United States
Environmental Protection
Agency
Office of Environmental
Processes and Effects Research
Washington DC 20460
Research and Development
EPA/600/S9-86/004 June 1986
f/EPA Project Summary
Report on the Research
Planning Workshop on
Bioavailability of
Dioxins—September 1984
Research on the class of compounds
called dioxins began several decades
ago, but the research activity increased
substantially in the 1960's and 1970's,
when the complex problem of dioxin
contamination received national and in-
ternational attention. Although consid-
erable research has continued in this
field, there are still voids in scientific
knowledge, among them an under-
standing of the bioavailability of diox-
ins, that need to be identified to evalu-
ate more accurately human and
environmental risks associated with
these chemicals.
The EPA Office of Research and De-
velopment sponsored the Research
Planning Workshop on the Bioavailabil-
ity of Dioxins, September 9-12, 1984,
that brought together scientists and
managers in various aspects of dioxin
work from government agencies,
academia, and industry. About ninety
researchers focused their attention dur-
ing the four-day meeting on identifying
the most obvious gaps in knowledge
and the consequent research needs,
evaluating the ongoing research on the
bioavailability of chlorinated dioxins
and related chemicals and developing a
research plan.
Workshop participants were orga-
nized into three groups that addressed
the topics: environmental processes in
bioavailability, bioavailability to
ecosystems, and bioavailability to hu-
mans. The Environmental Processes in
Bioavailabilrty Group focused on defin-
ing various environmental processes
controlling the bioavailability of TCDD
in the biosphere. Transformation proc-
esses and bioavailability assessments
were also discussed in this group. The
Bioavailability in Ecosystems Group
evaluated the factors relevant to the
bioavailabilrty of dioxins in aquatic and
terrestrial ecosystems and the poten-
tial impact of these chemicals on
ecosystems. Ecosystem processes
were identified, particular species and
communities that are potentially im-
pacted by dioxins were addressed, and
the role of food chains and the food
web in human exposure and risks was
discussed. The Bioavailability to Hu-
mans Group evaluated factors such as
the bioavailabilrty of TCDD from envi-
ronmental matrices, the host factors af-
fecting bioavailability, in vivo
bioavailability, routes of exposure,
toxic human effects, interspecies differ-
ences, and extrapolation from other an-
imals to humans.
This Project Summary was devel-
oped by EPA's Office of Environmental
Processes and Effects Research, Wash-
ington, DC, to announce key findings of
the research project that is fully docu-
mented in a separate report of the same
title (see Project Report ordering infor-
mation at back).
Introduction and Background
The class of chemicals polychlori-
nated dibenzo dioxins, commonly
known as dioxins, has attracted great
attention and raised controversies dur-
ing recent years. In the United States,
issues about dioxins surfaced during
the 1960's, when 2,3,7,8-tetrachloro-
dibenzo-p-dioxin (2,3,7,8-TCDD) was
found to be a contaminant in the com-
monly used herbicide 2,4,5-T (2,4,5-
trichlorophenoxy-acetic acid). The high
toxicity and persistence of 2,3,7,8-TCDD
in the environment represent the pri-
mary characteristics of dioxins that
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pose risks to human health and the en-
vironment. Because the dioxins repre-
sent a large chemical class and most
attention to date has been focused on
the isomer 2,3,7,8-TCDD, special termi-
nology is used in this document to ad-
dress these chemicals: the term TCDD
refers to 2,3,7,8-TCDD; the term dioxins
refers to other isomers.
Since the 1960's, several incidents
have focused attention on the contami-
nation problem: the human and envi-
ronmental exposure to dioxins as a re-
sult of a chemical plant accident in
Seveso, Italy; the identification of diox-
ins at several hazardous waste sites in
the states of Missouri, New Jersey, New
York, and Arkansas; and the occurrence
of dioxins in fish samples in the states
of Michigan and Wisconsin. Dioxins are
also associated with combustion proc-
esses and have been found in municipal
incinerator fly ash.
Central to the complex issues of expo-
sure and risk assessment is the evalua-
tion of the bioavailability of dioxins. The
term bioavailability has not been clearly
defined, and the subject remains poorly
understood; It involves understanding
factors related to the uptake, release,
metabolism, or bioaccumulation of
dioxins by living organisms. Recent
findings at the National Institute of Envi-
ronmental Health Sciences indicate that
TCDD bioavailability to laboratory ani-
mals varies substantially. To under-
stand bioavailability, the environmental
processes that may influence it in
ecosystems and humans must be char-
acterized. Identification and quantifica-
tion of TCDD and other dioxins in envi-
ronmental and biological matrices also
require major attention. While most re-
search data deal with TCDD, the toxic
effects and environmental risks associ-
ated with other dioxins also need evalu-
ation.
Summary of the Workshop
Report
Each group of participants at the
workshop addressed specific areas re-
garding bioavailability, within the broad
range of dioxin research, and identified
areas for study in their final summary
reports. However, the definition and
concept of bioavailability varied among
the three groups. One group addressed
dioxins in general, whereas the other
two groups worked on the isomer
2,3,7,8-TCDD. The final report details
the deliberation of the three panels as
summarized below.
Environmental Processes in
Bioavailability
The group dealing with the environ-
mental processes in the bioavailability
of TCDD evaluated the state-of-the-art
in analytical methods, physical and
chemical properties, transport and
transformation processes, and expo-
sure modeling. The group addressed
the basic scientific understanding re-
quired for valid estimation of exposure,
bioavailability, and risk. The group iden-
tified major gaps in knowledge and pri-
oritized the research needs in these
areas. In ranking the research objec-
tives, the group considered both short-
and long-term needs.
Photochemical Processes
Available information indicates that
photolysis offers the most promising
environmental process for degrading
TCDD. Therefore, the highest research
priority was assigned to better charac-
terization of the rates and extent of di-
rect and indirect photolysis in air, on
surfaces, and in water.
Physical and Chemical
Properties
The second research priority con-
cerns the expansion of the data base
covering physical and chemical proper-
ties of TCDD and related compounds.
The use of structure-activity relation-
ships, based on thermodynamic laws,
to predict physical and chemical proper-
ties possibly offers a cost-effective alter-
native to numerous laboratory determi-
nations.
Sorption/Desorption/
Volatilization
To understand better the dynamics of
TCDD movement in all environmental
media, specific studies of sorption/de-
sorption phenomena are needed. These
include, the effects of organic content of
soils and sediments on the sorption/de-
sorption of TCDD from the saturated
and unsaturated zones and the effects
of particulates on TCDD in the atmos-
phere.
Chemical Transformations
The chemical transformations of
TCDD have not been characterized. A
complete definition of the transforma-
tion processes will contribute to the
understanding of transport and provide
specific chemical reactions that may de-
grade TCDD. The ability of TCDD to
undergo oxidation/reduction, acid/base
hydrolysis, nucleophilic displacement,
and metal chelation reactions needs to
be determined.
Biological Processes
The use of biodegradation as a cost-
effective procedure for TCDD degrada-
tion is a long-term, high-priority re-
search need. Because the gene action
for TCDD metabolism has been demon-
strated in higher organisms, the
employment of recombinant DNA tech-
nology to insert the gene(s) into mi-
croorganisms to degrade TCDD will
benefit future cleanup operations and
reduce the environmental and human
risk.
Intermedia Transport
Although the rates of certain interme-
dia transfers can be predicted, suitable
measurement techniques are not avail-
able to validate the predictions. The
transport and intermedia transfer of
most TCDD requires further investiga-
tion. The movement of TCDD-
contaminated particles appears to be a
critical link in the bioavailability of
TCDD.
Modeling
Currently available mathematical ex-
posure models are applicable to predict
the exposure concentrations of TCDD in
various environmental media when the
various equilibrium and rate coeffi-
cients have been determined. However,
research will be required to apply and
test the media and multimedia models
to determine their applicability preci-
sion, and accuracy.
Surrogate Parameters for
Combustion
The production of dioxins and furans
from municipal incinerators is well doc-
umented. Identification and measure-
ment of these chemical species are
costly. To control effectively the com-
bustion process so that the release of
these compounds is eliminated, new
surrogate parameters for process con-
trol are needed.
Need for Sufficient Supplies of
TCDD for Research
An adequate supply of TCDD and lab-
oratory standards for all possible iso-
mers of dioxins and furans is not readily
available. These chemicals are required
for quality assurance and quality con-
trol and to facilitate investigations of
dioxin and furan distribution in the envi-
ronment. A toxicological evaluation of
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dioxins and furans cannot be conducted
without the appropriate laboratory
standards.
Bioavailability in Ecosystems
To gain a better understanding of the
pathways to humans and effects on the
ecosystem, the fate and transport of
dioxin in the environment must be de-
termined. These include: the bioavail-
ability of dioxin to biota and the influ-
ence of organisms on the transport of
dioxins within and across systems. Also
of interest are rates of exchange, of
dioxin uptake by plants from soil, and
the transport of the chemical through a
series of organisms in the human food
web to people themselves.
To clarify such interactions, results of
group discussion are presented in a sec-
tion on a conceptual framework for ex-
changes of dioxin among ecosystem
components, followed by sections on
aquatic and terrestrial ecosystems con-
cerning fate, transport, effects on biota
(species and processes), and pathways
to humans.
In these sections, three sets of topics
were considered: 1) identification of
ecosystem processes that a) are in-
volved in routes, rates, and reservoirs of
dioxins in aquatic and terrestrial
ecosystems; b) are particularly suscep-
tible to effects of dioxin contamination;
or c) are involved in biological decon-
tamination processes; 2) identification
of particular species and economically
important communities that are im-
pacted or potentially impacted by diox-
ins; and 3) identification of the role of
food chains and webs in human expo-
sure and risk.
Research Needs
Data on the impact of dioxins at the
ecosystem level are essentially nonexis-
tent, and relatively few data are avail-
able describing the effects of these
chemicals on single species. Therefore,
many research needs were identified by
group participants; the following were
considered the highest priority:
• Develop the capability to predict
dioxin levels in tissues (particularly in
organisms that constitute human
food chains) as a function of environ-
mental conditions; develop toxicity
data for understanding the mecha-
nisms of toxicity and the factors re-
sponsible for differences in sensitivi-
ties among species.
• Measure the concentration of dioxins
over time in organisms as a function
of dose in food, water, and other
sources for model development. Use
microcosms for model verification.
• Conduct a full-scale ecological study
at a highly contaminated site. Include
field studies of fate, chronic effects,
and ecological processes, with sup-
porting laboratory studies.
• Evaluate the chemical and biological
characteristics of residue from exper-
imental incineration projects and in-
corporate results in risk assessment.
In addition to these research needs,
there is a need to improve risk assess-
ment capability and to evaluate the un-
certainties resulting from conflicting
data, unexpected indirect effects, and
laboratory-to-field extrapolations.
Bioavailability to Humans
Risks may be inaccurately estimated
in the absence of knowledge about fac-
tors determining bioavailability, even
when exposure is relatively well de-
fined. Clearly, matrix and route effects
are likely to be significant. However, hu-
man responses and risk are also influ-
enced by exposure and by differences in
the sensitivity of target sites of action.
To consider bioavailability adequately,
exposure and toxic response must also
be examined.
The following research needs were
identified to evaluate the bioavailability
of TCDD relative to human health.
Matrices
The bioavailability of TCDD from ma-
trices of soil, fly ash, and respirable par-
ticles should be determined using the
same species and same toxicologic end
points. A range of concentrations
should be utilized, because the bioavail-
ability of TCDD may vary at differing
concentration levels.
Host Factors: Deposition and
Mobilization of TCDD
Because of the lack of knowledge of
the critical target organ(s) in humans,
studies are needed to determine the ap-
propriate animal species to use as mod-
els for studying host factors, tissue dis-
tribution, and mobilization from body
stores. Additionally, the critical end
points and other biochemical markers
need to be determined for both human
and other animal models.
One of the sensitive end points in an-
imals and possibly humans is the im-
mune system. The data that are avail-
able indicate further studies are needed
of the effects of TCDD on the immune
system.
The body burden of TCDD in humans
needs to be determined using adipose
tissue as the most important depot.
Studies determining the residue of
TCDD in other organs might indicate
possible target organs, as well as the
mobilization, redistribution, metabolic
pathways, and secretion or excretion
patterns in humans.
Pharmacokinetics and
Structure-Activity Relation-
ships
Because humans are often exposed
to mixtures of compounds that could in-
clude TCDD and similar chemicals,
studies are needed to delineate the in-
teractive effects of dioxin and furan iso-
mers with TCDD, and to determine the
additive, synergistic, or antagonistic ef-
fects, as well as the pharmacodynamics
of the mixtures and receptor level mod-
ulations.
Extrapolation of Animal Data
to Humans
An animal model that best indicates
TCDD toxicity in humans is being devel-
oped according to the criteria more fully
discussed in Chapter 3. Because there
are so many manifestations of TCDD
toxicity it may be necessary to have
more than one model, depending on the
end point.
Epidemiological Studies
Methods need to be developed to
identify persons who have been ex-
posed to TCDD and related compounds
as a basis for epidemiological studies.
Additional studies in humans should be
done with cohorts not exposed to TCDD
to establish the baseline for the end
points of toxicity. Rigorous epidemio-
logical studies with sound methods and
proper execution are needed to deter-
mine the effects of TCDD in humans.
Until there are better epidemiological
studies, the determination of TCDD tox-
icity will not be known with any assur-
ance, and the extrapolation of animal
data to humans cannot be done reliably.
Assay of TCDD
To perform many of the suggested
studies, there is a need to develop and
validate assays of TCDD that are accu-
rate, rapid, and economical, either in
vivo or in vitro, and that can be used to
determine the concentration of TCDD in
various organs.
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Gregory R. Grinder is the EPA Project Officer (see below).
The complete report, entitled "Report on the Research Planning Workshop on
Bioavailability of Dioxins—September 1984," (Order No. PB 86-175 676/AS;
Cost: $11.95. subject to change) will be available only from:
National Technical Information Service
5285 Port Royal Road
Springfield, VA 22161
Telephone: 703-487-4650
The EPA Project Officer can be contacted at:
Office of Environmental Processes and Effects Research
U.S. Environmental Protection Agency
Washington. DC 20460
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
Official Business
Penalty for Private Use $300
EPA/600/S9-86/004
0000327 PS
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