Polybrominated dibenzo-p-dioxins and dibenzofurans (EHC 205, 1998)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

ENVIRONMENTAL HEALTH CRITERIA 205

POLYBROMINATED DIBENZO-p-DIOXINS AND DIBENZOFURANS

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 C. Melber and Dr J. Kielhorn, Fraunhofer
Institute of Toxicology and Aerosol Research, Hanover, Germany

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

World Health Organization
Geneva, 1998

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WHO Library Cataloguing in Publication Data

Polybrominated dibenzo- p-dioxins and dibenzofurans.

(Environmental health criteria ; 205)

1.Dioxins 2.Benzofurans
3.Environmental exposure 4.Occupational exposure
I.International Programme on Chemical Safety II.Series

ISBN 92 4 157205 1 (NLM Classification: QD 405)
ISSN 0250-863X

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR POLYBROMINATED DIBENZO- p-DIOXINS
AND DIBENZOFURANS

PREAMBLE

ABBREVIATIONS

1. SUMMARY

1.1. Identity, physical and chemical properties,
and analytical methods
1.2. Formation and sources of human and
environmental exposure
1.3. Environmental transport, distribution,
and transformation
1.4. Environmental levels and human exposure
1.5. Kinetics and metabolism
1.6. Effects on laboratory mammals and in vitro
test systems
1.7. Effects on humans
1.8. Effects on other organisms in the laboratory
and field

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

2.1. Identity
2.2. Physical and chemical properties
2.2.1. Appearance, melting and boiling
points, water solubility, vapour pressure,
octanol/water partition coefficient,
and sorption coefficient
2.2.2. Stability of PBDDs/PBDFs
2.2.2.1 Photolysis
2.2.2.2 Thermolytic degradation
of PBDDs/PBDFs
2.2.3. Chemical reactions

2.3. Conversion factors
2.4. Analytical methods
2.4.1. General aspects
2.4.2. Sampling and extraction
2.4.2.1 Ambient air, airborne dust,
automobile exhaust, flue gas,
and products of thermolysis
2.4.2.2 Water and aqueous samples
2.4.2.3 Environmental samples: soil,
sediment, and sewage sludge
2.4.2.4 Flame retardants, polymers,
fly ash samples, dust, soot,
and fire residues

2.4.2.5 Biological matrices: human
milk, blood/plasma, tissues,
and fish samples
2.4.3. Sample clean-up
2.4.4. Separation
2.4.5. Detection, quantification, and confirmation
of PBDDs/PBDFs by MS techniques
2.4.6. The need for analysis of
2,3,7,8-substituted congeners
2.4.7. Interfering substances
2.4.8. Standards

3. FORMATION AND SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1. Synthesis and use
3.2. By-products of brominated organic chemicals
(including flame retardants)
3.3. Formation from the photochemical degradation
of brominated organic chemicals
3.4. Formation from the laboratory thermolysis of
bromine-containing flame retardants
3.5. Formation during production of plastic materials
and presence in consumer products containing
flame retardants
3.5.1. Formation during production processes
3.5.2. Presence in resins and polymer products
3.6. Emissions from flame-retarded consumer products
3.7. Presence in fire residues, smoke condensates,
and gases after fires
3.7.1. Experimental fires
3.7.2. Accidental fires
3.8. Formation from incineration of fuels
3.9. Formation during waste disposal and treatment
3.9.1. Incineration
3.9.2. Disposal
3.9.3. Recycling
3.9.3.1 Plastics
3.9.3.2 Metals
3.10. Presence in automotive exhaust
3.11. Formation during textile processing

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

4.1. Transport and distribution between media
4.1.1. Air
4.1.2. Water and sediments
4.1.3. Soil
4.1.4. Biota
4.2. Environmental transformation
4.2.1. Photochemical degradation
4.2.2. Microbial degradation
4.3. Bioaccumulation and biomagnification

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1. Environmental levels
5.1.1. Air
5.1.1.1 Ambient air
5.1.1.2 Indoor air
5.1.2. Water and sediment
5.1.3. Soil, sewage sludge, and biocompost
5.1.4. Food and feed
5.1.5. Other products
5.1.6. Terrestrial and aquatic organisms
5.1.6.1 Plants
5.1.6.2 Animals
5.2. General population exposure
5.2.1. Exposure data
5.2.2. Monitoring of human tissues and fluids
5.3. Occupational exposure
5.3.1. Workplace monitoring data
5.3.1.1 Flame retardant/polymer industry
5.3.1.2 Offices/studios
5.3.1.3 Recycling plants
5.3.1.4 Other workplaces
5.3.2. Monitoring of human tissues and fluids

6. KINETICS AND METABOLISM

6.1. Absorption
6.1.1. Dibenzo- p-dioxins
6.1.2. Dibenzofurans
6.2. Distribution
6.2.1. Levels in organs and blood
6.2.1.1 Dibenzo- p-dioxins
6.2.1.2 Dibenzofurans
6.2.2. Transfer to offspring
6.3. Metabolic transformation
6.3.1. Dibenzo- p-dioxins
6.3.2. Dibenzofurans
6.4. Elimination and excretion
6.4.1. Dibenzo- p-dioxins
6.4.2. Dibenzofurans
6.5. Retention and turnover
6.5.1. Animal studies
6.5.2. Human studies

7. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS

7.1. Single exposure
7.1.1. Dibenzo- p-dioxins
7.1.2. Dibenzofurans
7.1.3. Remarks on the lethality of PBDDs/PBDFs
7.2. Short-term exposure
7.2.1. Dibenzo- p-dioxins
7.2.2. Dibenzofurans

7.3. Long-term exposure
7.4. Skin and eye irritation, sensitization, dermal
lesions, and acne
7.5. Reproductive and developmental toxicity
7.5.1. Reproductive toxicity
7.5.2. Developmental toxicity
7.6. Mutagenicity and related end-points
7.7. Carcinogenicity
7.7.1. Short-term studies
7.7.2. Long-term studies
7.8. Other special studies
7.8.1. Immunotoxicity
7.8.1.1 Dibenzo- p-dioxins
7.8.1.2 Dibenzofurans
7.8.2. Effects on intermediary metabolism:
Porphyrin effects
7.8.3. Effects on vitamin A storage
7.8.4. Endocrine interactions
7.8.5. Interaction with drugs and toxicants
7.8.6. Induction of microsomal enzymes
7.8.6.1 Dibenzo- p-dioxins
7.8.6.2 Dibenzofurans
7.8.6.3 Combustion products
7.9. Mechanisms of toxicity -- mode of action
7.10. Experimental data on selected PBDDs/PBDFs
and their relevance to the toxicity equivalency
factor (TEF) concept

8. EFFECTS ON HUMANS

8.1. General population exposure
8.2. Occupational/accidental exposure
8.3. Subpopulations at special risk

9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE
ENVIRONMENT

10.1. Hazard evaluation
10.2. Exposure evaluation
10.3. Risk evaluation

11. CONCLUSIONS AND RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH
AND THE ENVIRONMENT

11.1. Conclusions
11.2. Recommendations

12. FURTHER RESEARCH

13. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

REFERENCES

APPENDICES

RÉSUMÉ

RESUMEN

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
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Criteria monographs, readers are requested to communicate any errors
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A detailed data profile and a legal file can be obtained from the
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356, 1219 Châtelaine, Geneva, Switzerland (telephone no. + 41
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This publication was made possible by grant number 5 U01
ES02617-15 from the National Institute of Environmental Health
Sciences, National Institutes of Health, USA, and by financial support
from the European Commission.

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WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR POLYBROMINATED
DIBENZO- p- DIOXINS AND DIBENZOFURANS

Members

Dr A.P.J.M. de Jong, Laboratory of Organic Analytical Chemistry,
National Institute of Public Health and Environment, Bilthoven, The
Netherlands

Ms J. Diliberto, National Health and Environmental Effects
Research Laboratory, Experimental Toxicology Division, US
Environmental Protection Agency, Research Triangle Park, North
Carolina, USA

Dr M. Feeley, Toxicology Evaluation Section, Bureau of Chemical
Safety, Health Canada, Tunney's Pasture, Ottawa, Ontario, Canada
(Rapporteur)

Dr H. Fiedler, Bayerisches Institut für Abfallforschung BIFA
GmbH, Augsburg, Germany

Professor B. Jansson, Institute of Applied Environmental Research,
Stockholm University, Stockholm, Sweden (Chairman)

Dr Y. Kurokawa, Biological Safety Research Center, National
Institute of Health Sciences, Tokyo, Japan

Dr C. Melber, Fraunhofer Institute for Toxicology and Aerosol
Research, Hanover, Germany

Professor D. Neubert, Institute for Clinical Pharmacology and
Toxicology, Berlin, Germany

Professor C. Rappe, Institute of Environmental Chemistry,
University of Umea, Umea, Sweden

Observer

Dr B. Schatowitz, Environmental and Trace Analysis Consumer
Care Division, Ciba-Geigy AG, Basel, Switzerland (Representing the
European Centre for Ecotoxicology and Toxicology of Chemicals)

Secretariat

Dr H. Galal-Gorchev, International Programme on Chemical Safety,
World Health Organization, Geneva, Switzerland

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

Dr I. Mangelsdorf, Fraunhofer Institute for Toxicology and Aerosol
Research, Hanover, Germany

Dr F.X.R. van Leeuwen, Chemical Safety, European Centre for
Environment and Health, Bilthoven Division, De Bilt, The Netherlands

ENVIRONMENTAL HEALTH CRITERIA FOR POLYBROMINATED DIBENZO- p-DIOXINS
AND DIBENZOFURANS

A WHO Task Group on Environmental Health Criteria for
Polybrominated Dibenzo- p-dioxins and Dibenzofurans met at the
Fraunhofer Institute for Toxicology and Aerosol Research, Hanover,
Germany from 11 to 15 November 1996. Professor U. Heinrich opened the
meeting and welcomed the participants on behalf of the host institute.
Dr H. Galal-Gorchev, IPCS, welcomed the participants on behalf of the
Director, IPCS, and the three IPCS cooperating organizations
(UNEP/ILO/WHO). The Task Group reviewed and revised the draft criteria
monograph and made an evaluation of the risks for human health and the
environment from exposure to polybrominated dibenzo- p-dioxins and
dibenzofurans.

Dr J. Kielhorn and Dr C. Melber, Fraunhofer Institute for
Toxicology and Aerosol Research, Hanover, Germany, prepared the first
draft of this monograph. They also prepared the second draft,
incorporating comments received following the circulation of the first
draft to the IPCS Contact Points for Environmental Health Criteria
monographs.

Dr H. Galal-Gorchev, IPCS Central Unit, was responsible for the
overall scientific content and Ms M. Sheffer, Scientific Editor,
Ottawa, Canada, for the linguistic editing.

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

ABBREVIATIONS

ABS acrylonitrile-butadiene-styrene
Ah aromatic hydrocarbon
AHH arylhydrocarbon hydroxylase
BB bromobiphenyl
BDE bromodiphenyl ether
CAS Chemical Abstracts Service
CYP cytochrome P-450
DBB/decaBB decabromobiphenyl
DBDE/decaBDE decabromodiphenyl ether
DD/DF dibenzo- p-dioxin/dibenzofuran
DiBDD dibromodibenzo- p-dioxin
DiBDF dibromodibenzofuran
DiXDF mixed dihalogenated dibenzofuran
EC₅₀ median effective concentration
ED₅₀ median effective dose
EI-SIM-MS electron impact-selective ion monitoring-mass
spectrometry
EPA Environmental Protection Agency (USA)
EROD ethoxyresorufin- O-deethylase
GC gas chromatography
HexaBB hexabromobiphenyl
HIPS high-impact polystyrene
HpBDD/heptaBDD heptabromodibenzo- p-dioxin
HpBDF/heptaBDF heptabromodibenzofuran
HPLC high-performance liquid chromatography
HRGC high-resolution gas chromatography
HRMS high-resolution mass spectrometry
HxBDD/hexaBDD hexabromodibenzo- p-dioxin
HxBDF/hexaBDF hexabromodibenzofuran
HxCDD/hexaCDD hexachlorodibenzo- p-dioxin
I-TEF international toxicity equivalency factor
I-TEQ international toxic equivalent
LD₅₀ median lethal dose
LOAEL lowest-observed-adverse-effect level
LOEL lowest-observed-effect level
MI-IR matrix isolation infrared spectrometry
MoBDD/monoBDD monobromodibenzo- p-dioxin
MoBDF/monoBDF monobromodibenzofuran
MS mass spectrometry
n sample size
NCI negative ion chemical ionization
n.d. not detected
NOAEL no-observed-adverse-effect level
NOEL no-observed-effect level
n.sp. not specified
OBDE/octaBDE octabromodiphenyl ether
OcBDD/octaBDD octabromodibenzo- p-dioxin
OcBDF/octaBDF octabromodibenzofuran
OCDD/OcCDD/octaCDD octachlorodibenzo- p-dioxin
PAH polycyclic aromatic hydrocarbon

PBB polybrominated biphenyl
PBDD polybrominated dibenzo- p-dioxin
PBDE polybrominated diphenyl ether
PBDF polybrominated dibenzofuran
PBT polybutylene terephthalate
PCB polychlorinated biphenyl
PCDD polychlorinated dibenzo- p-dioxin
PCDE polychlorinated diphenyl ether
PCDF polychlorinated dibenzofuran
PeBDD/pentaBDD pentabromodibenzo- p-dioxin
PeBDE/pentaBDE pentabromodiphenyl ether
PeBDF/pentaBDF pentabromodibenzofuran
PeCDF/pentaCDF pentachlorodibenzofuran
PeHDD pentahalogenated dibenzo- p-dioxin
PeHDF pentahalogenated dibenzofuran
PHDD polyhalogenated dibenzo- p-dioxin (used as
collective term including PCDD, PBDD, PXDD)
PHDF polyhalogenated dibenzofuran (used as collective
term including PCDF, PBDF, PXDF)
PVC polyvinyl chloride
PXDD mixed (brominated/chlorinated) halogenated
dibenzo- p-dioxin
PXDF mixed (brominated/chlorinated) halogenated
dibenzofuran
RI retention index
RIA radioimmunoassay
RMM relative molecular mass
SD standard deviation
T₃ triiodothyronine
T₄ thyroxin
TBBPA tetrabromobisphenol A
TBCDD 2,3-dibromo-7,8-dichlorodibenzo- p- dioxin
TBDD/2,3,7,8-TeBDD 2,3,7,8-tetrabromodibenzo- p-dioxin
TBDF/2,3,7,8-TeBDF 2,3,7,8-tetrabromodibenzofuran
TBPI bis-tetrabromo-phthalimide ethylene
TCDD/2,3,7,8-TeCDD 2,3,7,8-tetrachlorodibenzo- p-dioxin
TCDF/2,3,7,8-TeCDF 2,3,7,8-tetrachlorodibenzofuran
TeBDD/tetraBDD tetrabromodibenzo- p-dioxin
TeBDF/tetraBDF tetrabromodibenzofuran
TEF toxicity equivalency factor
TeHDD tetrahalogenated dibenzo- p-dioxin
TEQ toxic equivalent
TeXDD/tetraXDD mixed tetrahalogenated dibenzo- p- dioxin
THDF 2,3,7,8-tetrahalogenated dibenzofuran
TrBDD/triBDD tribromodibenzo- p-dioxin
TrBDF/triBDF tribromodibenzofuran
TrHDD/triHDD trihalogenated dibenzo- p-dioxin
TV television
TxDD 2,3,7,8-substituted mixed tetrahalogenated
dibenzo- p-dioxin
UV ultraviolet
WHO World Health Organization

1. SUMMARY

1.1 Identity, physical and chemical properties, and analytical
methods

Polybrominated dibenzo- p-dioxins (PBDDs) and polybrominated
dibenzofurans (PBDFs) are almost planar tricyclic aromatic compounds.
Theoretically, 75 PBDDs and 135 PBDFs are possible. In addition, a
large number of mixed halogenated congeners -- 1550
brominated/chlorinated dibenzo- p-dioxins (PXDDs) and 3050
brominated/chlorinated dibenzofurans (PXDFs) -- are theoretically
possible. Because of the complexity of the analytical procedures and
paucity of analytical reference standards, it has been possible to
characterize and determine only a small number of these compounds. The
most toxic congeners are those substituted at positions 2, 3, 7, and
8. There are 7 2,3,7,8-substituted PBDDs and 10 2,3,7,8-substituted
PBDFs, as well as 337 possible 2,3,7,8-substituted PXDDs and 647
possible 2,3,7,8-substituted PXDFs.

PBDDs/PBDFs have higher molecular weights than their chlorinated
analogues, high melting points, low vapour pressures, and low water
solubilities. They are generally soluble in fats, oils, and organic
solvents. There are very few experimental data on the physical and
chemical properties of PBDDs/PBDFs.

Photolysis occurs at a more rapid rate for PBDDs/PBDFs than for
polychlorinated dibenzo- p-dioxins (PCDDs) and polychlorinated
dibenzofurans (PCDFs). PBDDs/PBDFs are thermostable. The temperatures
of formation and destruction of PBDDs/PBDFs depend on several
conditions, including the presence or absence of oxygen, polymers, and
flame retardant additives, such as antimony trioxide (Sb₂O₃).

In the presence of excess chlorine, bromine is substituted by
chlorine to give PXDDs/PXDFs.

Because of the toxic nature of these compounds and their
photolytic properties, care must be taken during sampling and
analysis. Highly sensitive, selective, and specific analytical methods
(gas chromatography/mass spectrometry, or GC/MS) are required because
of the large number of PBDD/PBDF congeners. Sampling procedures are
identical for all polyhalogenated dibenzo- p-dioxins (PHDDs) and
polyhalogenated dibenzofurans (PHDFs), but separation and
determination of PBDDs/PBDFs (and PXDDs/PXDFs) differ slightly from
those of their chlorinated analogues. PBDDs/PBDFs have higher
molecular weights and longer GC retention times than the chlorinated
analogues, as well as different MS isotopic cluster patterns and
interference compounds. Exact identification of specific brominated
congeners is very limited owing to the small number of reference
standards currently available. For the same reason, determination of
mixed halogenated congeners is almost impossible.

1.2 Formation and sources of human and environmental exposure

PBDDs/PBDFs are not known to occur naturally. They are not
intentionally produced (except for scientific purposes) but are
generated as undesired by-products in various processes. They can be
formed by chemical, photochemical, or thermal reactions from
precursors and by so-called de novo synthesis.

PBDDs/PBDFs have been found as contaminants in brominated organic
chemicals (e.g. bromophenols) and, in particular, in flame retardants,
such as polybrominated diphenyl ethers (PBDEs), decabromobiphenyl
(decaBB or DBB), 1,2-bis(tribromophenoxy)ethane, tetrabromobisphenol A
(TBBPA), and others. They have been detected in distillation residues
of some bromophenols and bromoanilines and in wastes from chemical
laboratories.

PBDFs and, to a lesser extent, PBDDs have been detected as
photochemical degradation products of brominated organic chemicals,
such as PBDEs and bromophenols.

Laboratory thermolysis experiments showed the formation of
PBDDs/PBDFs from bromophenols, PBDEs, polybrominated biphenyls (PBBs),
and other brominated flame retardants (pure or in a polymer matrix).
There was a broad range of yields, from zero to maximum values
(reached from PBDEs) in the g/kg range. Generally, PBDFs were much
more abundant than PBDDs. The optimum PBDF formation temperature of a
series of pure flame retardants was in the range of 600-900°C. The
presence of polymers or synergists (e.g. Sb₂O₃) resulted in a
decrease in the optimum formation temperature (down to 400°C). In
addition to temperature and the presence of polymer matrix or
synergists, several other factors, such as metals, metal oxides,
water, oxygen, and the type of combustion apparatus used, influenced
the yield and pattern of PBDDs/PBDFs. In ternary mixtures of PBDE,
polymer matrix, and Sb₂O₃, tetrabromodibenzo furans (tetraBDFs or
TeBDFs) were frequently the most abundant homologue group.
2,3,7,8-Substituted PBDDs/PBDFs (tetra to hepta) were found at varying
concentrations; for example, 2,3,7,8-TeBDF was found at up to 2000
mg/kg in pyrolysates of polymers containing octabromodiphenyl ether
(octaBDE or OBDE).

In the manufacture of plastics, elevated temperatures (150-300°C)
occur during several processes. Studies of the exhaust streams from
machines processing polymers -- such as
acrylonitrile-butadiene-styrene (ABS) and polybutylene terephthalate
(PBT) -- containing different types of brominated flame retardants
showed that PBDDs/PBDFs (di to octa) can be formed at these
temperatures. OBDE and decabromodiphenyl ether (decaBDE or DBDE)
produced the highest amounts of PBDDs/PBDFs, the major portion
consisting of PBDFs. Levels observed with TBBPA or
bis-tetrabromo-phthalimide ethylene (TBPI) were several orders of
magnitude lower. No PBDDs/PBDFs were detected during processing of ABS
flame-retarded by brominated styrene or

1,2-bis(tribromophenoxy)ethane. 2,3,7,8-Substituted congeners were not
determined (processing of DBDE), were detected at trace levels
(processing of OBDE), or were not detected (processing of TBBPA and
TBPI).

Various plastic materials at several processing stages were
analysed for PBDDs/PBDFs. These included (granulated) resins and
moulded parts whose flame retardant additives were known as well as
samples from commercial electrical appliances (television sets,
printers, computers) whose flame retardant additives were unknown. The
highest levels of PBDDs/PBDFs were found in materials flame-retarded
with PBDEs and were in the range of several thousand µg/kg, thus
exceeding the levels of other flame retardant/polymer systems by
orders of magnitude. Factors influencing the extent of formation are
temperature and the duration of such processes as blending, extrusion,
and moulding. Again PBDFs dominated, with some exceptions, over PBDDs,
with the highly brominated (>tetra) derivatives being prevalent. Peak
concentrations were seen with pentabromodibenzofurans (pentaBDFs or
PeBDFs) and hexabromodibenzofurans (hexaBDFs or HxBDFs). The latter
reached levels as high as 3000 µg/kg in casing parts. Printed circuit
boards contained tetra- and pentaBDFs at maximum concentrations of
1300 and 1400 µg/kg, respectively. Total PBDF (mono to hexa)
concentrations were in the range of 3.6-3430 µg/kg.
2,3,7,8-Substituted PBDDs/PBDFs were not determined, were not
detectable, or were present at relatively low concentrations. Maximum
concentrations of 2,3,7,8-substituted PBDFs (tetra to hexa) in casings
or printed circuit boards ranged from 11 µg/kg (tetra) to 203 µg/kg
(hexa).

Experiments to determine whether PBDFs were released from
television sets or similar appliances during use showed air levels
ranging from not detected to 1800 pg total PBDFs (tetra to hexa) per
appliance.

Burning of products containing brominated compounds caused
emission of PBDDs/PBDFs. In experimental fire tests simulating real
fire conditions with electrical appliances such as television sets,
printers, computer terminals, and their casings, high PBDF (mono to
hexa) concentrations were detected in the combustion residues
(thousands of mg/kg), in smoke condensate (hundreds of µg/m²), and in
smoke (up to 1700 µg/m³). PBDD concentrations amounted to about 3% of
the detected levels of PBDDs/PBDFs. The 2,3,7,8-substituted isomer was
mostly below 3% of the total tetraBDFs. 2,3,7,8-Substituted penta- and
hexaBDFs yielded between 1 and 16% of the corresponding totals.
Burning of test vehicles resulted in PBDF (mono to octa)
concentrations of up to 4.3 µg/kg in the fire residues.

During real fire accidents in private residences (television sets
involved), offices (computers involved), and other buildings,
concentrations measured were in most cases below the values found in
the model experiments described above, but the qualitative composition
of the samples was similar. PBDFs were found in almost all samples,
but PBDDs were not always detected; if present, their concentrations

were low. The PBDF concentrations in combustion residues were mainly
in the µg/kg range (low to high), but single maximum values (sum of
mono to hexa) of up to 107 mg/kg were also observed. The PBDF (mono to
hexa) area contaminant concentrations in close vicinity to the fire
site ranged between 0.1 and 13 µg/m² in most cases. Additionally,
relevant concentrations of PXDDs/PXDFs could be detected. The
proportion of 2,3,7,8-substituted PBDDs/PBDFs was relatively low in
most of the samples examined. For example, maximum proportions of 3,
10, or 18% of the corresponding totals of tetra-, penta-, or hexaBDFs,
respectively, were reported from fire accidents with television sets.
Soot samples collected after a fire in a computer room contained
2,3,7,8-substituted tetra- and pentabromodibenzo- p-dioxins
(tetra/pentaBDDs or TeBDD/PeBDD) and tetra- and pentaBDFs, with a
maximum concentration of 48 µg/kg for 2,3,7,8-TeBDF (TBDF).

PXDDs were detected in ash from a wood-fired boiler. However, the
sort of wood (treated or untreated) was not specified. No data were
available on the incineration of other fuels, such as coal, peat, or
fuel oil.

The presence of PBDDs/PBDFs and/or PXDDs/PXDFs has been reported
in fly ash and/or flue gas of municipal, hospital, or hazardous waste
incinerators. The majority of these compounds are probably produced in
the incinerator itself, by formation from precursors at high
temperatures in the flame or by de novo synthesis at low
temperatures in the post-combustion zone of the incinerator. The
formation of PXDDs/PXDFs is explained by the extensive
bromine-chlorine exchange reactions (with chlorine donors in waste)
observed under several test conditions. The quantities of PBDDs/PBDFs
and PXDDs/ PXDFs measured in fly ash of incinerators were in the range
of ng/kg to µg/kg. In most cases, the concentrations of
dibenzo- p-dioxins exceeded those of dibenzofurans, and PXDDs/PXDFs
were more abundant than PBDDs/PBDFs. Of 2,3,7,8-substituted congeners,
a mixed tetrahalogenated dibenzo- p-dioxin (tetraXDD or TeXDD)
(Br₂Cl₂DD) was found.

Analyses of waste samples from some disposal sites showed the
presence of PBDDs/PBDFs and PXDDs/PXDFs at concentrations of several
hundred to several thousand ng/kg dry weight. The concentration of
dibenzo- p-dioxins (up to 580 ng/kg) was below that of dibenzofurans
(up to 4230 ng/kg). Generally, the homologue profile was dominated by
the lower halogenated (mono to tetra) derivatives. Chemical laboratory
waste contained PBDDs/PBDFs, with a peak concentration of 15 500 ng/kg
for hexaBDFs.

PBDDs/PBDFs were present in plastic materials (with or without
metals) of several recycling stages. The samples originated mainly
from office machines, printed circuit boards, and other electronic
scrap. In some cases, the sum concentration of eight selected PBDD/
PBDF congeners having the 2,3,7,8-substitution was as high as 65
µg/kg. Metal reclamation was also found to be a source of PBDDs and/or
PXDDs/PXDFs. PBDDs/PBDFs have also been detected in textile industries

where brominated flame retardants have been used. PBDFs were found in
the exhaust air, in the textiles before and after processing, and in
the chimney depositions.

PBDDs/PBDFs and PXDDs/PXDFs (along with PCDDs/PCDFs) have been
detected in emissions of motors using leaded petrol, in emissions of
motors using unleaded petrol with and without catalytic converters,
and in emissions of diesel engines. Because of the brominated and
chlorinated scavengers (dibromo- and dichloroethane) used in leaded
petrol, the highest levels of PHDDs/PHDFs (several thousand ng/m³)
were found with this type of petrol. Unleaded petrol produced much
lower emissions of PHDDs/PHDFs (approximately two orders of magnitude
lower). A further reduction was seen after catalytic gas cleaning. The
values for diesel engines were somewhat higher than those found with
the Otto motors (spark ignition engines) run on unleaded petrol. In
exhaust gases from combustion of leaded petrol, PBDDs/PBDFs were more
abundant than PXDDs/PXDFs and PCDDs/PCDFs. Generally, the
concentrations of dibenzofurans exceeded those of dibenzo- p-dioxins,
and there was a dominance of lower substituted homologues (mono to
tri). Similar patterns were seen in residues adhering to mufflers.

1.3 Environmental transport, distribution, and transformation

There are very few data available on the environmental transport
and distribution of PBDDs/PBDFs. Generally, their physicochemical
properties suggest similarities to PCDDs/PCDFs. Therefore, if released
to the environment, they may be preferably distributed into carbon- or
fat-rich compartments, as with PCDDs/PCDFs.

Airborne PBDDs/PBDFs were found to be transported in both the
particulate and vapour phase, the partitioning ratio depending on the
degree of bromination.

No experimental data are available on the movement of PBDDs/
PBDFs in water or soil. For PBDFs (tri to penta), adsorption to
sediment was reported. Owing to the low water solubility of PBDDs/
PBDFs, leaching through the soil may be limited but may be increased
in the presence of organic solvents or humic acids.

There are no experimental data on processes for the transport and
distribution of PBDDs/PBDFs between environmental media and biota or
within biota. Based on the similar high octanol/water partition
coefficients calculated for selected PCDDs/PCDFs, PBDDs/PBDFs, and
PXDDs/PXDFs, a bioavailability comparable to that of PCDDs/ PCDFs is
expected.

Photolysis of PBDDs/PBDFs and PXDDs/PXDFs was studied in organic
solvents and on quartz surfaces in the laboratory, as well as in soil
and on soot (and dust) particles under outdoor conditions. The slowest
photolytic reactions were observed under the latter, more
environmentally relevant, conditions. Reductive debromination was
found to be a major photochemical pathway. The rate of decomposition

of different congeners depended on their bromine substitution pattern.
Generally, higher brominated congeners and those with lateral bromines
had shorter half-lives. Calculated half-lives were in the order of
minutes (use of direct sunlight or ultraviolet [UV] light and quartz
vials), hours (use of solid films or soot or dust particles and
sunlight), or hundreds to thousands of hours (use of soil and
sunlight). For example, the estimated sunlight-induced half-lives for
2,3,7,8-TeBDD (TBDD) were 0.8 min (in organic solution) or 32 h
(dispersed as solid films). A half-life of 3-6 months was estimated
for tetraBDD isomers in surface soil. Compared with PCDDs/PCDFs, the
brominated counterparts were photochemically less stable. PXDDs/PXDFs
preferentially lost their bromine atoms during photolysis and
therefore were transformed into PCDDs/PCDFs, which had longer
photolytic half-lives. Such a transformation of PXDDs/PXDFs to
PCDDs/PCDFs also occurs during incineration processes.

PBDDs/PBDFs seem to be poorly degradable by microorganisms.

The presence of PBDDs/PBDFs in animals and in humans, as seen in
a few studies, is indicative of their accumulation potential.
2,3,7,8-TeBDD accumulated in rats during subchronic administration.
Bioaccumulation, bioconcentration, or biomagnification factors for
PBDDs/PBDFs or PXDDs/PXDFs are not available.

1.4 Environmental levels and human exposure

To date, in contrast to PCDDs/PCDFs, PBDDs/PBDFs have not been
frequently included in monitoring programmes. The few studies
performed indicate a limited occurrence.

In ambient air, PBDFs were found more frequently than PBDDs. Only
lower brominated PBDDs (mono to tetra) were detected at concentrations
ranging from not detected (n.d.) to about 0.85 pg/m³ for
monobromodibenzo- p-dioxins (monoBDDs or MoBDDs) in a motor way
tunnel and an underground garage. Of PBDFs, mono- to hexabrominated
homologues were found, their concentrations ranging from n.d. to 74
pg/m³. The concentrations (mean values) of total PBDDs/ PBDFs (tri to
hexa) measured, for example, in Germany in a motorway tunnel, in a
city, and in a suburban area amounted to 23 pg/m³, 2 pg/m³, and 0.59
pg/m³, respectively; 2,3,7,8-TeBDD was not detected, and the maximum
concentrations of 2,3,7,8-TeBDF and 1,2,3,7,8-PeBDF were 0.28 pg/m³
and 0.08 pg/m³, respectively. PXDFs were identified in
traffic-related air samples at concentrations up to 41 pg/m³
(Cl₁Br₁DFs). Outdoor dust samples (mainly from motorways) also
showed a predominance of PBDFs/PXDFs (maxima of several thousand
ng/kg) over PBDDs/PXDDs (maxima of up to some hundred ng/kg).

Indoor air samples taken from rooms equipped with a number of
operating electronic appliances (television and/or computer monitors)
showed the presence of PBDFs (tetra to hepta) at total concentrations
ranging from 0.23 to 1.27 pg/m³. PBDDs were not detected. Dust
samples collected in computer rooms yielded total PBDF levels of

2.4-5.5 µg/kg dust. In contrast to air, the homologue pattern in dust
was dominated by hexaBDFs and heptabromodibenzofurans (heptaBDFs or
HpBDFs). Only in dust samples were low concentrations of tetraBDDs (up
to 1 µg/kg) and of 2,3,7,8-substituted tetra- and pentaBDFs (up to
0.07 µg/kg) detectable. PBDF concentrations in the one sample of house
dust were lower by a factor of 10. The sum concentration of
PBDDs/PBDFs equalled that of PCDDs/PCDFs in dust from computer rooms
but was lower than that of PCDDs/PCDFs in house dust. Dust from an
underground garage contained lower halogenated PBDFs (mono and di) and
PXDFs (di to tetra), with a maximum concentration of 4.3 µg/kg for
mixed dihalogenated dibenzofurans (DiXDFs).

No data are available on levels of PBDDs/PBDFs in water samples.

In river and marine sediment samples from an industrialized zone,
tetraBDDs (up to 0.006 µg/kg dry weight) and tetra- to hexaBDFs (sum
up to 0.37 µg/kg dry weight) were detected. Sediment from road
drainage contained PBDFs (sum of mono to tri: 2.5 µg/kg; sum of tetra
to hepta: 0.3 µg/kg) and PXDFs (sum of di and tri: 1.85 µg/kg), but no
PBDDs.

Similarly, soil samples taken near a motorway contained
monobromodibenzofurans (monoBDFs or MoBDFs) and dibromodibenzofurans
(DiBDFs) (sum: 1.3 µg/kg), tetra- and pentaBDFs (sum: 0.02 µg/kg), and
PXDFs (sum: 1 µg/kg), but no PBDDs. Soil samples taken from an
incineration field and near a metal reclamation factory gave total
PBDF concentrations of up to 100 µg/kg, but no PBDDs were detected. In
a series of sewage sludge samples from municipal wastewater treatment
plants, total PBDF concentrations ranged from n.d. to 3 µg/kg. In one
case, traces of tetraBDDs and 2,3,7,8-TeBDF were detected. A
biocompost sample was nearly free of PBDDs/ PBDFs (tetraBDFs: <0.003
µg/kg).

There are no quantitative data on levels of PBDDs/PBDFs in food.

In grass and pine needle samples collected near motorways, lower
halogenated PBDFs/PXDFs (mono to tetra) and traces of PBDDs/ PXDDs
(mono to tri) were detectable.

No PBDDs/PBDFs were found in the few wildlife samples tested.

In cow's milk collected at dairy farms in the vicinity of a
municipal waste incinerator, tribromodibenzofurans (triBDFs or
TrBDFs), a tetraBDF, and a pentaBDF (not having the
2,3,7,8-substitution pattern) were tentatively identified.

PBDDs/PBDFs have not been detected in the few tested samples of
human adipose tissues or milk samples from the general public.

Contamination by PBDDs/PBDFs is possible at a variety of
workplaces involved in the production, processing, use, or disposal of
certain flame retardants or their products, especially where processes
involve elevated temperatures. The magnitude of worker exposure

depends not only on the compounds involved but also on the quality of
the air and ventilation conditions. There are only limited workplace
monitoring data from plastic producing or processing facilities, from
offices/studios with large numbers of electrical appliances
continuously in use, and from recycling workplaces (including
secondary copper plants). Generally, PBDFs were more abundant than
PBDDs, and PBDF air concentrations were highest at workplaces where
DBDE-containing polymers were produced. In many samples,
2,3,7,8-substituted PBDFs/PBDDs were detectable. PBDD/PBDF
contamination was also found at the work area under the fume hood of a
chemical laboratory. Monitoring data at waste incineration facilities
are lacking.

1.5 Kinetics and metabolism

Most of the studies refer to 2,3,7,8-TeBDD and, to a lesser
extent, 1,2,7,8-TeBDF. Half-life calculations have included some
additional congeners.

2,3,7,8-TeBDD was absorbed in rats after oral, intratracheal, and
dermal administration, the percent absorption varying with route and
dose. Single doses of 1 nmol 2,3,7,8-TeBDD/kg body weight led to an
absorption of 80% (oral and intratracheal routes) or 12% (dermal
route) of the administered dose. The dermal absorption of 1 nmol
1,2,7,8-TeBDF/kg body weight was about 29%. Oral absorption of
2,3,7,8-TeBDD appeared to be comparable to that of
2,3,7,8-tetrachlorodibenzo- p-dioxin (2,3,7,8-TeCDD or TCDD).
However, dermal absorption of 2,3,7,8-TeBDD was about one-third that
of an equimolar dose of 2,3,7,8-TeCDD.

2,3,7,8-TeBDD or 1,2,7,8-TeBDF administered to rats, by any
route, was distributed throughout the entire body, with major deposits
found in liver and adipose tissue, followed by skin and muscle. For
example, 3 days after single oral doses of 2,3,7,8-TeBDD (1 nmol/kg
body weight), the portions in these tissues amounted to 20%, 20%, 11%,
and 4%, respectively, whereas thymus and adrenals contained 0.03% and
0.4%, respectively, of the administered dose. The partitioning of
2,3,7,8-TeBDD between liver and adipose tissue of rats was found to be
influenced by dose, route of exposure, and time post-dosing. The
ratios of liver : fat concentrations measured under different
conditions ranged from 0.2 to 6.5 (range for single doses of
2,3,7,8-TeBDD in rats). No experimental data were available on the
transfer of PBDDs/PBDFs to offspring.

TetraBDD/BDF metabolites were detected in bile and faeces from
rats. They were mainly formed by aromatic hydroxylation and hydrolytic
debromination. The rate of metabolism (indirectly determined as the
rate of biliary excretion) differed between 2,3,7,8-TeBDD (about 7%)
and 1,2,7,8-TeBDF (about 50%). Three days after an intravenous dose of
2,3,7,8-TeBDD (1 nmol/kg body weight), 14% of the administered dose
was found as metabolites in the faeces of rats.

Elimination and excretion of 2,3,7,8-TeBDD were studied in rats
using oral, intravenous, intratracheal, and dermal routes of
administration. In all studies, the major route of elimination was
through the faeces, the eliminated radioactivity ranging from 2%
(dermal route) to 42% (oral route) of the administered dose (1 nmol
[³H]2,3,7,8- TeBDD/kg body weight) in faeces samples, and from 0.2 to
1% in urine samples. Similarly, in studies with 1,2,7,8-TeBDF in rats,
excretion was mainly through the faeces, only 2-3% of the intravenous,
oral, or dermal doses being excreted in urine. During the first days
following oral doses, unabsorbed material and biliary excretion
appeared to be the major sources of eliminated compound in faeces. The
portions of parent 2,3,7,8-TeBDD found in faeces of rats after
administration of 1 nmol 2,3,7,8-TeBDD/kg body weight were 53% (oral
route), 43% (intratracheal route), and 10-20% (intravenous route). A
few days after oral application of 2,3,7,8-TeBDD (1 nmol/kg body
weight), about 20% of the dose administered was eliminated as parent
compound.

Data on retention and turnover are available for some PBDDs/
PBDFs. The relative body burden of 2,3,7,8-TeBDD (and other congeners)
in rats depends on the route of exposure and on the dose administered,
reflecting differences in absorption. Half-lives were calculated for
several PBDDs/PXDDs and PBDFs in various tissues and faeces of rats.
They ranged between 1 day (1,2,7,8-TeBDF from body) and 99 days
(2,3,4,7,8-PeBDF from liver). The estimated half-lives of 17, 18, and
58 days for 2,3,7,8-TeBDD in liver, faeces, and adipose tissue,
respectively, were similar to those reported for 2,3,7,8-TeCDD in
liver and faeces, but higher (by a factor of >2) than those reported
for 2,3,7,8-TeCDD in adipose tissue. Despite differences in early
retention, half-lives of 2,3,7,8-TeBDF and
2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TeCDF or TCDF) in liver were
comparable.

As with PCDDs/PCDFs, half-lives calculated for humans are much
longer than those for rats. There are estimations of 3-11 years (mean:
5.9 years) for 2,3,7,8-TeBDD and of 1-2 years (mean: 1.5 years) for
2,3,7,8-TeBDF. The persistence of these compounds in humans was also
seen in the case of a chemist who had synthesized 2,3,7,8-TeBDD and
2,3,7,8-TeCDD in 1956. Thirty-five years after exposure, markedly
elevated levels of 2,3,7,8-TeBDD were found in his blood.

1.6 Effects on laboratory mammals and in vitro test systems

Most studies were concerned with the toxicity of 2,3,7,8-TeBDD,
but some information was also available on other PBDDs/PBDFs and
PXDDs/PXDFs.

2,3,7,8-TeBDD caused typical 2,3,7,8-TeCDD-like effects,
including wasting syndrome, thymus atrophy, and liver toxicity.
Additionally, liver damage described as peliosis hepatis, which has
not been reported after exposure of rats to 2,3,7,8-TeCDD, was
observed. The pattern of lesions (lethality, histopathology, liver and

thymus weights) found in guinea-pigs after a single exposure and in
rats after short-term exposure to 2,3,7,8-TeBDF was similar to that of
2,3,7,8-TeCDF.

2,3,7,8-TeBDD interacts with the endocrine system. In rats,
dose-related changes in circulating thyroid hormones and impairment of
spermatogenic activity have been observed.

The oral LD₅₀ (28-day observation period) of 2,3,7,8-TeBDD in
Wistar rats was about 100 µg/kg body weight for females and about 300
µg/kg body weight for males. Oral LD₅₀ values for 2,3,7,8- TeCDD
obtained from other studies ranged between 22 and >3000 µg/kg body
weight. Equimolar doses of 2,3,7,8-TeBDF and 2,3,7,8-TeCDF resulted in
comparable mortality rates in guinea-pigs. For example, 100% mortality
was seen after treatment with both 2,3,7,8-TeBDF (0.03 µmol/kg body
weight, 15.8 µg/kg body weight) and 2,3,7,8-TeCDF (0.03 µmol/kg body
weight, 10 µg/kg body weight). Pre-peliotic lesions and changes in
thyroid hormones were seen in rats after a single dose of 100 µg
2,3,7,8-TeBDD/kg body weight.

In Wistar rats administered 2,3,7,8-TeBDD orally for 13 weeks,
evidence for decreased spermatogenic activity, defective and necrotic
spermatocytes, signs of severe peliosis hepatis, and changes in
circulating thyroid hormones and organ weights were observed. The
no-observed-adverse-effect level (NOAEL) was 0.01 µg/kg body weight
per day.

2,3,7,8-TeBDF administered orally to Sprague-Dawley rats for 4
weeks caused dose-dependent growth retardation and histopathological
changes in liver and thymus. The NOAEL was 1 µg/kg body weight per
day.

Developmental toxicity of some 2,3,7,8-substituted PBDDs/ PBDFs
occurred in mice at subcutaneous and oral doses that produced no
maternal toxicity and no fetal mortality. The lowest-observed-effect
levels (LOELs) (in µg/kg body weight) for hydronephrosis and cleft
palate after a single oral exposure of pregnant mice were,
respectively, as follows: 3 and 48 for 2,3,7,8-TeBDD, 25 and 200 for
2,3,7,8-TeBDF, 400 and 2400 for 2,3,4,7,8-PeBDF, and 500 and 3000-4000
for 1,2,3,7,8-PeBDF. Compared on a molar basis, 2,3,7,8-TeBDD and
2,3,7,8-TeCDD were almost equipotent in induction of hydronephrosis.
Compared on a weight basis, generally the brominated isomers were
slightly less potent than the chlorinated ones in induction of
hydronephrosis and cleft palate. However, 2,3,7,8-TeBDF was more
active than 2,3,7,8-TeCDF.

No information was found on the mutagenicity of PBDDs/PBDFs or
related end-points.

No long-term toxicity and carcinogenicity studies with PBDDs/
PBDFs were available. 2,3,7,8-TeBDD tested positive in a cell
transformation assay using murine peritoneal macrophages. However, the
transforming potency of 2,3,7,8-TeBDD was seven times less than that

of 2,3,7,8-TeCDD. Later, tumours developed in nude mice after
subcutaneous injection of the resulting established cell lines.

A series of several PBDDs and PXDDs (tetra and penta) given
intraperitoneally to immature male Wistar rats caused body weight
losses 14 days after injection. On the basis of molar ED₅₀ values,
the most toxic compounds tested were 2,3,7,8-TeBDD,
2-Br₁-3,7,8-Cl₃- DD, and 2,3-Br₂-7,8-Cl₂-DD (TBCDD), which are
substituted only in the four lateral positions. The relative potencies
of the other PBDDs examined followed the order 2,3,7,8- >
1,2,3,7,8- > 1,2,4,7,8- > 1,3,7,8-DD. In other experiments, there
were only slight differences in the ED₅₀ values (on a molar basis)
for body weight loss, thymic atrophy, and hepatic enzyme induction
between 2,3,7,8-TeCDD and 2,3,7,8-TeBDD.

Thymic atrophy and other signs of immunotoxicity (e.g.
haematological parameters, alterations of certain lymphocyte
subpopulations) were seen with several PBDDs/PXDDs and 2,3,7,8-TeBDF
in the rat and with 2,3,7,8-TeBDD and TBCDD in the marmoset monkey
(Callithrix jacchus). It was concluded that, on a molar basis, the
potency of 2,3,7,8-TeBDD was comparable to that of 2,3,7,8-TeCDD in
rats and monkeys. For example, a significant effect on certain
lymphocyte subpopulations in monkeys was found after a single
subcutaneous dose of 30 ng 2,3,7,8-TeBDD/kg body weight versus 10 ng
2,3,7,8-TeCDD/kg body weight. Effects on immunotoxicity after
perinatal exposure to PBDDs/PBDFs have not been investigated.

After subchronic dosing of either 2,3,7,8-TeBDD or 2,3,7,8-TeCDD
by oral gavage in mice, there was a dose-dependent increase in total
hepatic porphyrins.

After single oral doses of 2,3,7,8-TeBDD and 2,3,7,8-TeCDD,
reductions in concentration and total amount of vitamin A were
observed in the liver of rats, with 2,3,7,8-TeBDD being slightly less
potent than 2,3,7,8-TeCDD (on a molar basis).

2,3,7,8-TeBDD and 2,3,7,8-TeBDF produced hyperkeratosis in the
rabbit ear assay at a dose of 100 µg/rabbit, but not at 10 µg/rabbit.
A no-observed-effect level (NOEL) for 2,3,7,8-TeCDD was 0.01
µg/rabbit.

Several tetra- (Br₁Cl₃DDs, Br₂Cl₂DDs) and penta- (Br₁Cl₄DD)
halogenated congeners with 2,3,7,8-substitution were found to have an
antiestrogenic potency similar to that of 2,3,7,8-TeCDD, as examined
in cultures of human breast cancer cells.

In rats, 2,3,7-tribromodibenzo- p-dioxin (2,3,7-triBDD/TrBDD)
depressed the disappearance of ouabain from plasma, its excretion into
bile, and bile flow to a slightly lesser extent than 2,3,7,8-TeCDD.

PBDDs/PBDFs and PXDDs/PXDFs are potent inducers of certain
cytochrome P-450 (CYP)-dependent microsomal enzymes. ED₅₀ values of
0.8-1 nmol/kg body weight for CYP1A1 induction and about 0.2 nmol/kg

body weight for CYP1A2 induction in rat liver were estimated after
single oral doses of 2,3,7,8-TeBDD. CYP1A1 induction (arylhydrocarbon
hydroxylase [AHH] and/or ethoxyresorufin- O-deethylase [EROD]
induction) was observed in a variety of species and tissues
in vivo and in rat cell cultures in vitro. A lot of different
congeners were found to be active, as well as pyrolysates from certain
flame retardants. Generally, enzyme induction proceeded
dose-dependently at non-toxic concentrations, started soon after
exposure, and was long-lasting. It was measurable at exposures as low
as the pmol range. The induction potency varied over several orders of
magnitude for different congeners, depending on their chemical
structure. The most potent inducers were TCDD, TBDD, and TBCDD.
Compared (on a molar basis) with their chlorinated analogues, the
PBDDs and PXDDs had more or less similar potency. In contrast to TCDD,
whose relative induction potency was independent of the tissue
examined, TBDD was five times more potent at inducing EROD activity in
the liver than in skin and lung following subchronic exposure of mice.
The ranking order for induction of EROD activity in marmoset monkeys
was TCDD > 2,3,4,7,8-pentachlorodibenzofuran
(2,3,4,7,8-pentaCDF/PeCDF) > 2,3,4,7,8-PeBDF when enzyme activities
were compared with the hepatic concentrations. In vitro tests with
rat cell cultures resulted in similar molar EC₅₀ values of AHH and
EROD induction potencies between corresponding PXDFs and PCDFs.

PBDDs/PBDFs are believed to share a common mechanism of action
with PCDDs/PCDFs and other related halogenated aromatic hydrocarbons
(Ah). Binding to the cytosolic Ah receptor, which plays a central role
in mediating 2,3,7,8-TeCDD-like toxicity, was confirmed for several
PBDDs and PXDDs/PXDFs. Their receptor-binding affinities varied by
several orders of magnitude but were comparable to those of their
chlorinated analogues.

1.7 Effects on humans

There are no data on the exposure of humans to PBDDs/PBDFs or on
their effects on the health of the general population.

Two cases of acute health problems due to 2,3,7,8-TeBDD/ TeCDD
exposure have been reported, with symptoms including chloracne.

In another study, male personnel of a chemical plant with
documented exposure to PBDDs/PBDFs originating from the use of
brominated flame retardants (OBDE and DBDE) were subjected to
immunological and additional clinical laboratory tests. Although there
were indications of minor changes in immunological parameters, the
overall evaluation of their health status did not reveal an impact of
2,3,7,8-TeBDD/TeBDF body burden on the immune system.

There are no reports on cancer mortality caused by PBDDs/ PBDFs.

1.8 Effects on other organisms in the laboratory and field

There is only limited information on the effects of PBDDs/PBDFs
on microorganisms, plants, or invertebrate or vertebrate wildlife
species.

Using the rainbow trout (Oncorhynchus mykiss) sac fry early
life stage mortality bioassay, a series of PBDD/PBDF congeners were
tested and found to be active. This bioassay also demonstrated that
for both PBDDs and PBDFs, there was a decreased potency with increased
bromine substitution. Both 2,3,7,8-TeBDD and 2,3,7,8-TeBDF were more
potent than their chlorinated analogues.

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

2.1 Identity

PHDDs/PHDFs are almost planar tricyclic aromatic compounds. There
are eight positions on both the dibenzo- p-dioxin and the
dibenzofuran molecules where halogen substitution can occur. The
positions are numbered as shown in Fig. 1 for PBDDs and PBDFs.

Each series consists of eight homologous groups (groups of
congeners having the same number of bromine atoms), and in each group
there are different numbers of isomers (see Table 1). Theoretically,
75 PBDDs and 135 PBDFs are possible, as well as a large number of
mixed halogenated congeners -- 1550 PXDDs and 3050 PXDFs (Buser,
1987a). There are 7 2,3,7,8-substituted PBDDs and 10
2,3,7,8-substituted PBDFs (see Table 2), as well as 337 possible
2,3,7,8-substituted PXDDs and 647 possible 2,3,7,8-substituted PXDFs
(Ballschmiter & Bacher, 1996). PCDDs/PCDFs are discussed in a separate
Environmental Health Criteria monograph (WHO, 1989).

Because of the complexity of the analytical procedures (see
section 2.4), it has been possible to characterize only a small number
of PBDDs/PBDFs and PXDDs/PXDFs. Tables 3 and 4 show the Chemical
Abstracts Service (CAS) numbers that have been allocated to some of
these compounds.

2.2 Physical and chemical properties

2.2.1 Appearance, melting and boiling points, water solubility, vapour
pressure, octanol/water partition coefficient, and sorption coefficient

Experimental data on the physical and chemical properties of
PBDDs/PBDFs are scarce (see Table 5). In many cases, only predicted
values are available. It should be noted that for PCDDs, experimental
data are often lower than the calculated values (Shiu et al., 1988;
Fiedler & Schramm, 1990). This is also to be expected for the
brominated and for the mixed halogenated compounds (Fiedler & Schramm,
1990). Measured values for the aqueous solubility of PCDDs decrease
dramatically with increase in chlorine substitution and temperature
(Shiu et al., 1988).

PBDDs/PBDFs have higher molecular weights than their chlorinated
analogues, high melting points, and low water solubilities, but they
are generally soluble in fats, oils, and organic solvents (see Table
5). PBDDs/PBDFs have, like their chlorinated analogues, very low
vapour pressures, and at ambient temperatures they are mostly found
bound to particles. For the lower substituted compounds, PBDDs/PBDFs
have higher calculated p K_ow values than the chlorinated congeners
(Fiedler & Schramm, 1990) and are therefore more lipophilic.

Table 1. Number of isomers, elemental composition, and molecular weight for PBDDs/PBDFs

Compound Number of isomers Elemental Molecular
Total 2,3,7,8-Substituted composition weight

MoBDD 2 - C₁₂H₇O₂Br 263.1
DiBDD 10 - C₁₂H₆O₂Br₂ 342.0
TrBDD 14 - C₁₂H₅O₂Br₃ 420.9
TeBDD 22 1 C₁₂H₄O₂Br₄ 499.8
PeBDD 14 1 C₁₂H₃O₂Br₅ 578.7
HxBDD 10 3 C₁₂H₂O₂Br₆ 657.6
HpBDD 2 1 C₁₂HO₂Br₇ 736.5
OcBDD 1 1 C₁₂O₂Br₈ 815.4

MoBDF 4 - C₁₂H₇OBr 247.1
DiBDF 16 - C₁₂H₆OBr₂ 326.0
TrBDF 28 - C₁₂H₅OBr₃ 404.9
TeBDF 38 1 C₁₂H₄OBr₄ 483.8
PeBDF 28 2 C₁₂H₃OBr₅ 562.7
HxBDF 16 4 C₁₂H₂OBr₆ 641.6
HpBDF 4 2 C₁₂HOBr₇ 720.5
OcBDF 1 1 C₁₂OBr₈ 799.4

Table 2. PBDDs/PBDFs brominated at the
2,3,7,8-positions

PBDD congener^a PBDF congener^a

2,3,7,8-TeBDD* 2,3,7,8-TeBDF*
1,2,3,7,8-PeBDD* 1,2,3,7,8-PeBDF*
2,3,4,7,8-PeBDF*
1,2,3,4,7,8-HxBDD* 1,2,3,4,7,8-HxBDF
1,2,3,6,7,8-HxBDD* 1,2,3,6,7,8-HxBDF
1,2,3,7,8,9-HxBDD* 1,2,3,7,8,9-HxBDF
2,3,4,6,7,8-HxBDF
1,2,3,4,6,7,8-HpBDD 1,2,3,4,6,7,8-HpBDF
1,2,3,4,7,8,9-HpBDF
OcBDD OcBDF

^a The congeners marked with an asterisk (*)
are cited in the German Dioxin Directive (1994)
(see Appendix I).

2.2.2 Stability of PBDDs/PBDFs

2.2.2.1 Photolysis

In the presence of laboratory light or sunlight, photolysis
occurs at a more rapid rate for PBDDs/PBDFs than for PCDDs/PCDFs
(Buser, 1988; Chatkittikunwong & Creaser, 1994a; for details, see
section 4.2.1). This should be taken into consideration when analyses
of these compounds are carried out (see sections 2.4.1 and 4.2.1).

Photolysis on quartz surfaces under sunlight is a much slower
process than photolysis in organic solvents (Buser, 1988). PBDDs/
PBDFs adsorbed on incinerator soot particles remained relatively
stable and degraded only slowly during a 6-h period (Lutes et al.,
1990, 1992a,b). Studies of PBDDs in soil showed that for the same
congeners, the half-lives in this matrix are four times longer than in
solution (Chatkittikunwong & Creaser, 1994a).

Under conditions of ambient temperature and protection from
light, there is no appreciable (>1%) degradation of crystalline
PBDDs/ PBDFs and no significant change (0.6%, with the exception of
octaBDD [9.7%]) in standard solution (solvent: n-nonane)
concentrations over a period of 3 years (Re et al., 1995).

Table 3. CAS numbers for some PBDDs/PBDFs

PBDD congener^a CAS number PBDF congener^a CAS number

Br₁DD 103456-34-4 Br₁DF 103456-35-5
1-Br₁DD 105908-71-2 2-Br₁DF 86-76-0
2-Br₁DD 105906-36-3
Br₂DD 103456-37-7 Br₂DF 103456-40-2
1,6-Br₂DD 91371-14-1 2,7-Br₂DF 65489-80-7
2,7-Br₂DD 39073-07-9 2,8-Br₂DF 10016-52-1
2,8-Br₂DD 105836-96-2
Br₃DD 103456-38-8 Br₃DF 103456-41-3
1,2,8-Br₃DF 84761-81-9
2,3,8-Br₃DF 84761-82-0
Br₄DD 103456-39-9 Br₄DF 106340-44-7
1,2,3,4-Br₄DD 104549-41-9 1,2,7,8-Br₄DF 84761-80-8
2,3,7,8-Br₄DD 50585-41-6 2,3,7,8-Br₄DF 67733-57-7
Br₅DD 103456-36-6 Br₅DF 68795-14-2
1,2,3,7,8-Br₅DD 109333-34-8 1,2,3,7,8-Br₅DF 107555-93-1
2,3,4,6,7-Br₅DF 124388-77-8
2,3,4,7,8-Br5DF 131166-92-2
Br₆DD 103456-42-4 Br₆DF 103456-33-3
1,2,3,4,7,8-Br₆DD 110999-44-5 1,2,3,4,6,7-Br₆DF 124388-78-9
1,2,3,6,7,8-Br₆DD 110999-45-6 1,2,3,6,7,8-Br₆DF 107555-94-2
1,2,3,7,8,9-Br₆DD 110999-46-7
Br₇DD 103456-43-5 Br₇DF 62994-32-5
1,2,3,4,6,7,8-Br₇DF 107555-95-3
Br₈DD 2170-45-8 Br₈DF 103582-29-2

^a The homologue groups are underlined.

2.2.2.2 Thermolytic degradation of PBDDs/PBDFs

As discussed in chapter 3, the temperature of formation and
destruction of PBDDs/PBDFs depends on several conditions, such as
residence time, the presence/absence of oxygen, polymers, and
additives such as Sb₂O₃, as well as the efficiency of the apparatus
used for the thermal degradation. In laboratory experiments on the
thermolysis of polybrominated flame retardants (see section 3.4; Table
11), the PBDDs/PBDFs formed were destroyed at 800°C in an air
atmosphere after a 2.0-second residence time (Striebich et al., 1991).
PBDDs/PBDFs formed at 600°C from the thermolysis of plastics
containing DBDE or PBDE were no longer detectable at 800°C (Lahaniatis
et al., 1991). However, Thoma et al. (1987b) found that PBDDs/PBDFs
are still formed at 900°C. There is thus no definitive information on
the temperature needed to destroy PBDDs/PBDFs.

Table 4. CAS numbers for some PXDDs/PXDFs

PXDD congener^a CAS number PXDF congener^a CAS number

Br₁Cl₁DD 109007-09-02 Br₁Cl₁DF 109264-70-2
Br₁Cl₂DD 107227-59-8 Br_{1Cl₂DF 107227-60-1}
Br₁Cl₃DD 107227-75-8 Br₁Cl₃DF 107227-56-5
8-Br₁-2,3,4-Cl₃DF n.g.^b
Br₁Cl₄DD 109264-61-1 Br₁Cl₄DF 109302-36-5
1-Br₁-2,3,7,8-Cl₄DF 104549-43-1
4-Br₁-2,3,7,8-Cl₄DF 115656-08-1
Br₁Cl₅DD 109264-65-5 Br₁Cl₅DF 107103-81-1
Br₁Cl₆DD 109264-67-7 Br₁Cl₆DF 107207-47-6
Br₁Cl₇DD 109264-69-9 Br₁Cl₇DF 109302-40-1

Br₂Cl₁DD 107227-58-7 Br₂Cl₁DF 107227-57-6
Br₂Cl₂DD 107227-74-7 Br₂Cl₂DF 107227-55-4
Br₂Cl₃DD 109031-99-4 Br₂Cl₃DF 107227-53-2
Br₂Cl₄DD 109264-62-2 Br₂Cl₄DF 107207-48-7
Br₂Cl₅DD 109264-66-6 Br₂Cl₅DF 107207-45-4
Br₂Cl₆DD 109264-68-8 Br₂Cl₆DF 109302-39-8

Br₃Cl₁DD n.g.^b Br₃Cl₁DF 107227-54-3
Br₃Cl₂DD n.g.^b Br₃Cl₂DF 107227-52-1
Br₃Cl₃DD n.g.^b Br₃Cl₃DF 107207-46-5
Br₃Cl₄DD n.g.^b Br₃Cl₄DF 107207-42-1
Br₃Cl₅DD n.g.^b Br₃Cl₅DF n.g.^b

Br₄Cl₁DD n.g.^b Br₄Cl₁DF 107227-51-0
Br₄Cl₂DD n.g.^b Br₄Cl₂DF 107207-44-3
1,2,3,4-Br₄-7,8-Cl₂DD 134974-39-3
Br₄Cl₃DD n.g.^b Br₄Cl₃DF 107207-41-0
Br₄Cl₄DD n.g.^b Br₄Cl₄DF n.g.^b
1,2,3,4-Br₄-6,7,8,9-Cl₄DD 124728-12-7

Br₅Cl_xDD n.g.^b Br₅Cl₁DF 107207-49-8
other Br₅Cl_xDF n.g.^b

Br₆Cl₁DD 107207-38-8 Br₆Cl₁DF n.g.^b
Br₆Cl₂DD n.g.^b Br₆Cl₂DF 107207-36-3
1,2,4,6,7,9-Br₆-3,8-Cl₂DD 2170-44-7

Br₇Cl₁DD n.g.^b Br₇Cl₁DF 107207-37-4

^a The homologue groups are underlined.
^b n.g. = CAS numbers not found (probably not yet allocated).

Table 5. Physical and chemical properties of some PBDDs/PBDFs

Compound Appearance Melting point Boiling point Water Vapour Octanol/water Sorption
(°C) (observed) (°C) solubility pressure partition coefficient
(predicted) [log S] [log P] coefficient [log K_oc]
(mol/litre) (Pa at 25°C) [log K_ow] (mol/litre)
(predicted) (predicted) (predicted) (predicted)

PBDDs
1-MoBDD white needles 104-106^a 338.2^b 3.5 × 10^-3b
2-MoBDD n.g.^c 93-94.5^a 338.2^b -6.12^d 4.0 × 10^-3b 5.62^d 4.39^d
(90-92)^a
1,6-DiBDD 207^e 375^b 1.5 × 10^-4b
2,3-DiBDD n.g.^c 157.2-158^f 375^b -6.90^d 1.6 × 10^-4b 6.25^d 4.74^d
2,7-DiBDD 174-176^a 375^b 1.5 × 10^-4b
193-194^e
2,8-DiBDD 149.5-151^a 375^b 1.7 × 10^-4b
(145-150)^a
3,7-DiBDD -7.24^d 6.53^d 4.89^d
-7.99^d 7.14^d 5.22^d
1,2,3,4-TeBDD 6 × 10^-7g
2,3,7,8-TeBDD white granules 334-336^a,f 438.3^b -8.72^d 6.4 × 10^-7b 7.74^d 5.54^d
6.50^h
7.73ⁱ

1,2,3,7,8-PeBDD -9.45^d 8.32^d 5.87^d
1,2,3,4,6,7, -10.89^d 9.50^d 6.50^d
8-HpBDD
OcBDD 376^j 523.2^b -11.69^d 4.1 × 10^-11b 10.08^d 6.82^d
9.3 × 10^-16g
PBDFs

monoBDF 2.89-3.26^k
2-MoBDF -5.42^d 5.05^d 4.08^d
diBDF 4.35-4.46^k 5.58-6.09^k
2,7-DiBDF -6.25^d 5.95^d 4.47^d
triBDF 5.36-5.47^k 6.49-6.79^k

Table 5. (Continued)

1,2,8-TrBDF + colourless 144-148^l
2,3,8-TrBDF prisms^l
2,3,7-TrBDF -7.26^d 6.55^d 4.90^d
tetraBDF 6.35-6.41^k 7.72-8.72^k
1,2,7,8-TeBDF colourless needles^l 240.5-242^l 6.20^h
2,3,7,8-TeBDF colourless needles^l 301-302^l -7.99^d 7.14^d 5.22^d
5.98^h
2,3,4,6-TeBDF -7.99^d 7.14^d 5.22^d
pentaBDF 7.25-7.45^k
1,2,3,7,8-PeBDF 7.04^h
7.56ⁱ
2,3,4,7,8-PeBDF -8.71^d 7.73^d 5.54^d
hexaBDF 8.34^k
2,3,4,6,7, -9.43^d 8.31^d 5.86^d
8-HxBDF
1,2,3,4,6,7, 9 × 10^-11g
8-HpBDF

^a From Gilman & Dietrich (1957). Melting points in parentheses are values from other sources
reported by these authors.
^b From Rordorf (1987).
^c n.g. = not given.
^d Predicted; from Fiedler & Schramm (1990). Sorption coefficient [log Koc] = distribution
coefficient between compound adsorbed to soil organic carbon and the compound in solution.
^e From Tomita et al. (1959)
^f From Kende & Wade (1973).
^g From Rordorf et al. (1990).
^h From Jackson et al. (1993), estimated from measured reverse-phase high-performance liquid
chromatography (HPLC) retention times.

Table 5. (Continued)

ⁱ From Jackson et al. (1993), calculated.
^j From Denivelle et al. (1960).
^k From Watanabe & Tatsukawa (1990).
^l From Tashiro & Yoshiya (1982).

2.2.3 Chemical reactions

Aromatic carbon-bromine bonds are generally weaker than similar
carbon-chlorine bonds, and, consequently, bromine can be substituted
more easily. In general, the reductive substitution of halogens in
aromatic structures becomes easier as the halogen atoms' size
increases (Wania & Lenoir, 1990).

In the presence of excess chlorine, bromine can be substituted by
chlorine to give PXDDs/PXDFs -- for example, under conditions such as
those present in municipal incinerators (Wilken et al., 1990; Luijk et
al., 1992a).

Wania & Lenoir (1990) investigated the effect of heating
1,2,3,4-TeBDD (20 µg) in the presence of copper (1 g) at 100, 120,
150, or 210°C for a duration of 30 seconds to 1 h. With increasing
heating time, the spectrum of PBDD shifted from tetraBDD to lower
brominated congeners, and the sum of the quantities decreased. The
reaction rate increased with increasing temperature. At 210°C for 30
min, all PBDDs had disappeared, but the dibenzo- p-dioxin ring
structure remained intact.

In a further experiment, it was shown that the presence of water
(10 or 100 µg/litre) considerably increased the yield of debrominated
products.

On heating monoBDD and 1 g copper to 150°C, the debrominated
product dibenzo- p-dioxin and dimers of this compound were
identified. On heating hexaBDD and octaBDD to 150°C in the presence of
copper, it was found that appreciable quantities of the original
compounds could still be detected after 1 h. The reaction was
considerably slower than in the comparable experiment with tetraBDD.

The debromination reactions proceed faster than the respective
dechlorination reactions with PCDDs (Hagenmaier et al., 1987).

2.3 Conversion factors

At 25°C and 101.3 kPa, conversion factors for converting airborne
concentrations from ppm to mg/m³ for a particular PBDD/ PBDF congener
can be calculated from the relative molecular mass (RMM):

1 ppm = RMM/24.45 mg/m³
1 mg/m³ = 24.45/RMM ppm

For example, for monoBDF, 1 ppm = 247.1/24.45 = 10.1 mg/m³.
Similarly, 1 mg/m³ = 0.099 ppm.

2.4 Analytical methods

2.4.1 General aspects

Some PBDD/PBDF congeners are highly toxic (see chapter 7). Using
the principles of Good Laboratory Practice, great precautions should
be taken in handling the samples. Additionally, precautions must be
taken owing to the photochemical instability of the brominated and
mixed brominated/chlorinated congeners (see also sections 2.2.2.1 and
4.2.1). The use of amber-coloured glassware and filters on lamps and
windows is mandatory.

Sampling, sample treatment (extraction and clean-up), and
analysis for PBDDs/PBDFs and PXDDs/PXDFs follow largely the methods
and techniques currently used for PCDDs/PCDFs (Donnelly et al.,
1989a,b, 1990; US EPA, 1990, 1992 [Methods 1613 and 8290]; Maier et
al., 1994; Ballschmiter & Bacher, 1996). The large number of isomers
in some homologous groups (see Table 1) makes the separation and
quantification of individual congeners difficult. Using highly
selective, specific, and sensitive analytical methods,
2,3,7,8-substituted PBDDs/PBDFs can be detected, although co-elution
with other isomers cannot be excluded.

Accurate identification of specific congeners is limited by the
small number of reference standards available. The large number of
PXDDs/PXDFs (see section 2.1) makes it impossible to identify and
quantify individual congeners. Homologue groups, however, can be
analysed semi-quantitatively. Major steps in the analytical procedures
are as follows:

- spiking of the homologous sample with labelled standards
- use of matrix-specific extraction procedures (pretreatment of the
sample before extraction where necessary)
- clean-up by column chromatography, liquid-liquid extraction, HPLC
- concentration of the eluate (addition of a high-boiling solvent
as a keeper where necessary); addition of a recovery standard
- analysis by GC/MS.

Many of the analytical methods for PCDDs/PCDFs have been
validated in the past decade in interlaboratory studies organized,
among others, by: the World Health Organization (WHO) for biological
samples (WHO/EURO, 1989, 1991; Stephens et al., 1992; WHO/ECEH, 1996);
the European Community Bureau of Reference for environmental samples,
including fly ash (Maier et al., 1994), and for milk powder (Schimmel
et al., 1994; Tuinstra et al., 1996); and the European Committee for
Standardization for emissions by stationary sources (Bröker, 1996). To
avoid systematic errors in the individual steps from sampling to
analysis, recoveries must be controlled by the addition of appropriate
stable isotope labelled standards before extraction of the sample,
clean-up, and final quantification.

2.4.2 Sampling and extraction

The sampling procedures recommended for PCDDs/PCDFs (WHO, 1989
and citations in second paragraph of section 2.4.1) also apply for the
brominated congeners.

2.4.2.1 Ambient air, airborne dust, automobile exhaust, flue gas, and
products of thermolysis

Experience from PCDD/PCDF analysis has shown critical or weak
points in current gas sampling (ambient air, indoor air, exhaust gas)
techniques. Requirements are as follows:

- representativeness of samples; special attention must be given to
isokinetic sampling of particles in emission samples
- stability of the sample on the sampling medium during the
sampling period; the filter should be kept below 120°C and
protected from light
- recovery of the analytes from the sampling train (as checked by
appropriate spiked standards)
- use of clean equipment to avoid contamination of the sample (as
checked by appropriate blanks)
- complete trapping of gas and particle phases (aerosols) to avoid
sample losses.

Quartz fibre filters with polyurethane foam plugs have been used
to sample ambient air up to 1000 m³ (Wagel et al., 1989; Päpke et
al., 1990; Harless et al., 1992; Watanabe et al., 1992). (Note: There
may be interferences from brominated organic aromatic flame retardants
in polyurethane foam.)

Haglund et al. (1988) described a method to collect both the
particulate phase (using a Teflon-coated filter) and the gas phase
(cryotechnique) in vehicle exhaust.

Hutzinger et al. (1990) used the so-called Grimmer apparatus to
sample automobile exhaust: the sampling train consists of a large
glass condenser and a non-impregnated fibreglass filter. Typically, 50
m³ of automobile exhaust were taken per sample; the temperature at
the muffler outlet was kept below 50°C. The experiments were carried
out as stationary motor tests. The total emissions of the motor were
sucked through the sampling train by a pressure-controlled blower.

Emissions from a laboratory furnace experiment were collected by
a sampling train, including a high-efficiency quartz fibre filter (to
collect organic-laden particulate material) and an XAD-2 resin (to
adsorb semivolatile organic compounds) (Riggs et al., 1992).

Thermolytic products have been collected as condensate in a
quartz-wool-filled condenser tube (Neupert et al., 1989b).

2.4.2.2 Water and aqueous samples

Analysis of water samples should follow a different approach. If
the samples are free of particles, a normal liquid-liquid extraction
is sufficient. If, however, the samples contain particles, both the
particles and the water phase should be extracted separately -- the
solids by methods recommended for solids, the water phase as described
above.

2.4.2.3 Environmental samples: soil, sediment, and sewage sludge

For environmental samples, problems arise in obtaining a
representative sample. For soil sampling, a method was described by
Fortunati et al. (1994).

Prior to the extraction, appropriate measures should be taken to
ensure that PHDDs/PHDFs in the sample material are fully accessible to
the extraction solvent. In a number of applications, this includes a
digestion of the sample (solids) and/or the complete removal of water
(wet solid samples) prior to extraction clean-up; a chemical
destruction of non-persistent chemicals can be useful by incubating
the sample in neat sulfuric acid (H₂SO₄). PHDDs/PHDFs are shown to
be stable. Treatment with (strong) bases should be avoided, as
PHDDs/PHDFs may degrade.

For the study of sewage samples, Hagenmaier et al. (1992) dried,
powdered, and extracted the samples with toluene for 18 h. After
concentration, the extracts were treated with concentrated sulfuric
acid.

Proven digestion and water removal methods are treatment with
hydrochloric acid (10% HCl) and Dean Stark collector (US EPA, 1990;
Rappe et al., 1996), respectively. Sediments should be treated with
copper powder to eliminate sulfur (Kjeller et al., 1993).

2.4.2.4 Flame retardants, polymers, fly ash samples, dust, soot, and
fire residues

In general, the analysis of plastics is performed by dissolving
the polymer in a suitable solvent. Non-dissolvable plastics should be
powdered and Soxhlet-extracted.

Dibromomethane was used to dissolve samples of PBDE (Tondeur et
al., 1990). Ranken et al. (1994) noted that this solvent must first be
specially purified before use to remove the colour, which caused
quantitative interferences in the mass spectrometer. TBBPA can be
dissolved in methanol (Tondeur et al., 1990; Ranken et al., 1994).

PBT resins (extruded beads/powder) were extracted best with
1,1,1-trichloroethane/phenol followed by water partitioning of phenol;
powdered high-impact polystyrene (HIPS) samples by toluene/reflux; and
powdered ABS samples by dichloromethane (Donnelly et al., 1989a).

Kieper (1996) used toluene for Soxhlet extraction from samples of
flame-retarded polymers: DBDE (with polystyrene/polystyrenebutadiene),
1,2-bis(tribromophenoxy)ethane (with polystyrene), TBBPA-carbonate
oligomer (with PBT), dibromostyrene, and tribromostyrene (both with
polyamide 66).

Samples of burnt plastic, PBT material, ash/slag, and soil were
Soxhlet-extracted with dichloromethane (Neupert & Pump, 1992). Clausen
et al. (1987) used Soxhlet extraction with hexane. ABS was extracted
under reflux with methylene chloride (Donnelly et al., 1990).

Dry fly ash was treated with 10% HCl, dried, and neutralized.
After further drying, the sample was Soxhlet-extracted with toluene
(Hosseinpour et al., 1989). Similar procedures were used by Tong et
al. (1991) and Huang et al. (1992a,b).

PBDDs/PBDFs from dust samples and smoke condensate were
Soxhlet-extracted with toluene (UBA, 1992; Funcke et al., 1995).
Samples from fire residues were ground and extracted with toluene;
wipe samples of soot were extracted with hexane (Harms et al., 1995).

2.4.2.5 Biological matrices: human milk, blood/plasma, tissues, and
fish samples

For biological samples, most appropriate extraction methods are
those giving the highest yields (or recovery) for the lipids in the
sample (i.e. milk, blood, tissue).

Neupert et al. (1989a,b) quantified PBDDs/PBDFs in rat liver,
adipose tissues, and faeces. After homogenization with sodium sulfate,
extraction was performed on a multiple-layer column using
dichloromethane/hexane.

Fish samples were ground with sodium sulfate and homogenized.
Methanol and sodium oxalate were added to milk samples (De Jong et
al., 1992). Diethyl ether and hexane were used to extract PHDDs/ PHDFs
from the fat fraction of the milk and fish samples.

For PBDD/PBDF determination, samples of human adipose tissue were
homogenized, extracted with dichloromethane, dried with sodium
sulfate, and solvent-exchanged into hexane (Cramer et al., 1990a).
This method was also used by Zober et al. (1992).

Fat removal can be performed utilizing a semipermeable membrane
technique (Bergqvist et al., 1993), which enables larger amounts of
fat (sample size up to 200 g) to be eliminated from the sample matrix
(>95%) and improved detection limits.

Lyophilization has been used successfully in the analysis of TBDD
in biological matrices such as rat livers or marmoset monkey tissues
(Schulz-Schalge et al., 1991a,b; Schulz et al., 1993; Nagao et al.,
1995/96).

2.4.3 Sample clean-up

Sample clean-up is carried out to remove those materials that
might otherwise interfere with the analysis. A variety of liquid
chromatography separations have been used, including silica, florisil,
alumina, and various combinations of these columns. Usually an
acid/base wash followed by alumina column chromatography is used to
remove the bulk of interferences, and carbon column chromatography is
used to remove residual interferences (Donnelly et al., 1986, 1987,
1989b).

Where PBDEs are likely contaminants, a modification of separation
techniques is necessary. Alumina columns are ineffective in separating
PBDFs from PBDEs. Carbon columns were found to be more effective, but
the higher brominated PBDFs could be removed from the column only by
back-flushing with an aromatic solvent (Donnelly et al., 1987; Hileman
et al., 1989). Bonilla et al. (1990) introduced an HPLC step to the
clean-up procedure. The sample was passed through an AX21 carbon
column. The column was washed in the forward direction with
dichloromethane/cyclohexane and dichloromethane/methanol/benzene and
back-flushed with toluene. This procedure decreased the PBDE
concentration in the final sample by six orders of magnitude.

Depending on the aim of the analysis (general surveying or
specific search and quantification of 2,3,7,8-substituted congeners),
a number of ¹³C standards are required to be added at several stages
during sampling and analysis.

In the WHO interlaboratory calibration study for the analysis of
PCDDs/PCDFs in human blood and milk, the basic clean-up/ separation
methods used by some laboratories were activated carbon as the primary
PCDD/PCDF isolation step followed by alumina; the remaining
laboratories used other procedures, mostly H₂SO₄ followed by
alumina. Nearly all methods used a step involving some type of carbon
chromatography (Stephens et al., 1992).

2.4.4 Separation

GC is used for the separation of PBDDs/PBDFs. PBDDs/PBDFs have
much higher retention times and elution temperatures (30-40°C higher)
than their chlorinated analogues (Buser, 1991). The higher brominated
congeners have extremely long retention times, so non-polar (SE 54),
medium-length (up to 25-m) columns are generally used. Such a column
is suitable for separating the PBDD and PBDF homologues. Elution
temperatures on a 25-m SE 54 high-resolution gas chromatography (HRGC)
column range from 184-188°C for monoBDDs/BDFs to 260-273°C for
pentaBDDs/BDFs. Hexa-, hepta-, and octa-homologues elute during the
isothermal phase at 280°C (Buser, 1986a, 1991). Cross-linked columns
allow higher temperatures, reducing analysis times (Hutzinger et al.,
1990). Table 6 gives retention indices (RIs) of some PBDDs/PBDFs as
well as PBDEs, which are possible contaminants (Donnelly et al.,
1987). A 30-m DB-5 or DB-5MS fused capillary column has been found to

be quite useful for the GC/MS analysis of tetra- through
hepta-substituted PBDDs/PBDFs (Ranken et al., 1994).

Table 6. Retention indices (RIs) of PBDDs,
PBDFs, and PBDEs^a,b

Congener RI

PBDDs
2-MoBDD 1868
2,8-DiBDD 2174
1,3,7-TrBDD 2423
2,3,7-TrBDD 2475
2,3,7,8-TeBDD 2800
1,2,7,8-TeBDD 2811
1,2,4,7,8-PeBDD 3072
1,2,3,7,8-PeBDD 3145
1,2,3,4,7,8-HxBDD 3412
1,2,3,6,7,8-HxBDD 3475
1,2,3,7,8,9-HxBDD 3798
1,2,3,4,6,7,8-HpBDD 3763
OcBDD 4219

PBDFs
2-MoBDF 1834
2,8-DiBDF 2133
1,2,8-TrBDF 2416
2,3,8-TrBDF 2433
1,2,7,8-TeBDF 2740
2,3,7,8-TeBDF 2791
1,2,3,7,8-PeBDF 3103
1,2,3,6,7,8-HxBDF 3479
1,2,3,4,6,7,8-HpBDF 3806
OcBDF 4231

PBDEs
HexaBDE 2888
HexaBDE 3004
HexaBDE 3015
HexaBDE 3030
HexaBDE 3051
HexaBDE 3095
HexaBDE 3286
HexaBDE 3314
HexaBDE 3369
HexaBDE 3411
OctaBDE 3525
OctaBDE 3577
OctaBDE 3601
OctaBDE 3627

Table 6. (Continued)

Congener RI

OctaBDE 3654
OctaBDE 3737
OctaBDE 3786
NonaBDE 3951
NonaBDE 4003
DecaBDE 4310

^a From Donnelly et al. (1987).
^b Chromatographic conditions:
30 m x 0.32 mm DB-5 GC column;
He carrier gas at ca. 7 psi head
pressure; temperature programmed
from 10 min at 170-320 °C at
8 °C/min.

The elution of PCDDs/PCDFs and PBDDs/PBDFs occurs in the order of
the molecular weights. PXDDs/PXDFs elute between the corresponding
chloro- and bromo-analogues (Buser, 1987a). However, mixed congeners
containing bromine elute earlier than expected on a molecular weight
basis, relative to the chloro-compounds (e.g. BrCl₅ before Cl₇)
(Buser, 1991). (For isomer-specific analysis, columns of different
polarity should be used.)

Owing to the lack of PBDD/PBDF (and PXDD/PXDF) standards, it has
not been possible to identify all congeners. Instead, a combination of
MS and GC RI identification has to be used for the analysis of
2,3,7,8-substituted PBDDs/PBDFs, PCDDs/PCDFs, and PXDDs/ PXDFs. An RI
model has been developed to predict the GC retention times for 1700 of
these compounds (Donnelly & Sovocool, 1991; Donnelly et al., 1991a,b).

2.4.5 Detection, quantification, and confirmation of PBDDs/PBDFs
by MS techniques

Detection, quantification, and confirmation are usually performed
by MS, as only this technique shows sufficient selectivity to
distinguish PBDDs/PBDFs from other halogenated compounds (e.g. PBDEs)
that are present in the sample. MS allows the determination of the
number and type of halogens present from characteristic isotope
distribution patterns,