (Arias, 1992).  By overheating, decomposition will take place
    with release of hydrogen bromide.

    Relative molecular
     mass                    655.9

    Melting point            115-120°C

    Specific gravity         1.8

    Solubility               < 1 g/litre water at 25°C

    C.2.3  Analytical methods

         No data on this subject are available.

    C.3  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    C.3.1  Uses

         It is used as a reactive flame retardant in polystyrene foams
    (Arias, 1992).

         No data are available on the following subjects:

    *    Environmental transport, distribution, and transformation

    *    Environmental levels and human exposure

    *    Kinetics and metabolism in laboratory animals and humans

    *    Effects on humans

    *    Effects on other organisms in the laboratory and field

    C.4  EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS

         No data are available on the following subjects:

    *    Short-term exposures

    *    Long-term exposure

    *    Reproductive toxicity, embryotoxicity, teratogenicity, and  
         carcinogenicity

    C.4.1  Single exposure

         Sprague-Dawley rats (groups of 5 of each sex) (212-268 g) were
    administered (by gavage) a single dose of 5 g BE-51/kg body weight in
    corn oil.  The observation time was 14 days.  None of the rats died
    during the study and no signs of systemic toxicity were observed.  The
    LD50 is > 5 g/kg body weight (Abbott et al., 1981).

         A single dose of 2 g BE-51/kg body weight was applied to the
    clipped, abraded back skin of 5 male and 5 female young New Zealand
    albino rabbits (2.05-2.45 kg).  The test site was covered with an
    occlusive wrap for 24 h.  At the end of this period, the covering was
    removed and the residual test material wiped off.  The observation
    time was 14 days.  No animals died or exhibited signs of systemic
    toxicity, and body weight gain was normal.  Slight to moderate
    erythema and oedema were observed.  The skin reactions decreased in
    severity and area with time.  No gross pathological findings were
    observed during necropsy.  The dermal LD50 is > 2 g/kg body weight
    (Abbott et al., 1981).

    C.4.2  Skin and eye irritation; sensitization

         Young New Zealand albino rabbits (3 male and 3 female)
    (2.25-2.55 kg) were clipped on 4 sites on the back.  Two test sites
    were abraded and 2 were left intact.  A sample of 0.5 g BE-51,
    slightly moistened with physiological saline, was applied to each site
    and occluded for 24 h.  At the end of this period, the covering was
    removed and the residual test material wiped off.  The observation
    time was 4 days.  Body weight gain was normal.  No signs of systemic
    toxicity were observed and no deaths occurred.  The primary skin
    irritation index was calculated to be 1.0 and BE-51 was classified as
    mildly irritating using the Draize criteria for evaluation (Abbott et
    al., 1981).

         The eyes of 4 male, and 5 female, young New Zealand albino
    rabbits (1.95-2.55 kg) were examined after the instillation of 0.1 g
    BE-51 in the conjunctival sac of one eye.  The other eye was untreated
    and served as control.  The treated eyes of one male and two female
    rabbits were flushed after 30 seconds with distilled water for 1 min. 
    The eyes of the remaining rabbits were not flushed.  Eye examinations
    for irritation were made at 24, 48, and 72 h, and, 4 and 7 days
    following application. No deaths occurred, body weight gain was
    normal, and no systemic toxicity symptoms were observed.  Various
    degrees of swelling and redness were observed at the conjunctiva
    lasting for 4 days (not rinsed) and 48 h (rinsed).  An irregular
    corneal surface (stippling) was observed in 6/9 of the rabbits.  No
    signs of corneal damage were noted upon fluorescein examinations.  The
    primary irritation index was determined to be 4.0 for unrinsed eyes
    and 1.33 for rinsed eyes.  On the basis of these data, the substance
    is classified as mildly irritating for unrinsed eyes and minimally
    irritating for rinsed eyes (Abbott et al., 1981).

    C.4.3  Mutagenicity and related end-points

         A mutagenicity study was conducted with  Salmonella and
     Saccharomyces indicator organisms, with, and without, metabolic
    activation with liver S9 fraction from Aroclor-induced rats.  The dose
    levels of BE-5I ranged from 0.1 to 500 µg per plate.  No mutagenic
    activity was found in this test (Brusick, 1977).

    D.  TETRABROMOBISPHENOL A BIS(2-HYDROXYETHYL ETHER)

    D.1  SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS

         The data base is inadequate for an evaluation of
    tetrabromobisphenol A bis(2-hydroxyethyl ether), or to support its use
    commercially.

         From the available data, there is some indication that this
    substance may occur in the environment.  The acute toxicity was low
    after oral and dermal administration in rats and rabbits,

    respectively.  The acute inhalation toxicity (1-h exposure) in rats
    seemed to be moderate.  A short-term toxicity study on rats showed no
    effects with 1000 mg/kg diet, but a significant increase in total
    bromine content in organs was observed.  The substance was found not
    to irritate the skin and eyes of rabbits.  The results of a
    mutagenicity study with five strains of  Salmonella typhimurium,
    with, and without, metabolic activation, were negative.

         The substance cannot be evaluated unless additional data on
    physical and chemical properties, production and use, environmental
    transport, distribution, and transformation, environmental levels and
    human exposure, kinetics and metabolism in animals and humans, effects
    on laboratory mammals, humans, and  in vitro test systems, and
    effects on other organisms in the laboratory and field, become
    available.  An  in vitro cytogenetic study is also required.

    D.2  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
         METHODS

    D.2.1  Identity

    Chemical formula         C19H20Br4O4

    Chemical structure       CHEMICAL STRUCTURE 5

    CAS registry
     number                  4162-45-2

    Trade names              BA-50P; BA-50, Firegard 3600

    D.2.2  Physical and chemical properties

         The substance is a crystalline, white coloured, slightly chunky
    powder.  It contains 51% bromine (Arias, 1992).  BA-50P may release
    hydrogen bromide and/or bromine in fires fuelled by other products.

    Melting point            approximately 112°C (115°C)

    Specific gravity         approximately 1.80

    D.3  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         This substance is used as an additive flame retardant in
    engineering polymers and coatings (Arias, 1992).

    D.4  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

         Carp were exposed to TBBPA bis(2-hydroxyethyl ether) at
    concentrations of 0.25 or 0.025 mg/litre, for 8 weeks. 
    Bioaccumulation was 10.0-35.5 and 14.8-53.0, respectively (Chemicals
    Inspection and Testing Institute, 1992).

    D.5  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    D.5.1  Environmental levels

    D.5.1.1  Air

         No data are available.

    D.5.1.2  Water

         In 1986, an environmental survey was conducted concerning BA-50P
    in water at different locations in Japan.  BA-50P was detected in
    2 out of 30 samples at concentrations ranging from 20 to 40 µg/litre
    (limit of determination, 20 µg/litre) (Environment Agency Japan,
    1989).

    D.5.1.3  Soil

         In 1986, an environmental survey was conducted concerning BA-50P
    in bottom sediment at different locations in Japan.  BA-50P was not
    detected in 30 samples (limit of determination, 20 µg/kg dry weight)
    (Environment Agency Japan, 1989).

         No data are available on the following subjects:

    *    Kinetics and metabolism in laboratory animals and humans

    *    Effects on humans

    *    Effects on other organisms in the laboratory and field

    D.6  EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS

         No data are available on the following subjects:

    *    Long-term exposure

    *    Reproductive toxicity, embryotoxicity, teratogenicity, and  
         carcinogenicity

    D.6.1  Single exposure

         Groups of five male Spartan rats (210-235 g) were administered
    (by gavage) 50, 500, or 5000 mg TBBPA bis(2-hydroxyethyl ether)/kg
    body weight.  The compound was administered in corn oil at
    concentrations permitting a total dose of 10 ml/kg at all dose levels. 
    The observation time was 14 days.  None of the rats receiving 50 and
    500 mg/kg died and they exhibited normal body weight gain.  In the
    5000 mg/kg group, 2 out of 5 rats died during the 14 days, and the
    three remaining rats showed decreased body weight gain.  The acute
    oral LD50 was > 5.0 g/kg body weight (Goldenthal & Dean, 1974).

         TBBPA bis(2-hydroxyethyl ether) was applied to the closely
    clipped intact skin of two male and two female New Zealand albino
    rabbits (2339-2937 g) each at dose levels of 200 or 2000 mg/kg body
    weight.  The application site was occluded for 24 h.  The bandages
    were removed and the backs were washed with tepid tap water.  The
    observation time was 14 days.  No rabbits died during the study.  At
    200 and 2000 mg/kg, 3 out of 4 rabbits gained weight while 1 out of
    4 lost weight in each group.  The acute dermal LD50 for rabbits is
    > 2 g/kg body weight (Goldenthal & Dean, 1974).

         Two groups of 5 male and 5 female Spartan rats (210-236 g) were
    exposed for 1 h to a dynamic atmosphere containing TBBPA
    bis(2-hydroxyethyl ether) dust at calculated concentrations of 2 or
    12.5 mg/litre of air.  The observation time was 14 days.  Nine out of
    10 rats at the 2 mg/litre dose survived and appeared normal during the
    first 8 days; one rat showed slight dyspnoea on days 4 and 5.  From
    days 9-14, one or two rats exhibited ocular discharge or drying of the
    corneal surface for a few days.  The rats showed normal body weight
    gain.  All rats exposed to 12.5 mg/litre survived and exhibited normal
    growth.  During exposure, rats showed a slight increase in motor
    activity for the first 10 min of exposure and eye squint.  At 24 h and
    up to day 8 of the 14-day observation period, all rats appeared
    normal, with the exception of one rat that exhibited marked and slight
    dyspnoea on days 4 and 5, respectively.  From day 9 onwards, one or
    two rats exhibited drying of the corneal surface accompanied by eye
    squint.  The LC50 for inhalation of TBBPA bis(2-hydroxyethyl ether)
    dust is > 12.5 mg/litre (Goldenthal & Dean, 1974).

    D.6.2  Short-term exposures

         Charles River CD rats (males 296-392 g; females 205-257 g) were
    fed dietary levels of 0, 100, or 1000 mg TBBPA bis(2-hydroxyethyl
    ether)/kg for 28 days.  There were 10 male and 10 female rats in each
    group.  Feed consumption and body weight gain were recorded.  At the
    end of the study, all rats were killed.  Besides gross pathological
    examination, the liver, kidneys, and thyroid were examined
    microscopically.  Liver and fat tissues were pooled according to sex
    and dose groups for bromine determination.  None of the rats died, and
    no changes were noted in the behaviour or appearance of any of the
    rats during the study.  Feed consumption and body weight gain were
    normal.  A slight increase in the bromine contents (5.0-7.3 mg/kg) of
    the liver was seen, but not in the fat tissue of the rats receiving
    100 mg/kg.  At the 1000 mg/kg level, a definite increase in total
    bromine content was seen in both the liver (18.3-48.8 mg/kg) and fat
    (4.4-22.1 mg/kg) tissue.  No compound-related changes in organ
    weights, gross pathological lesions, or histopathological changes were
    observed in the liver, kidneys, or thyroid, in any of the rats
    (Goldenthal & Geil, 1974).

    D.6.3  Skin and eye irritation; sensitization

         Three male and three female New Zealand albino rabbits
    (2682-2998 g) had 500 mg TBBPA bis(2-hydroxyethyl ether) applied to
    the closely clipped intact skin (3 rabbits) or to the closely clipped
    abraded skin (other three rabbits).  The application site was occluded
    for 24 h, after which the rabbits' skin was washed and examined for
    skin irritation.  The examinations were repeated at 72 h.  At 24 and
    72 h, 1/3 rabbits in the intact group exhibited very slight erythema
    or very slight oedema.  No erythema or oedema was observed in the
    rabbits with the abraded skin.  The calculated primary irritation
    score was 0.2 and indicated that the substance was not a primary skin
    irritant (Goldenthal & Dean, 1974).

         Single applications of 100 mg TBBPA bis(2-hydroxyethyl ether)
    were made into the conjunctival sac of one eye of three male and three
    female New Zealand albino rabbits (2443-2670 g).  Examinations were
    done at 24, 48, and 72 h and at 7 days.  At 72 days, fluorescein and
    UVR were used to detect corneal damage.  No corneal damage, iridal
    irritation, or conjunctival discharge was noted.  Very slight to
    slight redness and very slight chemosis of the conjunctivae were noted
    in some of the animals at 24, 48, and 72 h, with decreasing frequency
    until all rabbits appeared normal at 7 days.  These results indicate
    that the substance is not an eye irritant (Goldenthal, & Dean, 1974).

    D.6.4  Mutagenicity and related end-points

         TBBPA bis(2-hydroxyethyl ether) was examined for mutagenic
    activity in the microbial assays using  Salmonella typhimurium
    TA1535, TA1537, TA1538, TA98, and TA100 in the presence, or absence,

    of liver microsomal enzyme preparations from Aroclor 1254-induced
    rats.  The concentrations tested were 0, 0.5, 1, 10, 100, 500, and
    1000 µg/plate, in comparison with positive control substances.  The
    results indicated that the substance was not mutagenic under these
    test conditions (Jagannath & Brusick, 1979).

    E.  TETRABROMOBISPHENOL A BROMINATED EPOXY OLIGOMER

    E.1  SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS

         The data base is inadequate for an evaluation of tetrabromo-
    bisphenol A brominated epoxy oligomer, and to support its use
    commercially.

         Some, but insufficient, data on the physical and chemical
    properties and production and use of tetrabromobisphenol A brominated
    epoxy oligomer are available.  The quantities of PBDD and PBDF
    produced when resins containing these epoxy oligomers were pyrolised
    were much lower than those produced when TBBPA was pyrolysed.

         These substances cannot be evaluated unless adequate data
    on their physical and chemical properties, production and use,
    environmental transport, distribution, and transformation,
    environmental levels and human exposure, kinetics and metabolism in
    laboratory animals and humans, effects on laboratory mammals, humans,
    and  in vitro test systems, and effects on other organisms in the
    laboratory and field, become available.

         As the use of these compounds seems to be increasing, at least
    in Japan, it is essential that further studies are performed.

    E.2  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
         METHODS

    E.2.1  Identity

         There are two chemically different types of brominated epoxy
    oligomers.  One has two epoxy groups at the end of the molecule, which
    is quite similar to epoxy resins used for printed circuit boards
    (EP-type).  The other has no reactive groups.  This is TBBPA epoxy
    end-capped with tribromophenol (EC-type) (Satoh & Sugie, 1993).

    Chemical structure

    EP type (Epoxy terminated):

    CHEMICAL STRUCTURE 6

    EC type (tribromophenol end-capped):

    CHEMICAL STRUCTURE 7

    E.2.2  Physical and chemical properties

                                  EP Type             EC Type

    Relative molecular
     mass                         1.300-40.000        1.400-3.000

    Appearance                    light yellow        light yellow
                                   powder              powder

    Specific gravity              1.8                 1.9

    Bromine contents (%)          50-52               59-55

    Softening point (°C)          103-> 200          99-140

    From: Satoh & Sugie (1993).

    E.2.3  Analytical methods

         No data are available.

    E.3  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    E.3.1  Natural occurrence

         Brominated epoxy oligomers have not been reported to occur
    naturally.

    E.3.2  Anthropogenic sources

    E.3.2.1  Production levels and processes

         Brominated epoxy oligomer flame retardants were first introduced
    on the Japanese market in 1987, with a demand of approximately
    3000 tonnes in 1991.  Demand requirements still show a rapid growth in
    Japan as well as in the USA.

         The products are especially characterized by a higher melt flow
    rate without blooming, and a better light stability than existing
    flame retardants, such as polybrominated diphenylethers and others
    (Satoh & Sugie, 1993).

    E.3.2.2  Uses

         Brominated epoxy oligomers are reactive flame retardants.  They
    have been applied in housings for business machinery and electrical/
    electronics parts by injection moulding from flame retardant compounds
    based upon HIPS, ABS, ABS/PC, or PBT alloys, PBT, and thermosetting
    resins.  A new application is for use in large-size TV sets, moulded
    from HIPS.

         The concentrations of the flame retardant in ABS are 21% of the
    EP-type and 19% of the EC-type. Brominated epoxy oligomers are used in
    combination with 5% of Sb2O3 (Satoh & Sugie, 1993). 

    E.4  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

    E.4.1  Pyrolysis of polymers containing brominated epoxy oligomers

         ABS containing the EP-type and EC-type brominated epoxy oligomers
    and Sb2O3 were heated at 600°C.  Gas and ash were collected and
    analysed for the presence of PBDF and PBDD.  In this study, TBBPA was
    also tested for comparison.  TBBPA produced 0.9 µg 2,3,7,8-PBDD/kg
    including PeBDD and HxBDD, and 22 µg 2,3,7,8-PBDF/kg.  The EP-type
    gave < 0.5 µg/kg (sum of TeBDD, PeBDD, and HxBDD) and the EC-type
    < 4 µg/kg.  The values for the sum of TeBDF, PeBDF, and HxBDF were
    0.5 and < 4 µg/kg, respectively (Satoh & Sugie, 1993).

         No data are available on the following subjects:

    *    Environmental levels and human exposure

    *    Kinetics and metabolism in laboratory animals and humans

    *    Effects on laboratory mammals and  in vitro test systems

    *    Effects on humans

    *    Effects on other organisms in the laboratory and field

    F.  TETRABROMOBISPHENOL A CARBONATE OLIGOMERS

    F.1  SUMMARY AND EVALUATION; CONCLUSIONS AND RECOMMENDATIONS

         There is no data base on which to make an evaluation of
    tetrabromobisphenol A carbonate oligomer, or to support its use
    commercially.

         The results of mutagenicity studies with five strains of
     Salmonella typhimurium, with, and without, metabolic activation,
    were negative for both substances.

         These substances cannot be evaluated unless adequate data on
    physical and chemical properties, production and use, environmental
    transport, distribution, and transformation, environmental levels and
    human exposure, kinetics and metabolism in animals and humans, effects
    on laboratory mammals, humans, and  in vitro test systems, and
    effects on other organisms in the laboratory and field, become
    available.   In vitro cytogenetic studies are also required.

    F.2  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

    F.2.1  Identity of BC-52

    Chemical formula         (C7H5O2) (C16H10Br4O3)x
                             x = 3-5

    Chemical structure

    CHEMICAL STRUCTURE 8

    CAS registry
     number                  94334-64-2

    F.2.1.1  Physical and chemical properties

         BC-52 is a white powder.  Its bromine content is 55%.  It may
    release hydrogen bromide and/or bromine in fires fuelled by other
    products.

         In BC-52, 6 ng/kg TeBDD was found.  No PBDF and no 2,3,7,8-
    substituted isomers were detected (limits of detection ranged from
    1 to 400 ng/kg for DiBDF/DiBDD to OBDF/OBDD) (Brenner & Knies, 1993).

    Melting point            210-230°C

    Solubility in water      < 0.1% in water at 25°C

    From: Kopp (1990); Arias (1992).

    F.2.2  Identity of BC-58

    Chemical formula         (C7H2Br3O3) (C16H10Br4O3)n (C6H2Br3)

    Chemical structure
 
    CHEMICAL STRUCTURE 9

    CAS registry
     number                  71342-77-3

    F.2.2.1  Physical and chemical properties

         BC-58 is a white powder. It may release hydrogen bromide and/or
    bromine in fires fuelled by other products.  The following properties
    are from Kopp (1990).

    Melting point            230-260°C

    Specific gravity         2.2

    Solubility in water      negligible

    F.3  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    F.3.1  Uses

         These oligomers are used as an additive flame retardant in
    engineering thermoplastics and ABS (Arias, 1992).

    F.4  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

    F.4.1  Transport and distribution

         No data are available on environmental transport and
    distribution.

    F.4.2  Transformation

    F.4.2.1  Pyrolysis

         In general, the pyrolysis of tetrabromobisphenol A oligomer in
    combination with antimony trioxide at temperatures of 200, 250, or
    600°C, over 30 min, resulted in only low levels (up to 15 mg/kg) of
    PBDF.  No PBDD was found (Fresenius Institute, 1990).

    F.4.2.2  Monitoring of PBDF/PBDD during extrusion blending and
             injection moulding

         Thies et al. (1990) reported investigations into the processing
    of a polymer containing polybutylene-terephthalate, 10% TBBPA -
    oligocarbonate, and 5% antimony trioxide.  PBDD/PBDF levels were
    determined in the polymer and the condensate after a 20-min treatment
    at 240°C in the BIS-apparatus.  Mono- and di-BDF were detected at 13
    and 10 µg/kg, respectively, but levels of other PBDD/PBDF were less
    than 2 µg/kg.

         Brenner & Knies (1993) analysed PBDF and PBDD: a) during the
    extrusion of PBT blended with BC-52 powder (BC-52; ca. 11%/Sb2O3
    ca. 4%), b) during the extrusion of BC-52 PBT-batch (ca. 50% BC-52),
    and, c) during injection moulding of the produced PBT/glass-fibre/
    BC-52/Sb2O3 resin.

         Air monitoring was performed at the workplace, and the exhaust
    air was measured at the extruder and injection heads in the granulator
    exhaust line.

         The results of the extruder experiment with BC-52 powder (PBDF
    concentrations in ng/m3) are shown in Table A.

         DiBDD, TrBDD, and TeBDD were found in concentrations of 0.94,
    0.07, and 0.08 ng/m3, respectively, at the extruder head, and,
    0.02 ng/m3 DiBDD in the granulator.  The levels of all other PBDDs
    were below the limit of detection.

         The results of the extruder experiment with PBT/BC-52 (use of
    BC-52 batch) are shown in Table B.

    Table A.  PBDF concentrations in ng/m3a
                                                                        
                   DiBDF     TrBDF     TeBDF    PeBDF    HxBDF    HpBDF
                                                                        

    Workplace      0.34      0.11      0.05     0.07     0.05     n.d.b

    Extruder head  0.42      0.48      0.24     0.04     0.15     n.d.b

    Granulator     0.23      0.29      0.17     0.02     n.d.b    n.d.b
                                                                        

    a  From: Brenner & Knies (1993).
    b  n.d. = not detected (below limit of detection).


    Table B.  PBDF concentrations in ng/m3a
                                                                        
                   DiBDF     TrBDF     TeBDF    PeBDF    HxBDF    HpBDF
                                                                        

    Workplace      0.14      0.35      0.08     0.05     0.02     n.d.b

    Extruder head  0.16      0.31      0.06     0.333    0.01     n.d.b

    Granulator     0.2       0.42      0.08     0.07     0.24     n.d.b
                                                                        

    a  From: Brenner & Knies (1993).
    b  n.d. = not detected (below limit of detection).


         DiBDD concentrations of 0.001, 0.007, and 0.003 ng/m3 were
    detected at monitoring points at the workplace, extruder head, and
    granulator.

         The results of the injection moulding experiment performed with
    PBT/glass fibre/BC-52/Sb2O3 granulate are shown in Table C.

         PBDD were also found including: DiBDD at < 1 pg/m3 and OBDD at
    < 232 pg/m3 (limits of detection).  No 2,3,7,8-TeBDD could be
    detected (limit of detection 0.001-0.058 ng/m3) (Brenner & Knies,
    1993).

    F.4.2.3  PBDD/PBDF levels in polymer samples using BC52-powder,
             BC52-batch, and the moulded test articles produced from these

         Concentrations of PBDF in extruder granulate (PBT-granulate)
    using BC52 powder, and the moulded test articles produced from that,
    are listed in Table D.

    Table C.  PBDF concentrations in ng/m3a
                                                                        

                    DiBDF    TrBDF     TeBDF     PeBDF    HxBDF   HpBDF
                                                                        

    Workplace       n.d.b    n.d.b     0.029    0.187    0.262    n.d.b

    Injection head  0.004    0.012     0.014    0.013    0.039    n.d.b

    Storage         0.004    n.d.b     0.002    n.d.b    n.d.b    n.d.b
                                                                        

    a  From: Brenner & Knies (1993).
    b  n.d. = not detected (below limit of detection).


    Table D.  PBDF concentrations in µg/kga
                                                                        

                     DiBDF    TrBDF    TeBDF    PeBDF    HxBDF   HpBDF
                                                                        

    PBT granulate    n.d.b    n.d.b     n.d.b   n.d.b   0.4-0.8  0.6-3.5
    (three samples)

    Test article A   0.07     0.2      0.2      n.d.b   2.2      3.8

    Test article B   0.29     0.31     0.17     0.06    1.5      1.9
                                                                        

    a  From: Brenner & Knies (1993).
    b  n.d. = not detected.


         Finally, PBDF was determined in the BC-52/PBT batch and the
    product produced (PBT-granulate).  DiBDF was found in the two batch
    samples at concentrations of 1.0 and 1.4 µg/kg and in the granulate at
    0.6 µg/kg.  No other PBDF were found (Brenner & Knies, 1993).

    F.5  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         See section F.4.2.2 for monitoring at the workplace.

    F.6  EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS

    F.6.1  Single exposure

         The oral LD50 for BC-52 and BC-58 in the rat is > 5 g/kg, and,
    the dermal LD50 for the rabbit > 2.0 g/kg body weight (Kopp, 1990).

    F.6.2  Skin and eye irritation; sensitization

         BC-52 and BC-58 are not primary skin or eye irritants (Kopp,
    1990).

    F.6.3  Mutagenicity and related end-points

         Both substances were tested in 5 strains of  Salmonella
     typhimurium at doses ranging from 100 to 10 000 µg/plate, in the
    presence, and absence, of metabolic activation. Both gave negative
    results (Great Lakes 1983a,b).

         No data are available on the following subjects:

    *    Short-term exposures

    *    Long-term exposure

    *    Reproductive toxicity, embryotoxicity, teratogenicity, and  
         carcinogenicity

    *    Kinetics and metabolism in laboratory animals and humans

    *    Effects on humans

    *    Effects on other organisms in the laboratory and field

    REFERENCES

    Abbott L, Altringer L, Kingery AF, & Mayhew DA (1981) Acute dermal
    LD50 toxicity study in albino rabbits, acute eye irritation study in
    albino rabbits, acute oral LD50 toxicity study in albino rats,
    primary skin irritation study in albino rabbits with BE-51.
    Cincinnati, Ohio, Wil Research Laboratories, Inc. (Unpublished report
    No. WIL-81225 to Great Lakes Chemical Corporation, West Lafayette,
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Allard A-S, Remberger M, & Neilson AH (1987) Bacterial  O-methylation
    of halogen-substituted phenols. Appl Environ Microbiol,
    53(4): 839-845.

    Anon (1974) Markets for organo-bromo flame retardants depend on
    legislation. Eur Chem News, December 6: 48.

    Arias P (1992) Brominated diphenyloxides as flame retardant: Bromine
    based chemicals (Unpublished report to the Organisation for Economic
    Cooperation and Development, Paris).

    Bayer (1990) Chemical dossier on tetrabromobisphenol A. Leverkusen,
    Germany, Bayer AG (Unpublished report).

    Brady UE (1979) Pharmacokinetic study of tetrabromobisphenol A (BP-4A)
    in rats. Report from Athens, Georgie, University of Georgia (Report to
    Velsicol Chemical Corporation, Chicago, submitted to WHO by the
    Brominated Flame Retardant Industry Panel).

    Brenner KS & Knies H (1993) Workplace monitoring of PBDFs and PBDDs
    during extrusion production and injection molding of a
    polybutyleneterephthalte (PBTP)/glass fiber/tetrabromobisphenol A
    carbonate oligomer (BC52*)/Sb2O3-resin; Part II. Chemosphere,
    26(11): 1953-1963.

    Breteler RJ (1989) The subchronic toxicity of sediment-sorbed
    tetrabromobisphenol A  (Chironomus tentans) under flow-through
    conditions. Wareham, Massachusetts, Springborn Laboratories, Inc.
    (Report No. 90-08-3067 submitted to WHO by the Brominated Flame
    Retardant Industry Panel).

    Brusick D (1976) Mutagenicity evaluation of compound 279-117-2 (Final
    report). Report of Kensington, Maryland, Litton Bionetics, Inc.
    (Report to Great Lakes Chemical Corporation, West Lafayette, submitted
    to WHO by the Brominated Flame Retardant Industry Panel).

    Brusick D (1977) Mutagenicity evaluation of BE-51.  Kensington,
    Maryland, Litton Bionetics, Inc. (Report to Great Lake Chemical
    Corporation, West Lafayette, submitted to WHO by the Brominated Flame
    Retardant Industry Panel).

    Brusick D (1982) Mutagenicity evaluation of 785-104A, 785-104B and
    785-104C in the Ames  Salmonella/microsome plate test (Final report).
    Kensington, Maryland, Litton Bionetics, Inc. (Combined Reports Nos.
    LBI 7655, 7656, and 7657 to Great Lakes Chemical Corporation, West
    Lafayette, submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Calmbacher CW (1978a) The acute toxicity of FMBP4A
    (tetrabromobisphenol A) to the bluegill sunfish,  Lepomis macrochirus
    Rafinesque. Tarrytown, New York, Union Carbide Corporation,
    Environmental Services (Report to Velsicol Chemical Corporation,
    Chicago, submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Calmbacher CW (1978b) The acute toxicity of FMBP4A
    (tetrabromobisphenol A) to the rainbow trout,  Salmo gairdneri
    Richardson. Tarrytown, New York, Union Carbide Corporation,
    Environmental Services (Report to Velsicol Chemical Corporation,
    Chicago, submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Cavagnaro J & Cortina TA (1984)  In vitro sister chromatid exchange
    in Chinese hamster ovary cells with GLCC 785-104C (Final report).
    Vienna, Virginia, Hazleton Biotechnologies Corporation (Report to
    Great Lakes Chemical Corporation, West Lafayette, submitted to WHO by
    the Brominated Flame Retardant Industry Panel).

    Cavagnaro J & Sernau RC (1984) Unscheduled DNA synthesis rat
    hepatocyte assay, GLCC 785-104C. (Final report). Vienna, Virginia,
    Hazleton Biotechnologies Corporation (Report to Great Lakes Chemical
    Corporation, West Lafayette, submitted to WHO by the Brominated Flame
    Retardant Industry Panel).

    Chemicals Inspection & Testing Institute (1992) Biodegradation and
    bioaccumulation data of existing chemicals based on the CSCL, Japan.
    Tokyo, Japan Chemical Industry Ecology, Toxicology and Information
    Center, pp 4-14.

    Clausen E, Lahaniatis ES, Bahadir M, & Bieniek D (1987) [Determination
    of brominated dibenzofurans formed during the thermolysis of polymer
    with decabromodiphenyl ether as flame retardant.] Fresenius Z Anal
    Chem, 327: 297-300 (in German).

    Craig DK, Mitchum RK, Bauer MR, Yancey MF, Peters AC, & Joiner RL
    (1989) Determination of polybrominated dibenzo-p-dioxins and
    polybrominated dibenzofurans in CYCOLAC plastic resins and the fumes
    evolved during normal thermal processing (Final report). Columbus,
    Ohio, Batelle (Report No. 823-R-4289 to General Electric Company, Mt.
    Vernon, submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Dean WP, Jessup DC, Epstein WL, & Powell D (1978a) Tetrabromobisphenol
    A. Modified Draize multiple insult test in humans. Mattawan, Michigan,
    International Research and Development Corporation (Report to Velsicol
    Chemical Corporation, Chicago, submitted to WHO by the Brominated
    Flame Retardant Industry Panel).

    Dean WP, Jessup DC, Thompson G, Romig G, & Powell D (1978b) 
    Tetrabromobisphenol A. Dermal sensitization study in the albino
    guinea-pig. Mattawan, Michigan, International Research and Development
    Corporation (Report to Velsicol Chemical Corporation, Chicago,
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Dumler R, Thoma H, Lenoir D, & Hutzinger O (1989) PBDF and PBDD from
    the combustion of bromine containing flame retarded polymers: A
    survey. Chemosphere, 19(12): 2023-2031.

    Environment Agency Japan (1989) Chemicals in the environment. Report
    on environmental survey and wildlife monitoring of chemicals in F.Y.
    1986 and 1987. Tokyo, Environment Agency Japan, Department of
    Environmental Health, Office of Health Studies.

    Environment Agency Japan (1991) Chemicals in the environment.  Report
    on environmental survey and wildlife monitoring of chemicals in F.Y.
    1988 and 1989. Tokyo, Environment Agency Japan, Department of
    Environmental Health, Office of Health Studies.

    Ethyl Corporation (1992a) Material safety data sheet for emergencies.
    Baton Rouge, Louisiana, Ethyl Corporation, Chemicals Group (Report
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Ethyl Corporation (1992b) Saytex RB-100. Baton Rouge, Louisiana,
    Ethyl Corporation (Report submitted to WHO by the Brominated Flame
    Retardant Industry Panel).

    Fackler PH (1989a) Determination of the biodegradability of
    tetrabromobisphenol A in soil under aerobic conditions (Final report).
    Wareham, Massachusetts, Springborn Life Sciences, Inc. (Report No.
    88-11-2848 submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Fackler PH (1989b) Bioconcentration and elimination of 14C-residues
    by Eastern oysters  (Crassostrea virginica) exposed to
    tetrabromobisphenol A. Wareham, Massachusetts, Springborn Life
    Sciences, Inc. (Report No. 89-1-2918 submitted to WHO by the
    Brominated Flame Retardant Industry Panel).

    Fackler PH (1989c) Bioconcentration and elimination of 14C-residues
    by fathead minnows  (Pimephales promelas) exposed to
    tetrabromobisphenol A. Wareham, Massachusetts, Springborn Life
    Sciences, Inc. (Report No. 89-3-2952 submitted to WHO by the
    Brominated Flame Retardant Industry Panel).

    Fackler PH (1989d) Determination of the biodegradability of
    tetrabromobisphenol A in soil under anaerobic conditions. Wareham,
    Massachusetts, Springborn Life Sciences, Inc. (Report No. 88-11-2849
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Fackler PH (1989e) (Tetrabromobisphenol A) - Determination of the
    biodegradability in a sediment/soil microbial system. Wareham,
    Massachusetts, Springborn Life Sciences, Inc. (Report No. SLI
    89-8-3070 submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Fresenius Institute (1990) Summary results on pyrolysis of different
    types of ABS/Batelle report on contents and vapour-emission of PBDD
    resp. PBDF's. Taunusstein-Neuhof, Germany, Fresenius Institute (Report
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Giddings JM (1988) Toxicity of tetrabromobisphenol A to the
    freshwater green alga  Selenastrum capricornutum. Wareham,
    Massachusetts, Springborn Life Sciences, Inc. (Report No. 88-10-2828
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Goldenthal EI & Dean WP (1974) Bis(2-hydroxyethyl ether) of
    tetrabromobisphenol A. Acute toxicity studies in rats and rabbits.
    Mattawan, Michigan, International Research and Development Corporation
    (Report to Great Lakes Chemical Corporation, West Lafayette, submitted
    to WHO by the Brominated Flame Retardant Industry Panel).

    Goldenthal EI & Geil RG (1972) Tetrabromobisphenol A. Twenty-eight
    day toxicity study in rats. Mattawan, Michigan, International Research
    and Development Corporation (Report to Great Lakes Chemical
    Corporation, West Lafayette, submitted to WHO by the Brominated Flame
    Retardant Industry Panel).

    Goldenthal EI & Geil RG (1974) Bis(2-hydroxyethyl ether) of
    tetrabromobisphenol A; Decabromodiphenyl ether, 250-139-2;
    decabromodiphenyl ether, 143-78-6. Twenty-eight day toxicity study in
    rats. Mattawan, Michigan, International Research and Development
    Corporation (Report to Great Lakes Chemical Corporation, West
    Lafayette, submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Goldenthal EI, Geil RG, & Dean WP (1975) Tetrabromobisphenol A
    (micronized). Fourteen-days inhalation toxicity study in rats.
    Mattawan, Michigan, International Research and Development Corporation
    (Report to Great Lakes Chemical Corporation, West Lafayette, submitted
    to WHO by the Brominated Flame Retardant Industry Panel).

    Goldenthal EI, Jessup DC, & Rodwell DE (1978) Tetrabromobisphenol A
    (FMBP-4A). Pilot teratology study in rats. Mattawan, Michigan,
    International Research and Development Corporation (Report to Velsicol
    Chemical Corporation, Chicago, submitted to WHO by the Brominated
    Flame Retardant Industry Panel).

    Goldenthal EI, Jessup DC, Geil RG, Dean WP, & Ruecker FA (1979) 
    BP-4A. Three-week dermal toxicity study in rabbits. Mattawan,
    Michigan, International Research and Development Corporation (Report
    to Velsicol Chemical Corporation, Chicago, submitted to WHO by the
    Brominated Flame Retardant Industry Panel).

    Goodman LR, Cripe GM, Moody PH, & Halsell DG (1988) Acute toxicity of
    malathion, tetrabromobisphenol A and tributyltin chloride to Mysids,
     (Mysidopses bahia) of three ages. Bull Environ Contam Toxicol,
    41: 746-753.

    Great Lakes Chemical Corporation (1983a) Summaries of toxicity data.
    BC-52. West Lafayette, Indiana, Great Lakes Chemical Corporation
    (Unpublished report submitted to WHO by the Brominated Flame Retardant
    Industry Panel).

    Great Lakes Chemical Corporation (1983b) Summaries of toxicity data.
    BC-58. West Lafayette, Indiana, Great Lakes Chemical Corporation
    (Unpublished report submitted to WHO by the Brominated Flame Retardant
    Industry Panel).

    Great Lakes Chemical Corporation (1986) Summaries of toxicity data.
    Tetrabromobisphenol A. West Lafayette, Indiana, Great Lakes Chemical
    Corporation (Unpublished report submitted to WHO by the Brominated
    Flame Retardant Industry Panel).

    Great Lakes Chemical Corporation (1987) Summaries of toxicity data.
    PE-68, Bis(2,3-dibromopropyl ether) of tetrabromobisphenol A. West
    Lafayette, Indiana, Great Lakes Chemical Corporation (Unpublished
    report submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Gustafsson K & Wallen M (1988) Status report on tetrabromobisphenol A
    (CAS no. 79-94-7). Clearing house Sweden. Solna, Sweden, National
    Chemicals Inspectorate (Unpublished report).

    Hardy ML (1994) Summary; TBBPA toxicological studies sponsored by
    Ethyl Corporation. Baton Rouge, Louisiana, Ethyl Corporation (Report
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Inouye B, Katayama Y, Ishida T, Ogata M, & Utsumi K (1979) Effects of
    aromatic bromine compounds on the function of biological membranes.
    Toxicol Appl Pharmacol, 48: 467-477.

    Jagannath DR & Brusick DJ (1979) Mutagenicity evaluation of No.
    341-150 in the Ames  Salmonella/microsome plate test (Final report).
    Kensington, Maryland, Litton Bionetics, Inc. (Report No. LBI No. 20988
    to Great Lakes Chemical Corporation, West Lafayette, submitted to WHO
    by the Brominated Flame Retardant Industry Panel).

    Kawamura K, Takeuchi T, & Kobayashi S (1986) Inhibition of
    respiratory activities of  Giardia lamblia by halogenated bisphenols.
    Jpn J Parasitol, 35(3): 261-263.

    Kopp A (1990) [Documentation on brominated flame retardants.] Bonn,
    Federal Ministry for Environment, Nature Conservation and Reactor
    Safety (Prepared for the European Economic Community, Brussels)
    (in German).

    Lahaniatis ES, Bergheim W, & Bieniek D (1991) Formation of
    2,3,7,8-tetrabromodibenzodioxin and -furan by thermolysis of polymers
    containing brominated flame retardants. Toxicol Environ Chem,
    31/32: 521-526.

    Lorenz W & Bahadir M (1993) Recycling of Flame Retardants containing
    printed circuits: a study of the possible formation of polyhalogenated
    dibenzodioxins/-furans. Chemosphere, 26(12): 2221-2229.

    Luijk R & Govers HAJ (1992) The formation of polybrominated
    dibenzo-p-dioxins (PBDDs) and dibenzofurans (PBDFs) during pyrolysis
    of polymer blends containing brominated flame retardants. Chemosphere,
    25(3): 361-374.

    Meyer H, Neupert M, Pump W, & Willenberg B (1993) [Flame retardants
    determine reusability.] Kunststoffe, 83(4): 253-257 (in German).

    Morrissey AE (1978) The acute toxicity of FMBP4A (tetrabromobisphenol
    A) to the water flea,  Daphnia magna Straus. Tarrytown, New York,
    Union Carbide Corporation, Environmental Services (Report to Velsicol
    Chemical Corporation, Chicago, submitted to WHO by the Brominated
    Flame Retardant Industry Panel).

    Mortelmans K, Haworth S, Lawlor T, Speck W, Tainer B, & Zeiger E
    (1986)  Salmonella mutagenicity test: II. Results from the testing
    of 270 chemicals. Environ Mutagen, 8(Suppl 7): 1-119.

    Neupert M & Pump W (1992) Experiences from a large scale warehouse
    fire with bromine-containing polybutylene terephthalate forming almost
    no polybrominated dibenzodioxins and dibenzofurans. Leverkusen,
    Germany, Bayer AG (Unpublished document).

    Noda T (1985) Safety evaluation of chemicals for use in household
    products (VII): Teratological studies on tetrabromobisphenol-A in
    rats. Annu Rep Osaka City Inst Public Health Environ Sci, 48: 106-121.

    Nye DE (1978) The bioaccumulation of tetrabromobisphenol, in the
    bluegill sunfish. Santa Clara, California, Stoner Laboratories, Inc.
    (Report to Velsicol Chemical Corporation, Chicago, submitted to WHO by
    the Brominated Flame Retardant Industry Panel).

    OECD (1993) Brominated flame retardants: Draft status report. Paris,
    Organisation for Economic Cooperation and Development.

    Quast JF, Humiston CG, & Schwetz BA (1975) Results of a 90-day
    toxicological study in rats given tetrabromobisphenol A in the diet.
    Midland, Michigan, Dow Chemical (Unpublished report No. HET
    17.5-36-(3), submitted to WHO by the Brominated Flame Retardant
    Industry Panel).

    Ranken P (1993) The issue of tetrabromobisphenol A (TBBPA) and
    brominated dioxins and furans. Baton Rouge, Louisiana, Ethyl
    Corporation, Health and Environmental Department (Report submitted to
    WHO by the Brominated Flame Retardant Industry Panel).

    Satoh Y & Sugie K (1993) Brominated epoxy oligomer flame retardants -
    as one of a new generation of FRs. Tokyo, Japan, Dainippon Ink and
    Chemicals, Inc., Petrochemicals Division (Unpublished paper presented
    at the OECD Workshop on Brominated Flame Retardants, Neuchâtel,
    Switzerland, February 1993).

    Sellström U, Jansson B, Jonsson P, Nylund K, Odsjö T, & Olsson M
    (1990) Anthropogenic brominated aromatics in the Swedish environment.
    In: Short papers - Dioxin 1990, EPRI Seminar, Bayreuth, Germany,
    pp 357-360.

    Sellström U, Jansson B, & Zakrisson S (1994) [Analysis of
    tetrabromobisphenol-A in product and environmental testing.] Solna,
    Sweden, State Nature Conservation Agency (Unpublished document)
    (in Swedish).

    Steinberg CEW, Sturm A, Kelbel J, Kyu Lee S, Hertkorn N, Freitag D,
    & Kettrup AA (1992) Changes of acute toxicity of organic chemicals to
     Daphnia magna in the present of dissolved humic material. Acta
    Hydrochim Hydrobiol, 20(6): 326-332.

    Sterner W (1967) Acute oral toxicity of tetrabromo-bis-phenol A to
    rats; acute inhalation toxicity study of tetrabromo-bis-phenol A and
    acute eye irritation study on rabbits of tetrabromo-bis-phenol A. St.
    Louis, Missouri, International Bio-Research, Inc. (Report to Great
    Lakes Chemical Corporation, West Lafayette, submitted to WHO by the
    Brominated Flame Retardant Industry Panel).

    Surprenant DC (1988) Acute toxicity of tetrabromobisphenol A to
    fathead minnow  (Pimephales promelas) under flow-through conditions.
    Wareham, Massachusetts, Springborn Life Sciences, Inc. (Report No. SLS
    88-10-2834 submitted to WHO by the Brominated Flame Retardant Industry
    Panel).

    Surprenant DC (1989a) The toxicity of tetrabromobisphenol A (TBBPA)
    to fathead minnow  (Pimephales promelas) embryos and larvae. Wareham,
    Massachusetts, Springborn Life Sciences, Inc. (Report No. 89-2-2937
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Surprenant DC (1989b) The chronic toxicity of tetrabromobisphenol A
    (TBBPA) to  Daphnia magna under flow-through conditions. Wareham,
    Massachusetts, Springborn Life Sciences, Inc. (Report No. 89-01-2925
    submitted to WHO by the Brominated Flame Retardant Industry Panel).

    Surprenant DC (1989c) Acute toxicity of tetrabromobisphenol A to
    Eastern oysters  (Crassostrea virginica) under flow-through
    conditions. Wareham, Massachusetts, Springborn Life Sciences, Inc.
    (Report No. 89-1-2898 submitted to WHO by the Brominated Flame
    Retardant Industry Panel).

    Tatsukawa R & Watanabe I (1990) [Environmental problems from
    brominated organic flame retardants.] Kogai Taisaku, 26(7): 658-668
    (in Japanese)

    The Chemical Daily (1990-1994) [Special report on flame retardants.]
    Chem Daily (in Japanese).

    Thies J, Neupert M, & Pump W (1990) Tetrabromobisphenol A (TBBA), its
    derivatives and their flame retarded (FR) polymers - content of
    polybrominated dibenzo-p-dioxins (PBDD) and dibenzofurans
    (PBDF) - PBDD/F formation under processing and smouldering (worst
    case) conditions. Chemosphere, 20(10-12): 1921-1928.

    Thoma H, Rist S, Hauschultz G, & Hutzinger O (1986a) Polybrominated
    dibenzodioxins (PBrDD) and Dibenzofurans (PBrDF) in some flame
    retardant preparations, Chemosphere, 15(9-12), 2111-2113.

    Thoma H, Rist S, Hauschulz G, & Hutzinger O (1986b) Polybrominated
    dibenzodioxins and -furans from the pyrolysis of some flame
    retardants. Chemosphere, 15(5): 649-652.

    Tobe M, Kurokawa Y, Nakaji Y, Yoshimoto H, Takagi A, Aida Y, Monma J,
    Naito K, & Saito M (1986) [Subchronic toxicity study of
    tetrabromobisphenol-A: Report to the Ministry of Health and Welfare]
    (in Japanese).

    Tondeur Y, Mazac C, Freiberg M, Ranken P, Hass R, & McAllister D
    (1990) Analytical procedures for the determination of polybrominated
    dibenzo-p-dioxins and dibenzofurans in tetrabromobisphenol A and
    2,4,6-tribromophenol. Chemosphere, 20: 373-376.

    Ullmann T (1985) In: Gerhartz W, Yamamoto YS, Campbell FT, Pfefferkorn
    R, & Rounsaville JF ed. Ullmann's encyclopedia of industrial
    chemistry, 5th revis ed. Weinheim, Germany, VCH Verlagsgesellschaft,
    vol A4.

    Walsh GE, Yoder MJ, McLaughlin LL, & Lores EM (1987) Responses of
    marine unicellular algae to brominated organic compounds in six growth
    media. Ecotoxicol Environ Saf, 14: 215-222.

    Watanabe I & Tatsukawa R (1990) Anthropogenic brominated aromatics in
    the Japanese environment. In: Freij L ed. Proceedings of Workshop on
    Brominated Aromatic Flame Retardants, Skokloster, 24-26 October 1989.
    Solna, Sweden, National Chemicals Inspectorate, pp 63-71.

    Watanabe I, Kashimoto T, & Tatsukawa R (1983a) Identification of the
    flame retardant tetrabromobisphenol A in the river sediment and the
    mussel collected in Osaka. Bull Environ Contam Toxicol, 31: 48-52.

    Watanabe I, Kashimoto T, & Tatsukawa R (1983b) The flame retardant
    tetrabromobisphenol A and its metabolite found in river and marine
    sediments in Japan. Chemosphere, 12(11-12): 1533-1539.

    Zweidinger RA, Cooper SD, Erickson MD, Michael LC, & Pellizzari ED
    (1979)  Sampling and analysis for semi volatile brominated organics in
    ambient air. In: Schuetzle D ed. Monitoring toxic substances.
    Washington, DC, American Chemical Society, pp 217-231 (ACS Symposium
    Series 94).

    RESUME ET EVALUATION; CONCLUSIONS ET RECOMMANDATIONS RELATIVES AU
    TETRABROMOBISPHENOL A (TBBPA)

    1.  Résumé et évaluation

    1.1  Propriétés physiques et chimiques

         Le TBBPA se présente sous la forme d'une poudre cristalline
    blanche (incolore) contenant 59% de brome.  Son point de fusion est
    d'environ 180°C et son point d'ébullition de 316°C.  Sa tension de
    vapeur est très inférieure à 1 mmHg à 20°C.  Le TBBPA est peu soluble
    dans l'eau mais très soluble dans le méthanol et dans l'acétone.  Son
    coefficient de partage  n-octanol/eau (log Pow) est égal à 4,5.

    1.2  Production et usages

         De tous les retardateurs de flamme bromés, c'est le TBBPA du
    commerce qui est le plus produit dans le monde.  La demande de TBBPA
    et de ses dérivés représente plus de 60 000 tonnes par an.  On
    l'utilise comme retardateur de flammes réactif (usage principal) ou
    également pour cet usage, comme simple additif, dans les polymères
    tels que l'ABS, les résines époxy, les polycarbonates, le polystyrène
    choc, les résines phénoliques, les adhésifs, etc.

    1.3  Transport, distribution et transformation dans l'environnement

         Compte tenu de son coefficient de partage et de sa faible
    solubilité dans l'eau, le TBBPA présent dans l'environnement devrait
    être sujet à une importante sorption sur les sédiments et les matières
    organiques présents dans le sol.  L'étude de son accumulation dans les
    invertébrés et les vertébrés aquatiques montre que le facteur de
    bioconcentration varie de 20 à 3200.  Sa demi-vie est de moins de 1
    jour chez les poissons et de moins de 5 jour chez les huîtres.  Au
    cours de la dépuration, la majeure partie du TBBPA accumulé (et de ses
    métabolites) seront éliminés dans les 3 à 7 jours.

         Des études de biodégradation ont montré que le TBBPA était
    partiellement décomposé, dans des conditions aérobies ou anaérobies,
    dans le sol ainsi que dans les sédiments des cours d'eau et dans
    l'eau.  Selon la nature, la température, le degré d'humidité et la
    composition du sol, on a constaté que le TBBPA y subsistait encore, à
    hauteur d'environ 40 à 90%, au bout de 56 à 64 jours.  Dans les
    conditions qu'entraîne le traitement des effluents, on n'a pas
    constaté de biodégradation d'après la mesure de la DBO à 2 semaines.

         En étudiant la décomposition, par pyrolyse en laboratoire, de
    polymères contenant du TBBPA, en l'absence ou en présence de
    Sb2O3, à différentes températures ainsi qu'en présence d'oxygène,
    etc., on a constaté qu'il pouvait se former des dibenzofuranes
    polybromés (BBDF) et, dans une moindre mesure, des dibenzodi-oxines
    polybromées (BPDD).  L'analyse de polymères additionnés de TBBPA, et

    placés dans les conditions simulant un traitement thermique, n'a pas
    permis de mettre en évidence de 2,3,7,8-PBDD ou PBDF.  On a seulement
    mis en évidence des PBDF mono- ou dibromo-substitués à des
    concentrations allant jusqu'à 100 µg/kg de résine.  Des analyses
    effectuées sur l'air des lieux de travail n'ont pas permis non plus de
    déceler la présence de PBDD ou de PBDF substitués en position 2,3,7,8
    (limite de détection égale 0,1 ng/m3).

         L'analyse de polymères recyclés contenant du TBBPA a mis en
    évidence moins de 5 µg de PBDF/PBDD totaux par kg et les congénères
    substitués en position 2,3,7,8 ne s'y trouvaient qu'à des
    concentrations inférieures à 0,2 µg/kg.

         Lors de l'incendie d'un entrepôt au cours duquel une grande
    quantité de téréphtalate de polybutylène (PBT) contenant du TBBPA, a
    brûlé, on n'a décelé dans les résidus brûlés de PBT ainsi que dans des
    échantillons de cendres et de matières fondues, que de faibles
    quantités de tétra-, penta-, hexa-BDF ou BDD substitués en position
    2,3,7,8 (soit moins de 5 µg/kg).

    1.4  Concentrations dans l'environnement et exposition humaine

         Au Japon et en Suède, on a décelé la présence de TBBPA dans
    certains sédiments et au Japon encore, dans des poissons (dans deux
    échantillons sur 229 à proximité d'une zone industrielle), en
    quantités de l'ordre du mg/kg.  Dans des moules et des sédiments, on a
    pu mettre en évidence la présence du dérivé diméthoxy du TBBPA.  En
    général, on n'a pas trouvé de TBBPA dans l'eau.

    1.5  Cinétique et métabolisme chez les animaux de laboratoire et
         l'homme

         Chez le rat, la TBPPA est faiblement absorbé et au niveau des
    voies digestives.  Une fois résorbé, le composé initial et ses
    métabolites se répartissent dans la plupart des organes.  Chez le rat,
    on a observé, quel que soit le tissu, une demi-vie inférieure à 2,5
    jours.

    1.6  Effets sur les mammifères de laboratoire et les systèmes
         d'épreuve in vitro

         Le TBBPA ne présente qu'une faible toxicité aiguë par voie orale
    pour les animaux de laboratoire.  Ainsi des études ont montré que la
    DL50 par voie orale pour le rat était > 5 g/kg de poids corporel et
    qu'elle était de 10 g/kg de poids corporel pour la souris.  Chez la
    lapin, la DL50 par voie percutanée s'est révélée > 2 g/kg de poids
    corporel.  Par inhalation, le CL50 pour la souris, le rat et le
    cobaye s'est révélée > 0,5 mg/litre.  Une seule application cutanée
    de TBBPA, à des concentrations allant jusqu'à 3,16 g/kg de poids
    corporel, à des lapins et à des cobayes, n'a pas provoqué d'effets
    locaux ou généralisés.  Le TBBPA ne s'est pas révélé irritant pour la

    peau ni pour les yeux chez le lapin.  Les quelques études portant sur
    des cobayes n'ont pas permis de mettre en évidence des réactions de
    sensibilisation.  On a également recherché les possibilités
    d'induction d'une chloracné par le TBBPA sur l'oreille du lapin. 
    Aucune réaction de ce genre n'a été observée.  Une étude de toxicité
    percutanée de 3 semaines  au cours de laquelle on a badigeonné la peau
    rasée et abrasée de lapins avec du TBBPA à des concentrations allant
    jusqu'à 2500 mg/kg de poids corporel, n'a mis en évidence qu'un léger
    érythème cutané.  Aucune autre altération imputable à ce composé n'a
    été observée.

         Des rats ont été exposés à des concentrations allant jusqu'à
    18 mg/litre de TBBPA micronisé (18 000 mg/m3) pendant 2 semaines,
    4 heures par jour, 5 jours par semaine.  Aucun effet n'a été observé,
    qu'il s'agisse du poids corporel, des résultats des analyses sanguines
    et des analyses d'urine, des constantes chimiques sériques ou de
    l'histologie.

         Des doses de TBBPA allant jusqu'à 1000 mg/kg de nourriture ont
    été administrées pendant 28 jours à des rats par voie orale sans
    produire le moindre effet indésirable.  Il n'y avait aucune différence
    entre les groupes témoins et les groupes soumis aux doses élevées
    (1000 mg/kg) en ce qui concerne la teneur du foie en brome.

         Lors d'une étude de toxicité de 90 jours au cours de laquelle on
    a fait ingérer à des rats des doses de TBBPA allant jusqu'à 100 mg/kg
    de poids corporel, on n'a pas constaté d'effet indésirable sur le
    poids corporel ou le poids des organes, les paramètres hématologiques,
    les constantes chimiques, les résultats de l'analyse d'urine ainsi que
    ceux de l'examen histologique et macroscopique.

         Des souris à qui l'on a fait ingérer pendant 90 jours une dose de
    4900 mg de TBBPA/kg de nourriture (soit environ 700 mg/kg de poids
    corporel par jour) n'ont pas subi d'effet indésirable; en revanche une
    dose de 15 600 mg/kg de nourriture (soit environ 2200 mg/kg de poids
    corporel par jour) a entraîné une réduction du poids corporel, une
    augmentation du poids de la rate, une diminution de la concentration
    des hématies ainsi que de celle des protéines et des triglycérides
    sériques.

         Deux études de tératogénicité ont été effectuées sur des rats;
    l'une au cours de laquelle on a administré par gavage des
    concentrations allant jusqu'à 10 g/kg de poids corporel du 6ème au
    15ème jour de la gestation et une deuxième au cours de laquelle des
    doses allant jusqu'à 2,5 g/kg de poids corporel ont été administrées
    du jour zéro au jour 19 de la gestation.  Dans la première étude,
    trois animaux sur cinq ayant reçu 10 g/kg de TBBPA sont morts, en
    revanche aucun signe de toxicité n'a été relevé chez les animaux qui
    en avaient reçu 3 g/kg.  Aucun effet tératogène n'a été observé. 
    Quant à la deuxième étude, elle n'a pas révélé d'anomalies.

         Pour étudier le pouvoir mutagène éventuel du TBBPA, on a utilisé
    dans diverses études, les souches de  Salmonella typhimurium TA1535,
    TA1537, TA1538, TA98 et TA100, l'activation métabolique étant obtenue
    au moyen d'un mélange enzymatique S9 provenant de rats et de hamsters
    de Syrie traités par l'Aroclor; les résultats de ces études ont été
    négatifs.  Les concentrations utilisées allaient jusqu'à
    10 000 µg/boîte.  Deux épreuves effectuées sur  Saccharomyces
     cerevisiae avec ou sans préparation enzymatique microsomienne
    provenant de rats traités par l'Aroclor, ont également donné des
    résultats négatifs.

         Il n'a pas été fait état d'études de cancérogénicité ou de
    toxicité à long terme.

    1.7  Effets sur l'homme

         Le TBBP n'a pas produit d'irritation ou de sensibilisation
    cutanée chez 54 volontaires humains.

         On ne dispose d'aucune étude épidémiologique ni d'autres types de
    données sur les effets de ce produit chez l'homme.

    1.8  Effets sur les autres êtres vivants au laboratoire et dans leur
         milieu naturel

         Le TBBPA ne s'est pas révélé très toxique pour les algues
    marines.  Les valeurs de la CE50 tirées de 28 études à court terme
    se situaient dans les limites de 0,1 à 1,0 mg/litre, alors que pour
    les algues d'eau douce, on n'observait aucune inhibition de
    croissance, même à la concentration de 9,6 mg/litre.

         Pour  Daphnia magna, la CL50 aiguë à 48 heures serait de
    0,96 mg/litre; à la dose de 0,32 mg/litre, 5% des animaux sont morts. 
    Lors d'une étude de 21 jours, toutefois, on a constaté que la CE50
    correspondant à la survie et la croissance de  Daphnia magna était
    > 0,98 mg/litre.  En s'appuyant sur les effets du TBBPA sur la
    reproduction des daphnies, constatés au cours de cette même étude, on
    a obtenu une concentration de substances toxiques maximale acceptable
    se situant entre 0,30 et 0,98 mg/litre.  Pour les mysidés
    (respectivement âgés de < 1, 5 et 10 jours), les valeurs de CL50 à
    96 heures étaient respectivement égales à 0,86, 1,1 et 1,2 mg/litre.

         Chez une espèce d'huître, on a calculé que la CE50 à 96 heures
    (réduction de la formation de la coquille par dépôt calcaire) était de
    0,098 mg/litre avec une concentration sans effets observables de
    0,0062 mg/litre.

         La CL50 à 96 heures du TBBPA pour trois espèces de poissons:
     Lepomis macrochirus, la truite arc-en-ciel et  Pimephales promelas
    était respectivement égale à 0,51, 0,40 et 0,54 mg/litre.  Les
    concentrations sans effets observables pour les trois espèces de

    poissons étaient respectivement égales à 0,10, 0,18 et 0,26 mg/litre. 
    Des embryons et des larves de  Pimephales promelas ont été exposés 35
    jours à du TBBPA et on a constaté que la concentration maximale
    acceptable de substance toxique se situait entre 0,16 et
    0,31 mg/litre, à en juger d'après les effets délétères du TBBPA sur la
    survie de ces embryons et de ces larves.

         En ce qui concerne un invertébré des sédiments,  Chironomous
     tentans, on a obtenu comme valeurs de la concentration sans effet à
    14 jours, respectivement 0,039, 0,045 et 0,046 mg de TBBPA/litre d'eau
    dans des sédiments de faible, moyenne et forte teneur en carbone
    organique.

         La plupart des études portant sur des organismes aquatiques ont
    été réalisées à des pH voisins du pKa2.  Dans des eaux acides, le
    comportement du TBBPA pourrait être différent.

    2.  Conclusions

    2.1  Population générale

         On utilise largement le TBBPA incorporé à des polymères soit sous
    forme d'additif, soit sous forme réactive, comme retardateur de
    flamme.  La population générale peut entrer en contact avec cette
    substance par l'intermédiaire d'objets dans la composition desquels
    entrent ces polymères, sans que cela entraîne une absorption notable
    de TBBPA.  En outre, le toxicité du TBBPA est très faible, qu'elle
    soit aiguë ou chronique.  Ce composé est difficilement absorbé au
    niveau des voies digestives.  On peut donc en conclure que le risque
    résultant, pour la population générale, d'une exposition au TBBPA, est
    à considérer comme insignifiant.

    2.2  Exposition professionnelle

         L'exposition professionnelle au TBBPA se produit essentiellement
    par contact avec des particules lors de l'incorporation de ce produit
    comme additif, ou lors de l'emballage.  Le dépoussiérage des locaux
    grâce à une bonne ventilation ou toute autre technique, permet de
    réduire le risque pour les ouvriers.  S'il n'est pas possible
    d'éliminer convenablement les poussières, les ouvriers devront
    protéger leurs voies respiratoires.

    2.3  Environnement

         Le TBBPA que l'on retrouve dans l'environnement est
    essentiellement présent dans le sol et les sédiments.  La valeur
    relativement élevée de son facteur de bioconcentration semble être
    compensée par une excrétion rapide et ce composé n'est normalement pas
    présent dans les échantillons biologiques prélevés dans
    l'environnement.

         Dans l'environnement, il peut y avoir méthylation des groupements
    phénoliques du TBBPA, conduisant à du Me2-TBBPA qui est plus
    lipophile.  On a également retrouvé ce composé dans des sédiments,
    dans du poisson, des mollusques et des crustacés.

    2.4  Produits de décomposition

         Des traces de PBDD et de PBDF peuvent se retrouver dans le TBBPA
    comme impuretés; toutefois on n'a pas pu mettre en évidence la
    présence de congénères substitués en position 2,3,7,8.  Par pyrolyse
    au laboratoire, le TBBPA donne naissance à des PBDF et à des PBDD.

         Quelques études ont montré que, lorsqu'on procède à la
    transformation et au recyclage de polymères contenant du TBBPA sous
    forme d'additif retardateur de flammes, il ne se forme que des traces
    de ces dernières substances.

    3.  Recommandations

    3.1  Recommandations générales

    *    Les personnes qui sont employées à la fabrication du TBBPA et de
         produits qui en contiennent doivent être protégées contre toute
         exposition à cette substance par la mise en oeuvre de moyens
         techniques appropriés, la surveillance de l'exposition
         professionnelle et des mesures d'hygiène convenables.

    *    Un traitement approprié des effluents et des émissions provenant
         d'industries utilisant ce composé ou les produits qui en
         contiennent devrait permettre de réduire au minimum les cas
         d'exposition dans l'environnement.

    *    Le rejet des déchets industriels et des produits de consommation
         devrait être contrôlé afin de réduire au minimum la contamination
         de l'environnement par ce composé et ses produits de
         décomposition.

    *    Pour incinérer des produits contenant du TBBPA, on utilisera des
         appareils bien conçus fonctionnant toujours dans des conditions
         optimales.

    3.2  Etudes à effectuer

    *    Continuer à surveiller la présence de TBBPA, Me2-TBBPA, PBDF et
         PBDD dans l'environnement par analyse d'échantillons et en cas de
         résultats positifs, procéder également à une surveillance chez
         l'homme.

    *    Surveiller l'exposition professionnelle à des particules
         respirables de TBBPA; si les résultats obtenus sur les lieux de
         travail l'exigent, procéder à une étude d'inhalation à court
         terme sur des rats.

    *    Etudier la formation de PBDF et de PBDD à partir de produits
         traités par du TBBPA lors d'opérations d'incinération, incendies
         accidentels ou dans des conditions qui les simulent.

    *    Procéder à des études à long terme sur la destinée des polymères
         contenant du TBBPA (soit sous forme d'additif, soit sous forme
         réactive), notamment dans les décharges contrôlées.

    *    Etudier la transformation dans l'environnement, du TBBPA en son
         dérivé diméthylé.

    *    Poursuivre l'étude des possibilités de recyclage des polymères  
         contenant du TBBPA, en accordant une attention particulière aux
         produits de décomposition.

    *    Vu l'absence de données, il est nécessaire de procéder à une
         épreuve  in vitro supplémentaire avec le TBBPA, à la recherche
         de lésions cytogénétiques éventuelles.  En cas de résultats
         positifs, il sera nécessaire de procéder à d'autres études
          in vivo.  Si ces études donnent à leur tour des résultats
         positifs, il faudra procéder à des épreuves à court et à long
         terme complé mentaires.

    *    Vu l'absence de données, il est nécessaire d'étudier la toxicité
         du produit sur la reproduction du rat.

    ETHER DIMETHYLIQUE DU TETRABROMODISPHENOL A

         Il n'existe aucune base de données sur laquelle s'appuyer pour
    procéder à l'évaluation de l'éther diméthylique du tétrabromobisphénol
    A ni pour en justifier l'usage commercial.

         Il n'est pas possible d'évaluer l'éther diméthylique du
    tétrabromobisphénol A tant qu'on ne dispose pas de données suffisantes
    sur ses propriétés physiques et chimiques, sa production et son usage,
    son transport, sa distribution, sa transformation et sa concentration
    dans l'environnement et l'exposition humaine auxquels ils peuvent
    donner lieu, sa cinétique et son métabolisme chez l'animal et l'homme,
    ses effets sur les mammifères de laboratoire, sur l'homme ainsi que
    sur les systèmes d'épreuve in vitro; enfin, son action sur les autres
    êtres vivants, tant au laboratoire que dans leur milieu naturel.

    ETHER DIBROMOPROPYLIQUE DU TETRABROMODISPHENOL A

         Il n'existe aucune base de données sur laquelle s'appuyer pour
    évaluer l'éther dibromopropylique du tétrabromobisphénol A ni pour en
    justifier l'usage commercial.

         On peut déduire des données disponibles que la toxicité aiguë et
    à court terme de l'éther dibromopropylique du tétrabromobisphénol A
    est faible.  Cette substance a fait l'objet d'une épreuve de
    mutagénicité et l'on a constaté qu'elle se comportait comme un
    mutagène direct vis-à-vis des souches de  Salmonella typhimurium
    TA100 et TA1535.  Toutefois, les résultats d'une épreuve de synthèse
    non programmée de l'ADN et la recherche d'échanges entre chromatides
    soeurs  in vitro, ont été négatifs.

         Le produit ne pourra pas être évalué tant qu'on ne disposera pas
    de données suffisantes sur ses propriétés physiques et chimiques, sa
    production et son usage, son transport, sa distribution, sa
    transformation et sa concentration dans l'environnement et
    l'exposition humaine auxquels ils peuvent donner lieu, sa cinétique et
    son métabolisme chez l'animal et l'homme, ses effets sur les animaux
    de laboratoire et l'homme et enfin son action sur les autres êtres
    vivants au laboratoire et dans leur milieu naturel.

    ETHER DIALLYLIQUE DE TETRABROMODISPHENOL A

         Il n'existe pas de base de données sur laquelle s'appuyer pour
    évaluer l'éther diallylique de tétrabromobisphénol A ni pour en
    justifier l'usage commercial.

         D'après les données disponibles, on peut conclure que la toxicité
    aiguë par voie orale et la toxicité percutanée de ce composé sont
    faibles.  Des études d'irritation cutanée et oculaire chez le lapin
    ont montré que le composé était légèrement irritant à ce niveau.

         Ce produit ne pourra pas être évalué tant qu'on ne disposera pas
    de données suffisantes sur ses propriétés physiques et chimiques, sa
    production et son usage, son transport, sa distribution, sa
    transformation et sa concentration dans l'environnement ainsi que
    l'exposition humaine à laquelle ils peuvent donner lieu, sa cinétique
    et son métabolisme chez l'animal et l'homme, ses effets sur les
    animaux de laboratoire et sur l'homme ainsi que sur les systèmes
    d'épreuve  in vitro et enfin, son action sur les autres êtres vivants
    au laboratoire et dans leur milieu naturel.

    ETHER BIS(2-HYDROXYETHYLIQUE) DE TETRABROMODISPHENOL A

         La base de données est insuffisante pour permettre d'évaluer
    l'éther bis(2-hydroxyéthylique) de tétrabromobisphénol A ou en
    justifier l'usage commercial.

         D'après les données disponibles il semblerait que cette substance
    puisse être présente dans l'environnement.  Après administration par
    voie orale et percutanée respectivement à des rats et à des lapins, on
    a constaté que sa toxicité aiguë était faible.  Il semble également
    que sa toxicité aiguë par voie respiratoire (1 heure d'exposition)
    soit modérée chez le rat.  Une étude de toxicité à court terme sur des
    rats n'a pas permis de mettre d'effet en évidence à la dose de
    1000 mg/kg de nourriture, toutefois on a observé une augmentation
    sensible de la teneur en brome total des organes.  Le produit n'est
    pas irritant au niveau cutané ou oculaire chez le lapin.  Les
    résultats d'une étude de mutagénicité sur 5 souches de  Salmonella
     typhimurium, avec ou sans activation métabolique, ont été négatifs.

         Ce produit ne pourra pas être évalué tant qu'on ne disposera pas
    de données complémentaires sur ses propriétés physiques et chimiques,
    sa production et son usage, son transport, sa distribution, sa
    transformation et sa concentration dans l'environnement ainsi que
    l'exposition humaine à laquelle ils peuvent donner lieu, sa cinétique
    et son métabolisme chez l'animal et l'homme, ses effets sur les
    animaux de laboratoire et l'homme ainsi que sur les systèmes d'épreuve
     in vitro et enfin, son action sur les autres êtres vivants au
    laboratoire et dans leur milieu naturel.  Il est également nécessaire
    de procéder à une étude cytogénétique  in vitro.

    OLIGOMERE EPOXYDIQUE BROME DU TETRABROMODISPHENOL A

         La base de données est insuffisante pour permettre d'évaluer
    l'oligomère époxydique bromé du tétrabromobisphénol A ou pour
    justifier son usage commercial.

         On dispose de quelques données - encore qu'insuffisantes - sur
    les propriétés physiques et chimiques et sur la production et l'usage
    de l'oligomère époxydique bromé du tétrabromobisphénol A. On a
    constaté que les quantités de PBDD et de PBDF produites lors de la
    pyrolyse de résines contenant ces oligomères, sont beaucoup plus
    faibles que celles obtenues par pyrolyse du TBBPA.

         Il ne sera pas possible d'évaluer ces produits tant qu'on ne
    disposera pas de données suffisantes sur leurs propriétés physiques et
    chimiques, leur production et leur usage, leur transport, leur
    distribution, leur transformation et leur concentration dans
    l'environnement et l'exposition humaine à laquelle ils peuvent donner
    lieu, leur cinétique et leur métabolisme chez l'animal et l'homme,
    leurs effets sur les animaux de laboratoire, l'homme et les systèmes
    d'épreuve  in vitro et enfin, leur action sur les autres êtres
    vivants au laboratoire et dans leur milieu naturel.

         Comme il semble que l'on utilise de plus en plus ces composés,
    tout au moins au Japon, il est essentiel qu'ils soient étudiés plus
    avant.

    OLIGOMERES DE CARBONATE DE TETRABROMODISPHENOL A

         Il n'existe pas de base de données sur laquelle s'appuyer pour
    d'évaluer les oligomères de carbonate de tétrabromobisphénol A ni pour
    en justifier l'usage commercial.

         Les résultats d'études de mutagénicité portant sur cinq souches
    de  Salmonella typhimurium, avec ou sans activation métabolique, se
    sont révélés négatifs pour ces substances.

         Il ne sera pas possible d'évaluer ces composés tant qu'on ne
    disposera pas de données suffisantes sur leurs propriétés physiques et
    chimiques, leur production et leur usage, leur transport, leur
    distribution, leur transformation et leur concentration dans
    l'environnement et l'exposition humaine à laquelle ils peuvent donner
    lieu, leur cinétique et leur métabolisme chez l'animal et l'homme,
    leurs effets sur les animaux de laboratoire, l'homme et les systèmes
    d'épreuve  in vitro et enfin, leur action sur les autres êtres
    vivants au laboratoire et dans leur milieu naturel.  Il sera également
    nécessaire de procéder à des études cytogénétiques.

         Comme il semble que l'on utilise de plus en plus ces composés,
    tout au moins au Japon, il est essentiel qu'ils soient étudiés plus
    avant.

    RESUMEN Y EVALUACION; CONCLUSIONES Y RECOMENDACIONES SOBRE EL
    TETRABROMOBISFENOL A (TBBFA)

    1.  Resumen y evaluación

    1.1  Propiedades físicas y químicas

         El TBBFA es un polvo blanco (incoloro), cristalino, que contiene
    un 59% de bromo.  Su punto de fusión es de aproximadamente 180°C, y su
    punto de ebullición, 316°C.  Su presión de vapor es muy inferior a
    1 mmHg a 20°C.  El TBBFA es poco soluble en agua, pero es muy soluble
    en metanol y en acetona.  El coeficiente de reparto  n-octanol/agua
    (log Pow) es de 4,5.

    1.2  Producción y utilización

         El TBBFA es el pirorretardante bromado que se produce en mayor
    cantidad en el mundo.  La demanda de TBBFA y de sus derivados supera
    las 60 000 toneladas al año.  El TBBFA se utiliza como reactivo
    (utilización principal) o como aditivo pirorretardante en polímeros
    tales como las resinas ABS, epoxi y policarbonatos, poliestireno de
    alta resistencia al impacto, resinas fenólicas, adhesivos y otras
    sustancias.

    1.3  Transporte, distribución y transformación en el medio ambiente

         Debido a su coeficiente de reparto y a su escasa solubilidad en
    agua, se prevé que el TBBFA en el medio ambiente sea en gran medida
    objeto de sorción en el sedimento y en la materia orgánica del suelo.

         Los estudios sobre acumulación realizados en animales acuáticos
    invertebrados y vertebrados indican factores de bioconcentración que
    oscilan entre 20 y 3200.  La semivida en peces es de menos de un día y
    en ostras es de menos de cinco días.  Durante la depuración, la mayor
    parte del TBBFA acumulado (y sus metabolitos) se eliminan a los
    3-7 días.

         Los estudios sobre biodegradación mostraron que el TBBFA se
    degrada parcialmente en condiciones aerobias y anaerobias en el suelo
    y en el sedimento y el agua de los ríos.  Según el tipo de suelo, su
    temperatura, humedad y composición, aproximadamente el 40-90% del
    TBBFA permanece en el suelo a los 56-64 días.  En condiciones de
    tratamiento de aguas residuales, no se detectó biodegradación a las
    dos semanas cuando la biodedegradación se midió como demanda biológica
    de oxígeno.

         Los estudios sobre pirólisis en laboratorio mostraron que los
    polímeros que contienen TBBFA pueden, con o sin presencia de
    Sb2O3, a diferentes temperaturas, en presencia de oxígeno, etc.,
    formar dibenzofuranos polibromados (DFPB) y, en menor medida,

    dibenzodioxinas polibromadas (DDPB).  Se forman principalmente DFPB y
    DDPB débilmente bromados.  Cuando se analizaron polímeros formulados
    con TBBFA que se habían expuesto a condiciones de procesamiento
    térmico estimulante, no se detectaron 2,3,7,8-DDPB/DFPB.  Sólo se
    detectaron DFPB con uno o dos átomos de bromo de sustitución en
    niveles de hasta 100 µg/kg en la resina. Las investigaciones
    realizadas en el medio laboral no mostraron DDPB/DFPB con sustitución
    en las posiciones 2,3,7,8 (límite de detección: 0,1 ng/m3).

         En los polímeros reciclados que contienen TBBFA se detectaron en
    total menos de 5 µg de DFPB/DDPB por kg y los congéneres con
    sustitución en las posiciones 2,3,7,8 se encontraron solamente en
    niveles inferiores a 0,2 µg/kg.

         Tras un incendio ocurrido en un depósito en el que se quemó una
    gran cantidad de tereftalato de polibutileno (TPB) que contenía TBBFA,
    se detectaron solamente niveles bajos de dibenzofuranos tetrabromados,
    pentabromados y hexabromados y de dibenzodioxinas tetrabromadas,
    pentabromadas y hexabromadas con sustitución en las posiciones 2,3,7,8
    (menos de 5 µg/kg) en el TPB quemado y en las muestras de
    cenizas/escoria.

    1.4  Niveles ambientales y exposición humana

         Se detectó la presencia de TBBFA en algunos sedimentos en el
    Japón y en Suecia y en peces (en dos muestras extraídas cerca de una
    zona industrial, de un total de 229 muestras) en niveles del orden de
    µg/kg en el Japón.  Pudo identificarse el derivado dimetoxi del TBBFA
    en mejillones y en el sedimento.  En general, no se detectó la
    presencia de TBBFA en el agua.

    1.5  Cinética y metabolismo en animales de laboratorio y en seres
         humanos

         En las ratas, la absorción del TBBFA a través del tracto
    gastrointestinal es pobre.  Una vez absorbido, el TBBFA y/o sus
    metabolitos parecen distribuirse en la mayor parte de los órganos del
    cuerpo.  En ratas, la semivida máxima de esos compuestos en cualquier
    tejido fue de menos de dos días y medio.

    1.6  Efectos en mamíferos de laboratorio y en sistemas de prueba in
         vitro

         La toxicidad oral aguda del TBBFA para los animales de
    laboratorio es baja.  La DL50 por vía oral para la rata fue de más
    de 5 g/kg de peso corporal y la DL50 oral para el ratón fue de
    10 g/kg de peso corporal.  La DL50 por vía dérmica para el conejo
    fue de más de 2 g/kg de peso corporal.  Las CL50 por inhalación para
    el ratón, la rata y el cobayo fueron de más de 0,5 mg/litro.  Una sola
    aplicación dérmica de TBBFA en la piel de conejos y cobayos no indujo
    efectos locales o sistémicos en concentraciones de hasta 3,16 g/kg de

    peso corporal. El TBBFA no resultó irritante para la piel ni los ojos
    del conejo.  No se observó ninguna reacción de sensibilización en unos
    pocos estudios realizados en cobayos.  El TBBFA también se sometió a
    ensayos para examinar si tenía actividad cloracnegénica en las orejas
    del conejo, pero no se observó ninguna reacción de esa naturaleza.  En
    un estudio sobre toxicidad dérmica de tres semanas, en el cual se
    expuso la piel pelada y raspada de conejos a una cantidad de hasta
    2500 mg de TBBFA/kg de peso corporal, sólo se observó un eritema
    dérmico leve.  No se observaron otros cambios relacionados con el
    compuesto.

         Se expusieron ratas a una concentración de hasta 18 mg de TBBFA
    micronizado por litro (18 000 mg/m3) durante dos semanas a razón de
    4 h/día, 5 días/semana.  No se observaron efectos en el peso corporal;
    tampoco se observaron efectos histopatológicos, ni hematológicos, ni
    efectos en la química del suero ni en el análisis de la orina.

         Dosis orales de hasta 1000 mg de TBBFA/kg de dieta administradas
    durante 28 días no produjeron efectos adversos.  El contenido total de
    bromo del hígado del grupo de control no resultó diferente del grupo
    expuesto a dosis altas (1000 mg/kg).

         En un estudio sobre toxicidad en ratas se administraron por vía
    oral durante 90 días dosis de no más de 100 mg de TBBFA/kg de peso
    corporal; los exámenes del peso corporal, de la composición de la
    sangre, la química clínica, el análisis de la orina, el peso de los
    órganos y los exámenes macroscópicos y microscópicos no mostraron
    ningún efecto adverso.

         En un estudio de 90 días realizado en ratones, una dosis oral de
    4900 mg/kg de dieta (aproximadamente 700 mg/kg de peso corporal por
    día) no tuvo ningún efecto adverso; una dosis de 15 600 mg/kg de dieta
    (aproximadamente 2200 mg/kg de peso corporal por día) provocó
    disminución del peso corporal, aumento del peso del bazo y reducción
    de la concentración de eritrocitos, de proteínas del suero y de
    triglicéridos del suero.

         Se realizaron dos estudios sobre teratogenicidad en ratas, uno en
    el que se administraron con sonda dosis de hasta 10 g/kg de peso
    corporal desde el día 6 de la gestación hasta el 15 y un segundo en el
    que se administraron dosis de no más de 2,5 g/kg de peso corporal
    desde el día 0 hasta el día 19 de la gestación.  En el primer estudio,
    3 de los 5 animales que habían recibido 10 g/kg murieron, pero no se
    observaron signos de toxicidad en los animales que habían recibido
    3 g/kg.  No se observaron efectos teratogénicos.  En el segundo
    estudio no se observó ninguna anomalía.

         El TBBFA no tuvo efectos mutagénicos en diversos estudios
    realizados con cepas TA1535, TA1537, TA1538, TA98 y TA100 de
     Salmonella typhimurium cuyo metabolismo se había activado mediante
    una mezcla S9 preparada a partir de ratas y hámsters tratados con

    Aroclor.  Las concentraciones ensayadas eran de hasta
    10 000 µg/platillo.  Los resultados de dos pruebas efectuadas con
     Saccharomyces cerevisiae, con y sin el añadido de una preparación
    enzimática microsómica tomada de ratas tratadas con Aroclor, también
    resultaron negativos.

         No se comunicaron estudios sobre carcinogenicidad ni toxicidad a
    largo plazo.

    1.7  Efectos en el ser humano

         El TBBFA no produjo ninguna irritación dérmica ni sensibilización
    en 54 personas voluntarias.

         No se dispone de estudios ni de otros datos epidemiológicos sobre
    los efectos en el ser humano.

    1.8  Efectos en otros organismos en el laboratorio y en el medio
         ambiente

         El TBBFA no resultó muy tóxico para las algas marinas.  En 28
    estudios de corto plazo se observaron CE50 entre 0,1 y 1,0 mg/litro;
    las algas de agua dulce no mostraron inhibición del crecimiento, ni
    siquiera con concentraciones de 9,6 mg/litro.

         Se comunicó una CL50 aguda a las 48 horas de 0,96 mg/litro para
     Daphnia magna; con 0,32 mg/litro murieron el 5% de los organismos.
    En un estudio de 21 días, la CE50 para la supervivencia y el
    crecimiento de  Daphnia magna fue de más de 0,98 mg/litro.  Sobre la
    base de los efectos del TBBFA en la reproducción de dáfnidos en ese
    estudio de 21 días, se calculó una concentración intoxicante máxima
    aceptable de 0,3 a 0,98 mg/litro.  En mísidos (de menos de un día, de
    5 y de 10 días de edad), los valores de la CL50 a las 96 horas
    fueron de 0,86, 1,1 y 1,2 mg/litro, respectivamente.

         La CE50 aguda a las 96 horas (reducción de la deposición de la
    concha) para ostiones de Oriente se calculó en 0,098 mg/litro, con una
    concentración sin efectos observados (NOEC) de 0,0062 mg/litro.

         Las CL50 del TBBFA a las 96 horas para  Lepomis machrochirus
    trucha arco iris y  Pimephales promelas fueron de 0,51, 0,40, y
    0,54 mg/litro, respectivamente.  Las concentraciones sin efectos para
    estas tres especies ictiológicas fueron de 0,10, 0,18, y
    0,26 mg/litro.  Se expuso a  Pimephales promelas (embriones y larvas)
    durante 35 días al TBBFA y se observó una concentración intoxicante
    máxima aceptable (MATC) de 0,16 a 0,31 mg/litro, calculada sobre la
    base de los efectos adversos en la supervivencia de los embriones y
    las larvas.

         Los niveles sin efectos a los 14 días para el quironómido
    invertebrado del sedimento  Chironomous tentans fueron de 0,039,
    0,045, y 0,046 mg de TBBFA/litro de agua en sedimentos con contenido
    bajo, medio y alto, respectivamente, de carbono orgánico.

         La mayor parte de los estudios en sistemas acuáticos se han
    realizado en pH próximos al pKa2.  El comportamiento del TBBFA en
    aguas ácidas tal vez sea diferente.

    2.  Conclusiones

    2.1  Población general

         El TBBFA es muy utilizado y se incorpora en polímeros como
    reactivo o aditivo pirorretardante.  El contacto de la población
    general con el TBBFA se efectúa por intermedio de productos de esos
    polímeros y no daría lugar a una ingestión significativa de TBBFA. 
    Por otra parte, la toxicidad aguda y la de dosis repetidas de TBBFA
    son muy bajas.  La absorción del TBBFA a través del tracto
    gastrointestinal es mala.  El riesgo que para la población general
    significa la exposición al TBBFA se considera, pues, insignificante.

    2.2  Exposición ocupacional

         La exposición ocupacional al TBBFA consiste principalmente en
    exposición a partículas del mismo durante operaciones de envasado o
    mezcla.  El control del polvo mediante la ventilación del local y
    otros métodos técnicos reducirá el riesgo para los trabajadores.  Si
    el polvo no puede controlarse de manera adecuada, debe utilizarse
    protección respiratoria.

    2.3  El medio ambiente

         Las veces que se ha detectado en el medio ambiente, el TBBFA se
    ha encontrado principalmente en muestras del suelo y de sedimentos. 
    Un factor de bioconcentración relativamente elevado parece quedar
    compensado por una rápida excreción, de manera que el compuesto no se
    ha encontrado normalmente en muestras biológicas ambientales.

         Los grupos fenólicos del TBBFA se pueden metilar en el medio
    ambiente y el Me2-TBBFA resultante es más lipofílico.  Este
    compuesto también se ha hallado en el sedimento y en peces y
    crustáceos.

    2.4  Productos de la descomposición

         Se han encontrado DDPB y DFPB como trazas de impurezas en el
    TBBFA; sin embargo, no se ha demostrado la presencia de congéneres en
    posiciones 2,3,7,8.  En condiciones de pirólisis de laboratorio, se
    forman DFPB/DDPB a partir del TBBFA.

         Un número limitado de estudios han mostrado que durante la
    elaboración y el reciclado de polímeros que contienen TBBFA como
    aditivo pirorretardante pueden producirse solamente cantidades muy
    pequeñas de DFPB/DDPB.  Una ventilación apropiada y otros medios
    técnicos de control pueden prevenir la exposición de los trabajadores.

    3.  Recomendaciones

    3.1  Generalidades

    *    Los trabajadores de las plantas que fabrican TBBFA y productos
         que contienen este compuesto deben estar protegidos contra la
         exposición por medios técnicos de control, y mediante la
         vigilancia de la exposición ocupacional y la adopción de medidas
         apropiadas de higiene industrial.

    *    La exposición ambiental debe reducirse al mínimo mediante el
         tratamiento apropiado de los efluentes y emisiones en las
         industrias que utilizan el compuesto o productos del mismo.

    *    La eliminación de desechos industriales y productos de consumo
         debe controlarse para reducir al mínimo la contaminación
         ambiental con este material y con productos de su descomposición.

    *    Cuando se incinere material tratado con TBBFA, debe hacerse en
         incineradores de constitución apropiada que funcionen en
         condiciones óptimas continuas.

    3.2  Otros estudios

    *    La vigilancia de muestras ambientales de TBBFA, Me2-TBBFA y
         DFPB/DDPB debe proseguir y, si se encuentran estos compuestos,
         también debe realizarse una vigilancia en seres humanos.

    *    Debe medirse la exposición ambiental a partículas de TBBFA que
         puedan inhalarse durante la respiración; si así lo indicaran los
         resultados de la vigilancia del medio laboral, debería realizarse
         un estudio de inhalación a corto plazo en ratas.

    *    Deberían hacerse estudios sobre la formación de DFPB/DDPB a
         partir de material tratado con TBBFA durante incineraciones,
         incendios accidentales y en condiciones de simulación de
         incendios.

    *    Deberían realizarse estudios de largo plazo sobre el destino de
         los polímeros que contengan TBBFA (como resultado de la adición
         de éste al polímero o bien como resultado de una reacción),
         especialmente en vertederos.

    *    Debería estudiarse la conversión ambiental del TBBFA en sus
         derivados dimetilados, especialmente en sedimentos.

    *    Deberían proseguir los estudios sobre la reciclabilidad de los
         polímeros que contengan TBBFA, prestándose atención a los
         productos de la descomposición.

    *    Dado que no hay datos, se necesita una prueba in vitro adicional
         con TBBFA para determinar la posibilidad de daños citogenéticos.
         Si esa prueba resulta positiva, será necesario hacer estudios
          in vivo adicionales.  Si las pruebas citogenéticas  in vivo
         arrojan resultados positivos, se necesitarán pruebas adicionales
         de corto y largo plazo.

    *    Como no hay datos, se necesita una prueba sobre toxicidad
         reproductiva en ratas.

    ETER DIMETILICO DE TETRABROMOBISFENOL A

         No hay datos sobre cuya base se pueda hacer una evaluación del
    éter dimetílico de tetrabromobisfenol A ni respaldar su utilización
    comercial.

         El éter dimetílico de tetrabromobisfenol A no puede evaluarse a
    menos que se disponga de datos adecuados sobre sus propiedades físicas
    y químicas, su producción y utilización, su transporte, distribución y
    transformación en el medio ambiente, sus niveles ambientales y la
    exposición del ser humano, su cinética y metabolismo en animales y en
    seres humanos, sus efectos en mamíferos de laboratorio, en seres
    humanos y en sistemas de prueba  in vitro y sobre sus efectos en
    otros organismos en el laboratorio y en el medio ambiente.

    ETER DIBROMOPROPILICO DE TETRABROMOBISFENOL A

         No hay datos sobre cuya base se pueda hacer una evaluación del
    éter dibromopropílico de tetrabromobisfenol A ni respaldar su uso
    comercial.

         A partir de los datos disponibles puede concluirse que la
    toxicidad aguda y de corto plazo del éter dibromopropílico de
    tetrabromobisfenol A es baja.  La sustancia se sometió a pruebas para
    determinar su mutagenicidad y resultó un mutágeno directo en cepas
    TA100 y TA1535 de  Salmonella typhimurium.  Sin embargo, los
    resultados de un ensayo de síntesis no programada de ADN y de una
    prueba  in vitro de intercambio de cromátides hermanas resultaron
    negativos.

         Esta sustancia no puede evaluarse a menos que se disponga de
    datos sobre sus propiedades físicas y químicas, su producción y
    utilización, su transporte, distribución y transformación en el medio
    ambiente, sus niveles en el medio ambiente y la exposición humana, su
    cinética y metabolismo en animales y en seres humanos, sus efectos en
    mamíferos de laboratorio y en seres humanos y sus efectos en otros
    organismos en el laboratorio y en el medio ambiente.

    BIS(ALIL-ETER) DE TETRABROMOBISFENOL A

         No hay una base de datos sobre la cual hacer una evaluación del
    bis(alil-éter) de tetrabromobisfenol A, ni para respaldar su uso
    comercial.

         A partir de los datos disponibles puede concluirse que la
    toxicidad oral y dérmica aguda de este compuesto es baja.  Los
    estudios sobre irritación cutánea y ocular en conejos mostraron que la
    sustancia es levemente irritante para los ojos y la piel.

         Esta sustancia no puede evaluarse a menos que se disponga de
    datos adecuados sobre sus propiedades físicas y químicas, su
    producción y utilización, su transporte, distribución y transformación
    en el medio ambiente, sus niveles en el medio ambiente y la exposición
    humana, su cinética y metabolismo en animales y en seres humanos, sus
    efectos en mamíferos de laboratorio, en seres humanos y en sistemas de
    prueba  in vitro y sus efectos en otros organismos en laboratorio y
    en el medio ambiente.

    BIS(2-HIDROXIETIL-ETER) DE TETRABROMOBISFENOL A

         La base de datos es insuficiente para una evaluación del
    bis(2-hidroxietil-éter) de tetrabromobisfenol A o para respaldar su
    uso comercial.

         A partir de los datos disponibles, hay algunos indicios de que
    esta sustancia puede hallarse presente en el medio ambiente.  Su
    toxicidad aguda fue baja después de la administración oral y dérmica a
    ratas y conejos, respectivamente. Su toxicidad aguda por inhalación
    (1 hora de exposición) en ratas parece ser moderada.  Un estudio sobre
    toxicidad a corto plazo en ratas mostró ausencia de efectos con
    1000 mg/kg de dieta, pero se observó un aumento significativo del
    contenido total de bromo en los órganos.  No se observó que la
    sustancia irritara la piel ni los ojos de conejos.  Los resultados de
    un estudio sobre mutagenicidad en cinco cepas de  Salmonella
     typhimurium, con y sin activación metabólica, fueron negativos.

         La sustancia no puede evaluarse a menos que se disponga de datos
    adicionales sobre sus propiedades físicas y químicas, su producción y
    utilización, su transporte, distribución y transformación en el medio
    ambiente, sus niveles en el medio ambiente y la exposición del ser
    humano, sus cinética y metabolismo en animales y en seres humanos, sus
    efectos en mamíferos de laboratorio, en seres humanos y en sistemas de
    prueba  in vitro, y sus efectos en otros organismos en el laboratorio
    y en el medio ambiente.  También se necesita un estudio citogenético
     in vitro.

    EPOXI OLIGOMERO BROMADO DE TETRABROMOBISFENOL A

         La base de datos es insuficiente para una evaluación del epoxi
    oligómero bromado de tetrabromobisfenol A y para respaldar su uso
    comercial.

         Se dispone de algunos datos sobre las propiedades físicas y
    químicas y la producción y utilización del epoxi oligómero bromado de
    tetrabromobisfenol A, pero dichos datos son insuficientes.  Las
    cantidades de DDPB y DFPB producidas al pirolizar resinas que
    contienen estos epoxi oligómeros fueron menores que las producidas al
    pirolizar el TBBFA.

         Estas sustancias no pueden evaluarse a menos que se disponga de
    datos adecuados sobre sus propiedades físicas y químicas, su
    producción y utilización, su transporte, distribución y transformación
    en el medio ambiente, sus niveles ambientales y la exposición humana,
    su cinética y metabolismo en animales de laboratorio y en seres
    humanos, sus efectos en mamíferos de laboratorio, en seres humanos y
    en sistemas de prueba  in vitro, y sus efectos en otros organismos en
    el laboratorio y en el medio ambiente.

         Como la utilización de estos compuestos parece estar aumentando,
    al menos en el Japón, es esencial que se realicen más estudios.

    OLIGOMEROS DE CARBONATO DE TETRABROMOBISFENOL A

         No hay ninguna base de datos sobre la cual hacer una evaluación
    de los oligómeros de carbonato de tetrabromobisfenol A ni para
    respaldar su utilización comercial.

         Los resultados de estudios de mutagenicidad con cinco cepas de
     Salmonella typhimurium, con y sin activación metabólica, fueron
    negativos para ambas sustancias.

         Estas sustancias no pueden evaluarse a menos que se disponga de
    datos adecuados sobre sus propiedades físicas y químicas, su
    producción y utilización, su transporte, distribución y transformación
    en el medio ambiente, sus niveles ambientales y la exposición humana,
    su cinética y metabolismo en animales y en el ser humano, sus efectos
    en mamíferos de laboratorio, en seres humanos y en sistemas de prueba
     in vitro, y sus efectos en otros organismos en laboratorio y en el
    medio ambiente.  También se necesitan estudios citogenéticos
     in vitro.
    


    See Also:
       Toxicological Abbreviations