Tetrabromobisphenol A and derivatives (EHC 172, 1995)

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

The International Programme on Chemical Safety (IPCS) is a joint
venture of the United Nations Environment Programme, the International
Labour Organisation, and the World Health Organization. The main
objective of the IPCS is to carry out and disseminate evaluations of
the effects of chemicals on human health and the quality of the
environment. Supporting activities include the development of
epidemiological, experimental laboratory, and risk-assessment methods
that could produce internationally comparable results, and the
development of manpower in the field of toxicology. Other activities
carried out by the IPCS include the development of know-how for coping
with chemical accidents, coordination of laboratory testing and
epidemiological studies, and promotion of research on the mechanisms
of the biological action of chemicals.

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

The World Health Organization welcomes requests for permission to
reproduce or translate its publications, in part or in full.
Applications and enquiries should be addressed to the Office of
Publications, World Health Organization, Geneva, Switzerland, which
will be glad to provide the latest information on any changes made to
the text, plans for new editions, and reprints and translations
already available.

^(c) World Health Organization 1995

Publications of the World Health Organization enjoy copyright
protection in accordance with the provisions of Protocol 2 of the
Universal Copyright Convention. All rights reserved.

The designations employed and the presentation of the material in
this publication do not imply the expression of any opinion
whatsoever on the part of the Secretariat of the World Health
Organization concerning the legal status of any country, territory,
city or area or of its authorities, or concerning the delimitation
of its frontiers or boundaries.

The mention of specific companies or of certain manufacturers' products
does not imply that they are endorsed or recommended by the World
Health Organization in preference to others of a similar nature that
are not mentioned. Errors and omissions excepted, the names of
proprietary products are distinguished by initial capital letters.

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

Every effort has been made to present information in the criteria
monographs as accurately as possible without unduly delaying their
publication. In the interest of all users of the Environmental Health
Criteria monographs, readers are requested to communicate any errors
that may have occurred to the Director of the International Programme
on Chemical Safety, World Health Organization, Geneva, Switzerland, in
order that they may be included in corrigenda.

* * *

A detailed data profile and a legal file can be obtained from the
International Register of Potentially Toxic Chemicals, Case postale
356, 1219 Châtelaine, Geneva, Switzerland (Telephone No. 9799111).

* * *

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.

Environmental Health Criteria

PREAMBLE

Objectives

In 1973 the WHO Environmental Health Criteria Programme was
initiated with the following objectives:

(i) to assess information on the relationship between exposure to
environmental pollutants and human health, and to provide
guidelines for setting exposure limits;

(ii) to identify new or potential pollutants;

(iii) to identify gaps in knowledge concerning the health effects of
pollutants;

(iv) to promote the harmonization of toxicological and
epidemiological methods in order to have internationally
comparable results.

The first Environmental Health Criteria (EHC) monograph, on
mercury, was published in 1976 and since that time an everincreasing
number of assessments of chemicals and of physical effects have been
produced. In addition, many EHC monographs have been devoted to
evaluating toxicological methodology, e.g., for genetic, neurotoxic,
teratogenic and nephrotoxic effects. Other publications have been
concerned with epidemiological guidelines, evaluation of short-term
tests for carcinogens, biomarkers, effects on the elderly and so
forth.

Since its inauguration the EHC Programme has widened its scope,
and the importance of environmental effects, in addition to health
effects, has been increasingly emphasized in the total evaluation of
chemicals.

The original impetus for the Programme came from World Health
Assembly resolutions and the recommendations of the 1972 UN Conference
on the Human Environment. Subsequently the work became an integral
part of the International Programme on Chemical Safety (IPCS), a
cooperative programme of UNEP, ILO and WHO. In this manner, with the
strong support of the new partners, the importance of occupational
health and environmental effects was fully recognized. The EHC
monographs have become widely established, used and recognized
throughout the world.

The recommendations of the 1992 UN Conference on Environment and
Development and the subsequent establishment of the Intergovernmental
Forum on Chemical Safety with the priorities for action in the six
programme areas of Chapter 19, Agenda 21, all lend further weight to
the need for EHC assessments of the risks of chemicals.

Scope

The criteria monographs are intended to provide critical reviews
on the effect on human health and the environment of chemicals and of
combinations of chemicals and physical and biological agents. As
such, they include and review studies that are of direct relevance for
the evaluation. However, they do not describe every study carried
out. Worldwide data are used and are quoted from original studies,
not from abstracts or reviews. Both published and unpublished reports
are considered and it is incumbent on the authors to assess all the
articles cited in the references. Preference is always given to
published data. Unpublished data are only used when relevant
published data are absent or when they are pivotal to the risk
assessment. A detailed policy statement is available that describes
the procedures used for unpublished proprietary data so that this
information can be used in the evaluation without compromising its
confidential nature (WHO (1990) Revised Guidelines for the Preparation
of Environmental Health Criteria Monographs. PCS/90.69, Geneva, World
Health Organization).

In the evaluation of human health risks, sound human data,
whenever available, are preferred to animal data. Animal and
in vitro studies provide support and are used mainly to supply
evidence missing from human studies. It is mandatory that research on
human subjects is conducted in full accord with ethical principles,
including the provisions of the Helsinki Declaration.

The EHC monographs are intended to assist national and
international authorities in making risk assessments and subsequent
risk management decisions. They represent a thorough evaluation of
risks and are not, in any sense, recommendations for regulation or
standard setting. These latter are the exclusive purview of national
and regional governments.

Content

The layout of EHC monographs for chemicals is outlined below.

* Summary - a review of the salient facts and the risk evaluation
of the chemical
* Identity - physical and chemical properties, analytical methods
* Sources of exposure
* Environmental transport, distribution and transformation
* 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
* Evaluation of human health risks and effects on the environment
* Conclusions and recommendations for protection of human health
and the environment
* Further research
* Previous evaluations by international bodies, e.g., IARC,
JECFA, JMPR

Selection of chemicals

Since the inception of the EHC Programme, the IPCS has organized
meetings of scientists to establish lists of priority chemicals for
subsequent evaluation. Such meetings have been held in: Ispra, Italy,
1980; Oxford, United Kingdom, 1984; Berlin, Germany, 1987; and North
Carolina, USA, 1995. The selection of chemicals has been based on the
following criteria: the existence of scientific evidence that the
substance presents a hazard to human health and/or the environment;
the possible use, persistence, accumulation or degradation of the
substance shows that there may be significant human or environmental
exposure; the size and nature of populations at risk (both human and
other species) and risks for environment; international concern, i.e.
the substance is of major interest to several countries; adequate data
on the hazards are available.

If an EHC monograph is proposed for a chemical not on the
priority list, the IPCS Secretariat consults with the Cooperating
Organizations and all the Participating Institutions before embarking
on the preparation of the monograph.

Procedures

The order of procedures that result in the publication of an EHC
monograph is shown in the flow chart. A designated staff member of
IPCS, responsible for the scientific quality of the document, serves
as Responsible Officer (RO). The IPCS Editor is responsible for
layout and language. The first draft, prepared by consultants or,
more usually, staff from an IPCS Participating Institution, is based
initially on data provided from the International Register of
Potentially Toxic Chemicals, and reference data bases such as Medline
and Toxline.

The draft document, when received by the RO, may require an
initial review by a small panel of experts to determine its scientific
quality and objectivity. Once the RO finds the document acceptable as
a first draft, it is distributed, in its unedited form, to well over
150 EHC contact points throughout the world who are asked to comment
on its completeness and accuracy and, where necessary, provide
additional material. The contact points, usually designated by

governments, may be Participating Institutions, IPCS Focal Points, or
individual scientists known for their particular expertise. Generally
some four months are allowed before the comments are considered by the
RO and author(s). A second draft incorporating comments received and
approved by the Director, IPCS, is then distributed to Task Group
members, who carry out the peer review, at least six weeks before
their meeting.

The Task Group members serve as individual scientists, not as
representatives of any organization, government or industry. Their
function is to evaluate the accuracy, significance and relevance of
the information in the document and to assess the health and
environmental risks from exposure to the chemical. A summary and
recommendations for further research and improved safety aspects are
also required. The composition of the Task Group is dictated by the
range of expertise required for the subject of the meeting and by the
need for a balanced geographical distribution.

The three cooperating organizations of the IPCS recognize the
important role played by nongovernmental organizations.
Representatives from relevant national and international associations
may be invited to join the Task Group as observers. While observers
may provide a valuable contribution to the process, they can only
speak at the invitation of the Chairperson. Observers do not
participate in the final evaluation of the chemical; this is the sole
responsibility of the Task Group members. When the Task Group
considers it to be appropriate, it may meet in camera.

All individuals who as authors, consultants or advisers
participate in the preparation of the EHC monograph must, in addition
to serving in their personal capacity as scientists, inform the RO if
at any time a conflict of interest, whether actual or potential, could
be perceived in their work. They are required to sign a conflict of
interest statement. Such a procedure ensures the transparency and
probity of the process.

When the Task Group has completed its review and the RO is
satisfied as to the scientific correctness and completeness of the
document, it then goes for language editing, reference checking, and
preparation of camera-ready copy. After approval by the Director,
IPCS, the monograph is submitted to the WHO Office of Publications for
printing. At this time a copy of the final draft is sent to the
Chairperson and Rapporteur of the Task Group to check for any errors.

It is accepted that the following criteria should initiate the
updating of an EHC monograph: new data are available that would
substantially change the evaluation; there is public concern for
health or environmental effects of the agent because of greater
exposure; an appreciable time period has elapsed since the last
evaluation.

All Participating Institutions are informed, through the EHC
progress report, of the authors and institutions proposed for the
drafting of the documents. A comprehensive file of all comments
received on drafts of each EHC monograph is maintained and is
available on request. The Chairpersons of Task Groups are briefed
before each meeting on their role and responsibility in ensuring that
these rules are followed.

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 P_ow) 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

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°C^a,b

Boiling point 316°C (approximately)^b

Specific gravity 2.18^a

Flash point 178°C^b

Vapour pressure < 1 mmHg at 20°C^b

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°C^a
in styrene < 1.0 wt% at 25°C^a

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

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 P_ow. Using the value 4.48 of log P_ow, 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 blend^a

(a) PBDF

Temperature (°C) MBDF^b DiBDF^b TrBDF^b TeBDF^b PeBDF^b

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) MBDF^b DiBDF^b TrBDF^b TeBDF^b PeBDF^b

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 Fumes^b
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

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 P_ow 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

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°C^a

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

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

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):

EC type (tribromophenol end-capped):

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

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

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/m^3a

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/m^3a

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/m^3a

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/kg^a

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 P_ow) 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 P_ow) 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