United States        Off ice of the Administrator    SAB-EC 86-011
Environmental Protection     Science Advisory Board     January 1986
Agency          Washington, DC 20460
Review of the
Status of Dioxin  Research
in the United States
Environmental Protection
Agency
Review of the
Dioxin Research Review
Subcommittee of the
Science Advisory Board

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             UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                           WASHINGTON. D.C.  20460

January 24,  1986


Honorable Lee M. Thomas
Administrator                                                        	    	
--  _  _  .        , _  .    . .   _                                TH.E—«"O"MINISTRATOR
U. S. Environmental Protection Agency                           ^
401 M Street, S. W.
Washington,  D. C.  20460

Dear Mr. Thomas:

     The Science Advisory  Board's  (SAB) Dioxin Research Review
Subcommittee has completed its review of the Agency's research program
for dioxins.  The Subcommittee carried out this review  at the request
of the Deputy Administrator and the Acting Assistant Administrator for
Research and Development.   It met  in public session in  Las Vegas,
Nevada on September 4-6, 1985 to discuss ongoing  and future research
with a number of Agency staff in the research and regulatory offices,
as well as staff from other Federal agencies.  The Subcommittee's
review was enhanced by the preparation of a document entitled "Status
of Dioxin Research in the  U. S. Environmental Protection Agency" that
described the program as of August, 1985.

     After reviewing the overall program, the Subcommittee concludes
that EPA has made substantial progress  in a number of areas in support
of the Dioxin Strategy.  As in any large research program starting up
in a crisis  atmosphere, there are  parts which, in hindsight, could have
been designed better and which could now perhaps  be redesigned or
dropped, and the funds redirected  to more promising research projects.

     The current research  program  is a mixture of short-term fire-
fighting and longer-range  efforts.  The need for  action at Superfund
sites, particularly in the case of dioxin contamination in Missouri,
has brought  rapid development and  deployment of a mobile incinerator.
Conversely,  the crisis context within which the total program has had
to exist has brought instability.  Funding for a  number of the projects
for FY 1986, for example,  was uncertain at the time of  the Subcommittee's
review.

     The Subcommittee concludes that the overall  management and direction
of the program should be strengthened.  We appreciate the difficulties
of managing and directing  a program that crosses  numerous administrative
boundaries and involves an array of scientific and engineering disciplines,
some of which may be outside the expertise of the Program Director.
Even so, a program of this magnitude and complexity requires a high,
well-defined level of authority vested  in the individual who has the
management responsibility.  It was not apparent that this was the case.

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                                 - 2 -
Also, it was not apparent that communications between project officers
and researchers were adequate.  For example, some of the project officers
presenting the research sponsored by the Agency were not thoroughly
familiar with the work conducted.  The Subcommittee believes that part
of this problem may be due to inadequate technical skills in the in-
house staff involved as project officers on these programs.

     The Subcommittee believes that not enough is known about the
environmental fate of the chlorinated dioxins and dibenzofurans.
Without a more complete understanding of this issue, scientifically
adequate risk assessments will be difficult to generate or justify.  We
believe this is particularly true for non-human biological populations
where exposure estimates are largely unknown.  This may be an area
where the Agency could expand its efforts, since it has the requisite
expertise.

     The Agency needs to more carefully define and articulate its research
role and capability with respect to other Federal agencies.  This is
particularly true with respect to the ongoing work at the National
Institutes of Health and the Centers for Disease Control.  Research carried
out and/or sponsored by these and other agencies may not always adequately
fulfill EPA's regulatory information requirements, but EPA should more
clearly state what its needs are.

     The Subcommittee reviewed the four major components of the dioxin
research program—technology assessment, monitoring, environmental
effects and health assessment.  Technical conments on the strengths and
weaknesses of these areas are included in the attached report.

     We appreciate the opportunity to work with the Agency in improving
the scientific base of knowledge related to dioxins and would welcome
any additional requests for SAB participation in the range of dioxin
issues facing the EPA.  We would appreciate a formal response to the
conclusions and recommendations included in this report.

                                   Sincerely,
                                   Robert Huggett, Chairman
                                   Dioxin Subcommittee
                                   Norton Nelson, Chairman
                                   Executive Committee

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                                      SAB-EO86-011
REVIEW OF THE STATUS OF DIOXIN RESEARCH
                 IN THE
 U. S. ENVIRONMENTAL PROTECTION AGENCY
  Dioxin Research Review Subcommittee
         Science Advisory. Board
 U. S. Environmental Protection Agency
             January 1986

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                                EPA NOTICE
This report has been wribten as a part of the activities of the Science
Advisory Board, a public advisory group providing extramural scientific
information and advice to the Administrator and other officials of the
Environmental Protection Agency.  The Board is structured to provide a
balanced expert assessment of scientific matters related to problems
facing the Agency.  This report has not been reviewed for approval by
the Agency, and hence the contents of this report do not necessarily
represent the views and policies of the Environmental Protection Agency,
nor does mention of trade names or commercial products constitute
endorsement or recommendation for use.

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                                                           August 1985
                  U. S. ENVIRONMENTAL PROTECTION AGENCY

                          SCIENCE ADVISORY BOARD

                   Dioxin Research Review Subcommittee
                                 Members
Chairman

Dr. Robert Huggett
College of William and Mary
Chairman, Department of
  Chemical Oceanography
Virginia Institute of
  Marine Science
Gloucester Point, VA  23062
Dr. Gil Addis
Electric Power Research
  Institute
P. 0. Box 10412
Palo Alto, California  94303
Dr. Martin Alexander (Co-Chairman)
Professor
Department of Agronomy
Cornell University
Ithaca, New York  14853
Dr. David Bayse
Centers for Disease Control
1600 Clifton Road
Atlanta, Georgia  30333

Dr. Bill Cooper
Virginia Institute of Marine Science
School of Marine Sciences
College of William and Mary
Gloucester Point, VA  23062
Science Advisory Board

Dr. Terry F. Yosie
Director
Science Advisory Board
U. S. Environmental
  Protection Agency
401 M Street, S. W.
Washington, D. C.  20460
Dr. H. Scott Fogler
3030 Dow Building
Department of Chemical
  Engineering
University of Michigan
Ann Arbor, MI  48109

Dr. William Lowrance
Senior Fellow and Director
Life Sciences and Public
  Policy Program
The Rockefeller University
1230 York Avenue
New York, New York  10021-6399

Dr. Wilbur McNulty
Oregon Regional Primate Center
505 NW 185th Avenue
Beaverton, Oregon  97006

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                            TABLE OF CONTENTS




                                                                  Page






Introduction 	      1



    A.  The Mandate for EPA's Dioxin Research Program 	      1



    B.  Subcommittee Review Procedures 	      3




    C.  Organization of the Subcommittee Report 	      4



Overview of Dioxin Research Program	-.	      4




Review of Technology Assessment 	      5



Comments on Individual Technology Assessment Projects	      6



    Project I.    In-Situ Stabilization 	      6



    Project II B. White Rot Fungus	      6



    Project III.  Shallow Mines as Repositories 	      7



    Project IV.   Mobile Incineration 	 	  .    7



    Project V.    Chemical Detoxification Using APEG 	      7



Review of Monitoring Research 	      7



Comments on Individual Monitoring Research Projects 	      9



    Project I.    Methods Development for 2,3,7,8—TCDD 	      9



    Project II.   Methods Development—Round Robin Survey ....      9



    Project III.  Quality Assurance 	     10



    Project IV.   GC/MS Methods Development  	     10



Review of Environmental Effects Research 	     10



Comments on Individual Environmental Effects Research Projects     11



    Projects I. II. Fate of Dioxins and Sorption/Desorption...     11



    Project III.  Uptake of Dioxins by Fish	     11



    Project TV.   Uptake of Dioxins by Plants 	     11

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                                  - 2 -
    Projects V and VI. Uptake and Bioavailability of Dioxins
                  by Animals 	     12

Review of Health Assessment Research 	     12

Garments on Individual Health Assessment Research Projects ...     13

    Project I.   Risk Assessment 	     13

    Project II.  Exposure Assessment 	     13

    Project III. Pharmacokinetics in Rhesus Monkeys 	     13

    Project IV.  NIOSH Dioxin Registry 	     13

    Project V.   Monoclonal Antibody Assay 	     13

    Project VI.  Short-Term Bioassays for TCDD1s 	     14

    Structure-Activity Relationship (SAR) Studies 	     14

    Marmoset Toxicology .........-.-.-	     14

Appendix A:

    Agenda for the September 4-6, 1985 Meeting

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Introduction
     At the request of the Deputy Administrator of the Environmental
Protection Agency and the Acting Assistant Administrator for Research and
Development (ORD), the Science Advisory Board (SAB) agreed to conduct
scientific reviews of a number of ORD programs.  The purpose of these
reviews is to enable recognized, independent scientists and engineers to
review ongoing research programs in order to: 1) communicate to the
Agency the progress, or lack of progress, made in identifying the research
needs and acquiring high quality technical data needed for risk assessment;
2) assess whether EPA has clearly stated the objectives of the program
and ensured that individual projects are consistent with these objectives;
3) recommend steps to improve the structure and future direction of the.
research program.  In August, 1985, the staff of the Office of Research and
Development prepared a document entitled "Status of Dioxin Research in
the U. S. Environmental Protection Agency"/ which they asked the SAB to
review.  The Board formed a Dioxin Research Review Subcommittee to evaluate
these issues as they relate to dioxin research planned, sponsored or
carried out by the Agency.

     A.  The Mandate for EPA's Dioxin Research Program

     Shortly after its formation in December, 1970, EPA began its dioxin
research efforts after 2,3,7,8-tetrachlorodibenzo^p-dioxi-n was. identified
as a contaminant of'the widely used herbicide 2,4,5-trichlorophenoxy
acetic acid.  At that time, the research focused on developing a methodology
to detect 2,3,7,8-TCDD in environmental samples.  With increasing public,
scientific and Congressional interest and concern over dioxin contamination,
EPA has expanded its research program to include human health and environ-
mental effects, disposal methods and monitoring.  The Congress has increased
research to the level of $2.4 million in Fiscal Year (FY) 1984 and $3.0
million in FY 1985.  Additional monies were allocated through the Superfund
program for a demonstration of the mobile incinerator.  In FY 1986, EPA
plans to expend approximately $3.7 million in dioxin related research.
In addition, the Congress has directed EPA to study dioxins and other
chlorophenols by monitoring specific dioxin contaminated areas and by
performing a national screening study (the "National Dioxin Study") to
identify the relative concentrations of dioxin in other areas of the
United States.

     In parallel with the increased Congressional and public concern over
dioxin exposures, EPA formulated a National Dioxin Strategy, published
in November, 1983.  The Strategy represents an attempt to respond to the
Congressional requirements and to integrate the numerous current research
and regulatory efforts related to dioxins by assigning responsibilities
to various EPA offices.  The Strategy is subdivided into seven tiers,
identified below by EPA staff in descending order of importance:

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                                  - 2 -
     Tier 1 	 Current and former sites of 2,4,5-trichlorophenol
                 production.

     Tier 2 	 Current and former sites where 2,4,5-TCP was used
                 as a precursor to develop another chemical product.

     Tier 3 	 Current and former sites where 2,4,5-TCP and its
                 derivatives were used to develop pesticides.

     Tier 4 	 Assessment of combustion sources of dioxins.

     Tier 5 	 Sites where 2,3,7,8-TCDD contaminated pesticides have
                 been or are being used.

     Tier 6 	 Production of other chemical products lending to
                 the formation of 2,3,7,8-TCDD.

     Tier 7 	 Control sites to evaluate background dioxin levels.

     EPA has also participated in interagency exchanges of dioxin
information through the Federal Agent Orange Work Group and in international
forums, such as- the North Atlantic Treaty Organization's Committee on
Challenges to Modern Society.

     EPA has completed-,-or-has in progress; various remedial or regulatory
actions that it implements through various authorizing statutes'.  Examples
of these activities include:

     o  Clean Air Act evaluation of dioxin as a hazardous air pollutant.

     o  Banning of dioxin under Resource Conservation and Recovery Act
        waste stream listings, development of standards and guidance for
        land disposal and other treatment, storage and disposal technigues
        and design and operating guidelines for municipal waste incinerators.

     o  Data acquisition and reporting requirements under the Toxic
        Substances Control Act to identify manufactured products that
        may lead to exposure to polychlorinated dibenzo-p-dioxins and/or
        polychlor i nated d ibe nzofurans.

     o  Remedial actions at hazardous waste sites authorized by the
        Comprehensive Environmental Response Compensation Liability Act
        (Superfund).

     o  Clean Water Act Section 307 (a)(2) listings of hazardous pollutants
        in surface waters.

     o  Pentachlorophenol Rebuttable Presumption Against Registration
        (RPAR) actions conducted under the auspices of the Federal
        Insecticide, Fungicide and Rodenticide Act (FIFRA).

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                                  - 3 -
     o  Proposed Maximum Contaminant Levels for dioxins in drinking water
        set under decision criteria established by the Safe Drinking
        Water Act.

     EPA's dioxin research program is designed to satisfy the technical
data needs generated by these classes of activity.  At present, the
program has four major components:

     o  Technology assessment—evaluating technologies for their
        capabilities to control, detoxify or ultimately destroy dioxins.

     o  Monitoring-rdeveloping analytical techniques and quality assurance
        procedures to identify and quantify dioxins within biotic and
        aquatic matrices.

     o  Environmental effects—considering the fate, mobility and effects
        of dioxins in the environment and their uptake and bioavaliability
        in plants and living systems.

     o  Health assessment—developing data and methodologies to evaluate
        human health exposure and risks associated with dioxins to provide
        the necessary- documentation for exposure and-r-isk assessments. 	

     The Subcommittee received budget data for Fiscal Years 1984, 1985,
and 1986 for each of these program areas.

     B.  Subcommittee Review Procedures

     The Subcommittee met in public session in Las Vegas, Nevada on
September 4-6, 1985 to review the dioxin research program.  The Office of
Research and Development prepared for the Subcommittee a briefing document
entitled "Status of Dioxin Research in the U. S. Environmental Protection
Agency" that described the program and its components as of August, 1985.
The Subcommittee compliments the Agency staff for this useful documentation.
Its review could not have proceeded as thoroughly and expeditiously in
the absence of such a document.  The Subcommittee recommends that the
Agency distribute this document in revised form to the public and the
Congress to further inform them of the ongoing dioxin research program.

     The review meeting proceeded in three phases.  EPA officials from
various offices discussed the evolution of the dioxin-related activities
since the formation of the Agency, the formulation of the National
Dioxin Strategy and ongoing regulatory actions and information needs, the
activities of various EPA regional offices, the development of the National
Dioxin Survey and interagency and international coordination efforts.
Second, the Subcommittee listened to in-depth briefings and provided
technical comments on the four research program areas.  The specific

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                                  - 4 -
research topics discussed within these areas are identified in the meeting
agenda which is enclosed as Appendix A.  Third, the panel held a planning
and writing session to draft its key conclusions and recommendations.

     C.  Organization of the Subcommittee Report

     The Subcommittee presents its technical evaluation of the dioxin
research program at three distinct levels.  These include:

     o  A review of the research program relative to the information needs
        articulated by the Dioxin Strategy and the regulatory offices, and
        identifying other technical needs not addressed by these means.

     o  An assessment of the quality and direction of individual research
        program components: technology assessment, monitoring, environmental
        effects and human health assessment.

     o  A critique of the merits of individual research projects encompassed
        in the dioxin research program.

At each of these levels, the Subcommittee presents its key conclusions and
recommends changes in EPA's current and planned research efforts.

Overview of the Dioxin Research Program

     After reviewing the overall program, the Subcommittee concludes that
EPA has made substantial progress in a number of areas in support of the
Dioxin Strategy.  As in any large program starting up in a crisis
atmosphere, there are parts which, in hindsight, could have been designed
better and which could now perhaps be redesigned or dropped, and the
funds redirected to more promising research' projects.

     The current research program is a mixture of short-term fire-fighting
and longer-range efforts.  The need for action at Superfund sites, partic-
ularly in the case of dioxin contamination  in Missouri, has brought rapid
development and deployment of a mobile incinerator.  Conversely, the
crisis context within which the total program has had to exist has brought.
instability.  Funding for a number of the projects for FY 1986, for
example, was uncertain at the time of the Subcommittee's review.  This
has in part led to some unimaginative planning, examples of which are
noted in this report.

     The Subcommittee concludes that the overall management and direction
of the program should be strengthened.  We  appreciate the difficulties of
managing and directing a program that crosses numerous administrative
boundaries and involves an array of scientific and engineering disciplines,
some of which may be outside the expertise  of the Program Director.  Even
so, a program of this magnitude and complexity requires a high, well-
defined level of authority vested in the individual who has the management
responsibility.  It was not apparent that this was the case.  Also, it
was not apparent that communications between project officers and

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                                  - 5 -
researchers were adequate.  For example, some of the project officers
presenting the research sponsored by the Agency were not thoroughly
familiar with the work conducted.  The Subcommittee believes that part of
this problem may be due to inadequate technical skills in the in-house
staff involved as project officers on these programs.

     EPA needs to carefully evaluate the limits of its ability relative to
other Federal institutions to conduct human health research.  Agencies
such as the National Institutes of Health (NIH) and the Centers for Disease
Control (CDC) are mandated to carry out these efforts.  They are also
more experienced in these types of endeavors.  The Subcommittee does not
imply that the Agency should not maintain a competent staff with an
expertise in the human health effects of pollutants.  It is essential
that such a capability exist in order for EPA to fully evaluate the
effects of environmental contaminants.  The Subcommittee also recognizes
that research carried out by other Federal agencies may not be adequate
to fulfill EPA's regulatory information requirements.  We recommend that
EPA more explicitly state its role as a research agency in relation to
these other dioxin related efforts and, in particular, articulate health
research needs that are not likely to be addressed by NIH or CDC.

     The Subcommittee believes that not enough is known about the environ-
mental fate of the chlorinated dioxins and dibenzofurans.  Without a more
complete understanding of this issue, scientifically adequate risk assess-.
ments will be difficult to generate or justify.  We believe this is
particularly true for non-human biological populations where exposure
estimates are largely unknown.  This may be an area where the Agency
could expand its efforts, since it has the requisite expertise.

     We believe that the Agency's effort to become more involved in the
international efforts to study and/or regulate dioxins is commendable,
particularly in view of the considerable amount of research being conducted
in other countries.

     The creation of a dioxins research registry would also be useful for
communication and coordination.  This registry would contain information
on all past and present dioxin projects in this country as well as
abroad.  It would provide immediate access to needed information by
managers, scientists and engineers.  The benefits of such a registry
could range from better scientific designs for research to avoidance of
duplication of effort.

Review of Technology Assessment

     The options for the control, detoxification or destruction of dioxins
are limited.  They include storage, preferably by immobilization;
chemical detoxification; thermal destruction; and separation from the bulk
matrix.

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                                  - 6 -
     The Agency has partially evaluated these options relative to existing
technologies.  Research is ongoing, but evaluations are not complete.
The Subcanmittee offers several comments concerning the appropriateness
of available technologies:

     o   Storage is only temporary, and a disproportionate use of this option
         will merely delay the disposal problem until some future time.

     o   If proper disposal techniques can be developed, chemical treatment
         may be the most effective' method for detoxifying material containing
         low dioxin concentrations.

     o   Thermal destruction may be quite efficient for the elimination of
         dioxins in the presence of high concentrations of organic materials
         such as still bottoms and grossly contaminated soils.

     o   Removing dioxins from the soil matrix, followed by their concentration,
         and thermal destruction may offer a useful compromise.

     Future research efforts in this portion of the program should be
designed with these points in mind.

Comments on Individual Technology'Assessment: Projects."''.:'.'

Project I.  In-Situ Stabilization

     In-situ soil stabilization appeared to present only a temporary
measure at best.  Possibly it could be used as a holding action awaiting
development of a better technology.  Concrete, even if it was otherwise
suitable, could present a problem if the soil is to be removed later for
further treatment.  Asphalt would itself be biodegradable in a moderate
period of time and, hence, the dioxins would again be available.
Plastics, such as epoxy, are susceptible to atmospheric weathering.  A
more stable product might result fron vitrification.  However, the merits
and demerits of this technique to encapsulate organic components are
currently unknown.

     This project does not merit further funding.

Project II. B.  White Rot Fungus

     The Subcommittee emphasizes that the dioxin destroying ability of
white rot fungus has been demonstrated only in solution under controlled
laboratory conditions and, even here, a more rigorous demonstration is
needed to confirm that the dioxin and not a chemcial contaminant is being
degraded.  It is essential to determine whether the fungus can function
in natural environments where physical obstructions to microbial movement
may exist.  Secondly, dioxin may not be readily available or it may be
too strongly bound to the soil to be easily removed by the fungus.

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Finally, the presence of competing microorganisms, predators, and parasites
in the natural environment may prove to be detrimental to the effectiveness
of this method.  The Subcommittee suggests that field research, which is
subject to many uncontrolled variables, not be conducted until studies
with laboratory soil microcosms are completed and show positive results.
Furthermore, such tests should be reviewed by personnel fully familiar
with biological studies in soils or soil microcosms.

Project III. Shallow Mines as Repositories

     If a cost-effective destruction process does not become readily
available, storage in mines may be the most expedient short-term compromise.
The means of packaging should be examined more carefully in relation to
the planned storage life.  Corrosion of metal drums and aging of plastic
sacks should be taken into consideration.  The drawback ot this technique
is that storage simply passes the problem on to future generations.

Project IV. Mobile Incineration

     The Subcommittee believes that the Agency performed an excellent
engineering job, under severe pressures for rapid completion, during the
test burns of dioxin contaminated soil in Missouri.  Results should be at
least as good as-the*.best" of the commercial incinerators.  The Subcommittee,
believes, however, that for future use of the incinerator, the Agency
should also analyze whether it is emitting toxicants not currently measured
in the analyses of stack gases.  Seme Subcommittee members were concerned
as to whether it was prudent to permit an operating range of up to 100
parts per million carbon monoxide before sounding the alarm.  The Subcommittee
suggests that modeling of the control system of the incineration process
is desirable.

Project V. Chemical Detoxification Using Alkaline Polyethylene Glycol (APEG)

     The data generated to date by experiments designed to determine the
potential of APEG as a detoxifying agent lead the Subcommittee to believe
that a field evaluation experiment is not warranted because it is not yet
apparent that the substance has a likelihood of being effective.  We
reconmend that laboratory experiments be designed and conducted to
demonstrate its effectiveness under controlled conditions.  These include
soils of different types and different organic and moisture contents.
The results should then be evaluated to determine its potential usefulness
in the environment.

Review of Monitoring Research

     The Agency stated two major goals for this component of the research
program: 1) to produce standardized analytical procedures to detect and
measure chlorinated dibenzo-p-dioxins  in environmental samples, and 2) to
establish quality assurance practices to support their routine use.

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                                  - 8 -
     To achieve these goals, EPA has emphasized the development of well
characterized standards of 22 tetra congeners of chlorinated dioxins and
plans, in the future, to repeat the approach for the chlorinated dibenzo-
furan congeners.  The Subcommittee supports the basic approach presented
by EPA, but we suggest a broader and more comprehensive program with more
explicitly stated objectives.  The following discussion, in part, indicates
the areas that need expansion.

     The Agency should develop a more detailed list of halogenated organics
of present and possible future concern for the National Dioxin Strategy.
This list should be cross-indexed with known and needed information on
toxicity, and transport and fate.  In all cases, these needs should be
coordinated with other areas of the dioxin program.  This listing, at a
minimum, should contain all of the congeners of halogenated dibenzo-dioxins
and dibenzo-furans.  The Agency interest in the products of combustion,
both from an industrial pollution as well as from a clean-up perspective,
should lead to an immediate expansion of the listing beyond the organic
compounds presently mentioned.  Based on the preceding, the Agency should
prepare a detailed three to five-year plan for synthesizing the necessary
organic compounds in appropri-ate quantities.

     The Agency significantly underestimates the present and future need  "
for standard reference materials, in a wide, variety of matrices.  These    . .
materials should be produced and documented not only to the specification
associated, with primary standards but also to mimic environmental matrices.
An increased research effort, followed by a production effort, will be
necessary to meet this need.

     All meaningful environmental data, no matter how elegantly quantitated,
are no better than the sampling protocol used.  Improved sampling protocols
need to be developed, particularly in conjunction with research projects.
These improvements can be assisted by at least four approaches:

     o   Incorporating well-planned sampling designs as part of the
         initial research plans.  Even with the availability of excellent
         analytical methods, the data have little value unless they are
         derived from a program with an adequate and validated sampling
         design.

     o   Recognizing sampling techniques as an important research
         focus.

     o   Adding statisticians as part of the research team.

     o   Using analytical methods with rapid screening capability
         to significantly increase the number of samples that could be
         processed.

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                                  - 9 -
This last point would not only have an effect on research but also
on the service component.  State public health laboratories have
indicated that the development of screening methods in the environmental
area is one of their greatest needs.

     The development of a highly flexible and responsive analytical
chemistry capability (standards, methods, and QC procedures) that is
highly coordinated with a reserve service capacity is needed within the
Dioxin Strategy in order to cope with emergencies.  This capability
should be based within EPA.  Dioxin-contaminated sites are but one example
where chemical emergencies have called for using unique analyses..  These
development and service demands were not off-the-shelf items.  Many
times, the issues at stake are of such importance that EPA should not
rely only on contract laboratories to document the level of environmental
contamination.  The Agency should have the capability to conduct very
highly sophisticated qualitative and quantitative analyses as part of its
research program.  Highly trained chemists in a wide variety of disciplines
supported by the very latest equipment are necessary to solve these
difficult analytical problems.

Comments on Individual Monitoring Research Projects

Project 1.  Methods Development for 2,3,7,8—TCDD

     The development of a standardized method for measuring of 2,3,7,8-
TCDD is of fundamental importance to the dioxin program.  The EMSL (Las
Vegas) staff clearly demonstrated the analytical expertise necessary to
carry out this task by their significant progress in this project.  The
cooperation that is considered essential by the Subcommittee was shown to
be present by the creation and functioning of the TROIKA.  Although the
laboratories were equipped for this project, there is a need to further
modernize the equipment used.

Project II.  Methods Development—Round Robin Survey

     The coordinated use of resources among agencies involved in environ-
mental programs is essential.  This project demonstrates the Agency's
ability to coordinate the use of in-house and external resources.  One of
the important objectives that is targeted for increased support in the
preceding overview is the need for standard reference materials in a
variety of matrices.  The strength of this project was the material
preparation and the determination of the dioxin concentration.  However,
increased attention to the complete and formal documentation of such
material in the future will demand greater involvement of the research
laboratory in the initial phases of such a project.  Laboratory resources
for this purpose must be maintained and highly coordinated inside EPA.

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                                  - 10 -
Project III.  Quality Assurance

     The numerous congeners of dioxin increase the complexity of the
analysis, making the availability of high quality standards essential
to assure specificity.  Cooperative programs between EPA and CDC to
produce standards for the dioxins and furans is mutally beneficial
and will increase cooperation in other areas of both agencies' environ-
mental programs.  The unresolved problem of the qualitative and quantitative
characterization of the incineration emissions should become a high
priority of the quality assurance effort.

Project IV.  GC/MS Methods Development

     A more forward looking plan as part of the Dioxin Strategy is needed,
and this project begins to address this issue.  More staff and increased
resources need to be directed beyond just the chlorinated dioxins and
furans to other closely related halogenated products of combustion.

Review of Environmental Effects Research

     The development of exposure assessments requires an evaluation of
the .importance, first qualitatively and then quantitatively, of all
likely pathways of contamination.  Chemicals bound to soil particles are
transported laterally with eroding soil and, thus, they contaminate aquatic
sediments where many fish commonly feed.  Many chemicals that persist in
soil enter the air in significant amounts because of their volatility,
and many are subject to aerial dissemination when emitted from municipal
and industrial combustion processes.  The significance of these modes of
transport for dioxin should be established to provide a meaningful basis
for evaluating and managing risks.

     Since the purpose of this research is to provide an estimation
of the'critical elements in the exposure assessment models, any future
efforts should specifically relate to the priority needs of the model.

     EPA assigns low priority to the issue of dioxin transformations in
nature.  The chemical, for example, may be destroyed by photochemical
reactions and, thus, aerial dissemination may not pose a hazard.  Other
means of transformation in air, water, sediments, and soils seem less
likely in view of the apparent persistence of dioxin, but major information
gaps may still exist.  For example, there exists a slow microbial degradation
of the chemical, but the rates of such degradation, the products of the
reaction, and the human toxicity of these metabolites are unknown.
Studies of these transformations are needed.

     A study on transport and fate of dioxin should include at least the
following scientific disciplines: chemistry, engineering, soil science,
ecology and microbiology.  At least one specialist in each of the disciplines
must be intimately involved with the study in order to assure that the
proper experimental design and subsequent interpretation of results occur.

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                                  - 11 -



Comments on Individual Environmental Effects Research Projects

Projects I and II.  Fate of Dioxins and Sorption/Desorption

     The results of two soil studies conducted thus far leave a number
of unanswered questions.  Except in special circumstances, vertical
movement through soil to contaminate ground water does not appear to be a
significant route for human exposure.  However, movement in soil channels
has yet to be evaluated, and its significance should be assessed.  Research
is required on other aspects of soil-dioxin transport.

     Adequate information now exists that dioxin is strongly sorbed by
soil constituents, and it is difficult to justify much additional research
in this area in comparison to other major data needs.  A major exception
is the possible transport of dioxin through soil in the presence of
organic chemicals in waste disposal sites.  With the acknowledged slow
mobility of dioxin through soil, shortterm studies with distilled water
as the solvent (such as those that have been recently completed) can no
longer be scientifically justified since the issue is mobility over long
periods with constituents of soil solution or with organic solvents at
those sites containing, such chanicals.  Even in these instances, the
organic solvents must have prolonged persistence because their, elimination  ..
by volatilization or biodegradation would result in an essentially immobile
dioxin front.

Project III.  Uptake of Dioxins by Fish

     Since a majority of the human exposure to dioxins is probably occurring
through the unregulated activity of sportfishing, gathering data on the
uptake and bioaccumulation by fish is critical.  EPA should consider
laboratory experiments utilizing benthic invertebrates that are detritivores,
and organically bound dioxins.  In general, the EPA scientists assessing
dioxin uptake by fish are competent, and this research activity is off to
a good start.

Project IV.  Uptake of Dioxins by Plants

     The Subcommittee fails to see the significance of growing soybeans
in solution culture for assessing the risk of dioxins.  First, dioxins are
almost entirely bound to soil.  Second, the chemicals generally are all near
the soil surface.  Third, soybeans do not represent the type of plant
present in areas where there may be significant soil contamination.

     Nevertheless, more work is needed on the uptake of dioxins from
contaminated soils, as well as translocation of the chemicals to edible
portions of plants fron root systems or from the aerial portions of plants
likely to be exposed to dioxins from atmospheric fallout.  Edible portions
in this context refers to parts of the plant directly consumed by humans
or entering the human food supply through livestock or other animals.

     Some areas of future research on dioxin uptake by plants which may
be useful include:

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                                  - 12 -
     o   The potential relationship among the length of time of exposure
         of soil to TCDD, the introduction of plants to contaminated soil
         and the availability of TCDD for plant uptake.

     o   The chemistry of TCDD in the soil solution in relation to uptake
         by terrestrial plants.

     o   The possibility of different responses to TCDD by different
         species or categories of plants.

     o   The physiological mechanisms of TCDD uptake and its translocation,
         fate, toxicity (if any), and/or metabolism (if any) in each
         plant species evaluated.

     o   The effect of phenology on physiological processes involving TCDD
         activity in each plant species evaluated.

     Research designed to add to our understanding of these areas would
greatly increase our knowledge about the activity of TCDD and related
compounds in both plants and the environment.

Projects V and VI.  Uptake and Bioavaliability of Dioxins by Animals

     The study of the partitioning of dioxins to various tissues and
organs within a dairy cow is strictly descriptive but still useful.
The effects of anaerobic metabolism in the cow's rummen on the metabolism
of dioxin should be considered in more detail.  The partioning of daughter
products must be considered if metabolism does occur.

     The guinea pig study needs a careful evaluation relative to its
likelihood of generating data useful to the Agency.  Black box experiments
utilizing Times Beach and Newark soils leave a lot to be desired.  A
series of good experiments with controls or quantitative gradients of
soil parameters and specific sets of mechanistic hypotheses should be
developed.

Review of Health Assessment Research

     The Subcommittee experienced difficulties in reviewing the Agency's
health assessment work, in part because it was not clear how EPA's
health research and/or assessment mission should be distinguished from that
of other Federal agencies, particularly the Centers for Disease Control.
Since EPA's information needs will not be met exclusively through studies
conducted by other agencies, the Subcommittee understands the need for an
EPA research program.  Maintaining such a program will also enhance the
Agency's capability to maintain inhouse expertise.  The Subcommittee was
not impressed with the Agency's efforts to date to define its health research
mission for dioxins or to sustain a program that incorporates a critical
mass of health effects studies over the long-term.

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                                  - 13 -

Comments on Individual Health Assessment Research Projects

Project I.  Risk Assessment

     A major effort should be made to reduce the various uncertainties in
the risk assessments.  Agency scientists clearly recognize the imprecision
in these assessments, as indicated in part by a recently prepared EPA
comparison of the assessment approaches used by EPA, CDC, and the Food
and Drug Administration (the Subcommittee did not receive this document
until after the Las Vegas meeting, so we did not have a full opportunity to
discuss it).  These assessments represent both the outcome of the ongoing
research program and the feedback for planning future research and
development.  In the coming months, it will be important to dovetail the
EPA laboratories' plans with the conclusions-of the Health Assessment
Document for Dioxins now being finalized -by the Office of Health and
Environmental Assessment.  This is as much a research management problem
as a technical one.  The intentions listed in the background document
prepared for this review are reasonable.  These include updating and
broadening the consideration of exposure and bioavailability, and studying
such noncarcinogenic health effects as developmental toxicity and
immunotoxic ity.

Project II.  Exposure Assessment.

     Most of the exposure-estimation research presented to the Subcommittee
has been addressed in other'sections of- this report.  The average steady-
state body burden of the general population needs to. be analyzed and its
implications considered for the regulation of both ambient and episodic
environmental exposure to dioxins.

Project III.  Pharmacokinetics in Rhesus Monkeys

     This study at the University of Wisconsin, despite having gotten off
to a weak start and involving only eight animals, is' one of the few
primate studies of TCDD being conducted anywhere.  It holds valuable
promise, and EPA should pursue it thoroughly.  The pharmacokinetics deserve
to be measured on more of the animals than those analyzed to date, especially
to confirm the distribution, depuration rate, and intake/burden ratio;
this information will be relevant to estimating these values in humans.  The
general and reproductive toxicology and pathology also need to be pursued.

Project IV.  NIOSH Dioxin Registry

     This is not fully an EPA research project, even though the Agency is
partially funding it. The creation of a dioxins research registry would
contain information on all past and present dioxin projects in this>
country as well as abroad.  It would provide immediate access to needed
information by managers, scientists and engineers.  The benefits of such
a registry could range from better scientific designs for research to
avoidance of duplication of effort.

Project V.  Monoclonal Antibody Assay

     The Subcommittee was not impressed with the objectives or promise of
this rather nonspecific assay work (conducted primarily by Oak Ridge
National Laboratories).  The preliminary results presented to us did not
indicate that the assays are likely to detect dioxins or furans with

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                                  - 14 -
specificity in environmental samples, nor that they are likely to be able
to detect these materials in the required parts-per-trillion range.

Project VI.  Short Term Bioassays for TCDDs

     Several approaches for screening environmental samples for dioxins
were mentioned, but none was discussed in detail (except for the monoclonal
antibody technique, above).  Vfe are not able to evaluate these lines of
research.  It is clear that rapid screening techniques are desirable.

Structure-Activity Relationship (SAR) Studies

     Although the Subcommittee-believes this approach is promising, the
rather elaborate SAR project described did not seem to be important for
solving the medium-term environmental dioxin problem.  The Agency does
need to develop experience with these methods, but because of the many
dioxin congeners and the lack of correlated biological information it is
not clear that the dioxin congeners make a good test case.

Marmoset Toxicology

     The proposed marmoset reasearch (in Germany) described to the
Subcommittee -seems interesting> in part because the animals are more
tractable than many other primates.  But because the reproductive system
of female marmosets is very different from that of humans, the relevance
for human protection is not direct.  The Subcommittee was not convinced
that this study is a high-priority research undertaking.

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                                                  APPENDIX A
                        AGENDA








                SCIENCE ADVISORY BOARD






           REVIEW OF DIOXIN RESEARCH IN EPA








                 September 4-6, 1985








At the Environmental Monitoring and Systems Laboratory






                  Las Vegas, Nevada

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September 4, 1985
 8:00 a. m.

 8:15 a. m.


 8:30 a. m.


 9:15 a. m.

10:00 a. m.

10:15 a. m.


10:45 a. m.


11:00 a. m.



12:00 noon

 1:00 p. m.
                Introductory Remarks and Objectives

                SAB Perspective


                The Dioxin Problem:
3:30 p. m.

5:30 p. m.
                An Interagency Perspective

                Dioxin Strategy and EPA Program Needs

                Coffee Break

                Dioxin Activities;
                A Regional Perspective

                Dioxin Research in EPA;
                Overview

                National Dioxin Survey

                Discussion

                Lunch

                Review of Technology Assessment
                Research

                Introduction

                o  In situ Stabilization of
                   Contaminated Soils
                o  Shallow Mines as Repositories
                o  Mobile Incineration
                o  UV/APEG Detoxification
                o  White Rot Fungus
                o  PCB Transformer/Capacitor Wires

                Discussion

                Social Hour
                                                         Erich Bretthauer

                                                         Terry Yosie
                                                         Robert Huggett

                                                         Donald Barnes
                                                         John Milliken
                                                         Morris Kay
                                                         Ralph Hazel

                                                         Rizwanul Hague
                                                         Norbert Jaworski
                                                         Paul desRosiers

                                                         Don Sanning

                                                         Don Sanning
                                                         Frank Freestone
                                                         Charles Rogers
                                                         Al Klee
                                                         Al Klee

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September 5, 1985
10:45 a. m.

11:15 a. m.
 7:30 a. m.       Executive Session
                  Breakfast Meeting

 8:00 a. m.       Tour of the EMSL-Las Vegas Facility

 9:00 a. m.       Review of Monitoring Research

                  Introduction

                  o  Methods Development
                     for Dioxins
                  o  Round Robin Survey for
                     Adipose Tissue Analysis
                  o  Quality Assurance and
                     Reference Standards

                  Discussion

                  Review of Environmental Effects
                  Research

                  Introduction

                  o Sorption Characteristics
                    of TCDD in Soils
                  o Mobility of 2,3,7,8-TCDD
                  o Bioavailability to Fish
                  o Bioavailability to
                    Laboratory Animals
                  o Uptake by Plants
                    and Large Animals

12:30 p. m.       Lunch

 1:30 p. m.       Discussion

 2:30 p. m.       Review of Health Assessment Research

                  Introduction

                  o Risk Assessment for 2,3,7,8-TCDD
                  o Exposure Assessment Methods
                  o Pharmacokinetics in Rhesus
                    Monkeys
                  o Antibody Research
                  o Health Effects Research

 4:30 p. m.       Discussion

 5:30 p. m.       Concluding Remarks
                                                         Michael Dellarco

                                                         Ron Mitchum/
                                                           William Budde
                                                         Robert Harless

                                                         Ron Mitchum
                                                         Rizwanul Hague

                                                         Mike Roulier

                                                         Marvin Piwoni
                                                         Philip Cook
                                                         Rizwanul Hague

                                                         Craig McFarlane
                                                         Charles Nauman

                                                         Charles Nauman
                                                         Charles Nauman
                                                         Peter Voytek

                                                         Michael Dellarco
                                                         Richard Phillips
                                                         Erich Bretthauer
                                                         Terry Yosie
                                                         Robert Huggett

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September 6, 1985
 9:00 a. m. - 4:30 p. m.    Subcommittee Report Preparation—
                            Executive Session

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