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Unfed StatM $d*m» Advfcory EPA-SAB-EPEC-32-OZ4
Environment*! Bo*n( (A-1011 August 1992
AN SAB REPORT: REVIEW
OF RATIONALE FOR
DEVELOPMENT OF AMBIENT
AQUATIC LIFE WATER
QUALITY CRITERIA FOR
TCDD (DIOXIN)
PREPARED BY THE DIOXIN ECOTOX
SUBCOMMITTEE OF THE
ECOLOGICAL PROCESSES AND
EFFECTS COMMITTEE
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON D.C. 2
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Medaka, is inherently controversial and EPA should consider substitute species that are native
or modify the guidelines for developing water quality criteria. The Subcommittee also
recommends that EPA add tests to evaluate metabolism of dioxin, biomarfcers such as
immuriosuppression and preneoplastic lesions, and improve analytical measurements and
verify aqueous concentrations. Such information would support the development and
implementation of the criterion. The Subcommittee finds that the TEF approach is
promising, but further verification must be done before it can be applied to aquatic life and
wildlife. Overall, EPA has presented several alternatives to conventional testing of chemicals
which, if verified by additional research, will provide valuable insights about compounds that
bioaccumulate. This research may also lead to a new approaches for criteria that should be
reflected in the national guidelines for developing water quality criteria. These and other
recommendations are elaborated in the attached report.
Finally, the SAB would like to express concern about the limited resources for the
ongoing dioxin environmental research effort. We hope that the situation is corrected as soon
as possible so this valuable research can continue.
The Science Advisory Board appreciates the opportunity to conduct this important
review and we look forward to reviewing the Agency's progress in revising the National
Guidelines for Water Quality Criteria and developing an accumulation-based hazard
evaluation. For this research plan, we are particularly interested in whether the Agency will
be able to include additional test organisms and verify critical assumptions as part of the
overall research plan.
Sincerely yours,
C.
ymond Loehr, C
Executive Committee
Science Advisory Board
eth. Dickson, Chair
Ecological Processes and
Effects Committee
Robert Huggdft
Dioxin Ecotox Subcommittee
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U.S. ENVIRONMENTAL PROTECTION AGENCY
NOTICE
This report has been written as a part of the activities of the Science Advisory Board,
a public advisory group providing extramural scientific information and advice to tlie
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 or other agencies in Federal government. Mention of trade
names or commercial products does not constitute a recommendation for use.
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US ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOABD
Dioxnsr ECQTQX SUBCOMMTITEE
CHAIRMAN
DR. ROBERT J, HUOOETT, Professor, VA Institute of Marine Sciences, College of
William and Mary, Gloucester Point, Viginia
MEMBERS/CONSULTANTS
DR. WILLIAM I. ADAMS, ABC Laboratories, Columbia, Missouri
DR, PHILIP B. DQRN, Shell Development Company, Houston, Texas
DR. JOHN C. HARSHBERGER, National Museum of Natural History,
Smithsonian Institute, Washington, D,C.
DR. ROLF HARTUNG, Professor, School of Public Health, University of Michigan,
Ann Arbor, Michigan
DR. RICHARD F. LEE, Sltidaway Institute of Oceanography, Savannah, Georgia
DR. ANTHONY F. MACIOROWSKI, National Fisheries Research Center, US FWS,
Kearneysville, West Virginia
DR. KAREN McBEE, Assistant Professor, Department of Zoology, Oklahoma State
University, StiUwater, Oklahoma
SCIENCE ADVISORY BOARD STAFF
DR. EDWARD S. BENDER, Designated Federal Official, US EPA/Science Advisory
Board, 401 M Street, S.W., (A-101F), Washington, D.C. 20460
MRS. MARCIA K. JOLLY (MARCY), Secretary to the Designated Federal Official
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ABSTRACT
The report represents the conclusions and recommendations of the U.S. Environmental
Protection Agency's Science Advisory Board regarding a research proposal entitled
"Rationale for the Planned Studies to Develop an Ambient Aquatic Life Water Quality
Criterion for TCDD" (January 1992), The Subcommittee commended EPA for its innovative
and well conceived research plan to support the development of a dioxin water criterion. The
Subcommittee endorses the body burden approach and encouraged the Agency to continue
and expand research that would validate the assumptions of the approach. The Subcommittee
found that the use of the fish, Medaka, was inherently controversial and recommended that
EPA consider either a native substitute species or modify the guidelines for developing water
quality criteria. The Subcommittee also recommended that EPA add tests to evaluate
metabolism of dioxin, develop additional biomarkers, and improve analytical measurements
and verify predicted aqueous concentrations to support the development and implementation
of the criterion. The Subcommittee found that the TEF approach was promising but
recommended further verification before it could be applied to aquatic life and wildlife.
Overall, the Subcommittee found that EPA presented several alternatives to conventional
testing of chemicals which, if verified by additional research, will provide valuable insights
about compounds that bioaccumulite and depurate slowly. This research may also lead to a
new approaches for criteria that should be reflected in the national guidelines for developing
water quality criteria.
KEY WORDS: Dioxin, Bioaecumulation, Ah receptors, TCDP, water quality criteria.
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TABLE OF CONTENTS
1. EXECUTIVE SUMMARY
2. INTRODUCTION , , . . 3
2.1 Charge for the Review , 4
2.2 Subcommittee Review Procedures . 4
3. EVALUATION OF THE RESEARCH PLAN 6
3.1 Selection of Speciei and Endpoints 6
3.2 Does the Plan fill data gaps? 7
3.3 Additional Test Recommendations *...„.. 9
3.4 Consistency with the Guidelines „ 10
3.5 Toxicity Equivalency Factor Research Needs „ 11
IV
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1. EXECUTIVE SUMMARY
The Dioxin Ecotox Subcommittee of the Ecological Processes and Effects Committee
of the Science Advisory Board (SAB) met on March 19-20, 1992 to review a draft research
plan entitled "Rationale for the Planned Studies to Develop and Ambient Aquatic Life Water
Quality Criterion for TCDD" (January 1992).
The numbers of species and endpoints are consistent with the criteria guidelines, but
the guidelines were developed for water column exposures, and the research plan under
consideration employs a body burden target. The body burden approach is logical in this
case but needs to be validated. Exposure to a single concentration using a saturated test
solution over four days, followed by exposure to dean water may not be adequate to manifest
sublethal or chronic effects comparable to standard toxicity tests. The primary problem is
one of methodological resolution.
The research plan for developing a water criterion for 2,3,7,8-TCDD is based on the
assumption that bioaccumulated dioxin is the appropriate dosing parameter and that short
term exposures which produce tissue concentrations of dioxin in organisms which correlate to
toxic effects can be used to evaluate species sensitivity. These assumptions may be correct,
but they need to be tested-
The use of the fish, Medaka, in the development of criteria is inherently controversial,
On the one hand, Medaka is a well studied model in aquatic toxicology, and the species is
suitable for many different types of assessments. However, it is not a native species to North
America. This inconsistency needs to be resolved before the Medaka data set can be
considered acceptable. Several native fish species are also suggested as substitutes for
Medaka. Further chronic studies are recommended for fish and invertebrates as well.
It is commonly believed that chemicals with very large K^s do not bioconcentrate to the
extent that the Kow would predict. There are a number of reasons for this, but the issue of
importance for TCDD is one of being confident that all of the model parameters that are used
to assess bioaccumulation and bioconcentration for this chemical are thoroughly understood.
The Subcommittee recommended that the existing measurements of K,^ be critically evaluated
to determine their adequacy.
The Subcommittee recommended that EPA conduct additional research on the role of
the intestine in dioxin effects and metabolism and evaluate other biomarkers such as
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immunosuppressors and neoplasia. They also recommended additional research on methods
to quantify dissolved water concentrations of TCDD and its dibenzoftean congeners.
FoEowing the development of the methods, they recommended field verification of the K^,
estimated concentrations.
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2. INTRODUCTION
EPA has committed to reassess the risks of 2,3,7,8-tetracMorodibenzo-p-dioxin
(TCDD or dioxin) to human health and ecosystems. Although the major public concern over
dioxin has been related to human health hazards, recent studies indicate that dioxin and
related compounds may be toxic at extremely low concentrations to reproduction of aquatic
populations in the Great Lakes. Due to this information, EPA's Duluth Environmental
Research Laboratory developed research plans "Rationale for the Planned Studies to Develop
an Ambient Aquatic Life Water Quality Criterion for TCDD" (January 1992) and a data base
to reassess the risks of dioxin and related compounds to aquatic life and wildlife.
The reassessment will result in & revised ambient aquatic life water quality criterion
for dioxin. The approach for evaluating the effects of dioxin deviates from the specific
procedures in the "Guidelines for the Deriving Numerical National Water Quality Criteria for
the Protection of Aquatic Organisms and Their Uses", hereafter referred to as guidelines for
criteria. The deviation occurs in the hazard assessment which is based on accumulation
rather than exposure concentrations and in the use of a non-native species for testing.
The Research Plan (January, 1992 draft) summarized the studies planned and on-going
and the rationale for using these studies in the reassess of criteria for aquatic life and
wildlife. The plan also included a brief list of pertinent Eterature related to the assumed
mode of action of dioxin, the occurrence of aryl hydrocarbon receptors in different taxonomic
groups, and preliminary information on reproductive effects in fish. This Research Plan wiE
contribute to a preliminary assessment of ecological risks associated with dioxin in aquatic
ecosystems.
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2.1 Charge for the Review
The SAB was asked by the Office of Water to review the research plan developed by
ORD for the revaluation of the water quality criterion for dioxin. The charge for this
Subcommittee was to review the research plans and evaluate the endpoints and test
procedures that were proposed for consistency with the National guidelines for developing
water quality and whether the suite of tests is adequate. This Subcommittee will also address
questions on the use of Toxicity Equivalent Factors that were posed to the SAB as part of the
review of the Great Lakes Water Quality Initiative. The charge for this review were as
follows:
1) Are the species and the endpoints selected appropriate?
2) Will the research plan fill the data gaps for the establishment of aquatic-based
water quality criterion?
3) Are there any other tests that should be included in the plan? If so, can the
information be gathered within the specified time frame (by the summer of 93)?
4) Are the proposed tests consistent with the Guidelines for the establishment of
water quality criteria to protect aquatic ecosystems? If not, or if there is uncertainty,
are they sufficient to develop a "scientifically defensible* water quality criterion for
use in State standards and ultimately, to develop effluent limitations?
5) What research should be undertaken to support the use of Toxicity Equivalency
Factors (TEF) for aquatic life and wildlife?
2.2 Subcommittee Review Procedures
The Subcommittee met on March 19-20, 1992 to receive briefings and review the
research plan. Oral and written public comments were received from four groups. The
research plan was characterized as a working draft, which represented both plans and studies
in progress. In response to some of the recommendations made by the panel at the review,
EPA agreed to modify its plan. In addition, the Subcommittee heard a presentation from the
Wisconsin Department of Natural Resources on their development of wildlife criteria as part
of the Great Lakes Water Quality Initiative. This panel had two members in common with
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the Great Lakes Water Quality Subcommittee which was reviewing the initiative guidance.
The final question in the charge was modified to address the concerns of the Great Lakes
Initiative as well as this dioxin research program. The Subcommittee also noted that the
approach for using TEFs with dioxin must also be consistent with the human health risk
assessment approach which is scheduled to be reviewed later.
The Subcommittee provided a summary of its preliminary findings at the conclusion
of this review and writing assignments were made at the meeting. Written materials were
compiled and edited by the Designated Federal Official and the Subcommittee Chair,
working documents were reviewed by the Subcommittee through the mail, revised and one
draft was provided to the public, EPA and the Executive Committee of the SAB at the same
time.
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3. EVALUATION OF THE SESEARCH FLAN
3.1 Selection of Spedes and Endpoints
The numbers of species and endpoints are consistent with the criteria guidelines, but
the guidelines were developed for water column exposures, and the research plan under
consideration employs a body burden target. The body burden approach is logical in this
case but needs to be validated. Exposure to a single concentration using a saturated test
solution over four days, followed by exposure to clean water may not be adequate to manifest
sublethal or chronic effects comparable to standard toxicity tests. The primary problem is
one of methodological resolution.
We applaud the program's efforts to include wildlife species which are dependent on
aquatic environments. We understand that time, cost and lack of preliminary data and
experience limit the scope of work that can be performed on avian and/or mammalian
models. However, it is important that research applied to taxa such as mink or piscivorous
birds be conducted to make the application of the criteria to wildlife species more
meaningful. The Subcommittee believes that a chronic test should be performed most likely
on mink. We encourage coordination of this aspect of the aquatic criteria program with the
Great Lakes Water Quality Initiative in its research on effects of 2,3,7,8 TCDD, especially
on minks. The program should also consider wildlife species from other regions.
Collaborative planning should make data gained from these studies valuable to both
programs.
The use of the fish, Medaka, in the development of criteria is inherently controversial.
On the one hand, Medaka is a well studied model in aquatic toxicology, and the species is
suitable for many different types of assessments. However, it is not a native species to North
America, and the National Guidelines specify the use of native species. If it is discovered
that the Medaka plays a pivotal role in the establishment of the criteria (e.g. if it were the
most sensitive species), a criterion including Medaka data would generate unfavorable public
comment. Furthermore, the data on Medaka that are presently available contain
inconsistencies (one set of larvae shows nearly perfect survival, a second set shows
significant mortality). These inconsistencies need to be resolved before the Medaka data set
can be considered acceptable. There are also some native fish species which may be useful
substitutes for Medaka,. including rainbow trout, brown bullhead, mummichog, and mangrove
rivulus. Further there are several introduced species (particularly livebearers) for which
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histopathological data are available, including the guppy, platyfish, top minnow (Poeciliopsis
sp.), and zebra danio.
The proposed research includes tests with the frog genus, Rfflg- While amphibians may
be good models for the study of developmental effects, the Agency has almost no experience
with these species. Caution should be exercised until their sensitivity and applicability for
the intended use is ascertained. Should an amphibian be used, the Subcommittee
recommends consideration of Xenopujs over Rana because there is an existing method for
determining developmental effects (i.e., the Frog Embryo Teratogenicity Assay Xenopus-
FETAX). It is recognized that Xenopus is also a non-native species and carries all the
potential problems associated with Medaka. For Xenopus. the choice can be defended
because there is already extensive scientific literature on its response to a variety of
chemicals, the test system has been independently validated in several laboratories, and
standardized protocols and an atlas of abnormalities have been developed which may facilitate
interpreting the results. In light of the previous discussion of Medaka and Xenopus. the
Subcommittee recommends that EPA consider revising the National Guidelines to allow use
of using non-native species.
Several other conclusions of the Subcommittee relative to selection of species and
endpoints are given below:
1. The Subcommittee also recommends the addition of chronic toxicity tests on a
benthic feeding fish, if it can be done within the time frame. At least one bullhead species
has shown tumors in dioxin-contaminated waters.
2. The reduced suite of invertebrate acute toxicity tests may be appropriate, but some
verification of chronic invertebrate effects should be made by conducting at least one standard
invertebrate chronic study.
3, Hie Subcommittee recommends using a freshwater bivalve for assessing
bioaccumuktion rather than the proposed snails (Aplexa hypnorum or Heliosoma sp.),
because bivalves are efficient chemical accumulators. Although effects data are limited for
dioxin, the bivalve could be an ideal organism to establish direct tissue effects of exposures
to TCDD via histopathology.
3.2. Does the Plan fill data gaps?
The research plan for developing a water criterion for 2,3,7,8-TCDD is based on the
assumption that bioaccumulated dioxin is the appropriate dosing parameter and that short
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term exposures which produce tissue concentrations of dfoxm m organisms which correlate to
toxic effects can be used to evaluate- species sensitivity. These assumptions may be correct,
but they need to be tested. The proposed research assumes that the exposure concentration
and duration of exposure are irrelevant for the production of the effect as long as the
combination of concentration and duration of exposure result in a body burden high enough
to produce the effect. It also assumes that both dietary and water exposures can be used to
derive the residue-based water quality criterion. This has never been done before and there
is only limited data which support the concept that whole body residues can be correlated
with toxic effects in a consistent manner across a range of exposure levels. The proposed
studies must demonstrate the validity of this approach by showing a strong correlation of
effects with residues and demonstrating that effects occur at the same residue level
independent of exposure route. The Subcommittee questions whether the planned four day
exposure to dioxin will be sufficient to elicit sublethal effects. Therefore, a longer exposure
may be necessary. Additionally, the validity of using laboratory-derived residue based effects
for evaluating residues in field collected species will be very difficult to demonstrate. This is
important if the approach is to have credibility and utility.
It should be pointed out that bioaccumulation is expected to occur largely in adipose
tissue. Existing theories on the mechanism of TCDD effects claim that the toxicological
effects of dioxins are largely dependent upon interactions with the aryl hydrocarbon (Ah)
receptor. There is good reason to suspect that the kinetics of dioxm with respect to the Ah
receptor would be different than those involving the storage of dioxins in lipids. Therefore,
there is good reason to expect that the proportion of dioxins reaching the Ah receptor would
be influenced by the rate at which the dioxin is administered to the organism. Without a
clear demonstration of the irrelevance of duration of exposure for effects and the
overwhelming dependence of chronic effects upon body burden, the validity of the research
program will be questionable. Toe above assumptions must be verified because they are the
linchpins upon which the residue approach is postulated lor TCDD. The Subcommittee
believes that these points are very important. Therefore, the Subcommittee recommends that
before the data and methodology are utilized in a criterion, this approach and supporting
demonstration data should be carefully reviewed since it will set a precedent for chemicals
with log K^ greater than 6.0.
It is commonly believed that chemicals with very large K^s do not bioconcentrate to the
extent that the Kow would predict There are a number of reasons for this, but the issue of
importance for TCDD is one of being confident that all of the model parameters (iiat are used
to assess bioaccumulation and bioconcentration for this chemical are thoroughly understood.
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Understanding this relationship will ultimately increase the validity of Bioaceumulation factor
(BAF) models that are based on Mpid normalization and the use of K^. In order to reduce
the error associated with this estimate an accurate measurement of the K^ is needed. It is
recommended that the existing measurements of K^ be critically evaluated to determine their
adequacy.
Understanding exposure is key to explaining dose response and bioaccumulation data.
Currently it is believed that both toxieiry and bioaccumulalion can be directly correlated with
the dissolved "free" fraction of the total chemical present in a water exposure study.
Additionally it is believed that the organic carbon content of sediments provides a
normalizing factor for calculating the bioavailable fraction of the total chemical present in
sediments from different sites. One or more of the EPA proposed BAF models that could be
used for assessing the bioaccumulation of TCDD incorporates the use of the bioavailable
(dissolved) fraction of the total TCDD present These models also normalize TCDD
concentrations to sediment organic carbon content and to organism lipid content. The
Subcommittee recommends that the mechanisms controlling bioavailability of TCDD in water
and sediment be evaluated in order to support BAF models that will be used to evaluate
TCDD environmental risk and set water quality criteria. Recent work by EPA suggests that
concentrations of organic contaminants in interstitial waters are closely related to observed
biological effects. A well defined set of experiments where residues are measured and
compared with the sorted, dissolved, and total TCDD concentrations during exposure are
appropriate. Predicted and measured residues could be compared and the theory on
bioavailability could be verified.
3.3 Additional Test Recommendations
The Subcommittee recommends that the following tests be considered for the research
plan. In some cases, they can be conducted within the time frame (spring 1993) established
for this research. These tests are in addition to the research which the Subcommittee
strongly recommends to verify the underlying assumptions of the current approach for the
dioxin criterion.
A. Biomonitoring Tests
1) The fish intestine may play an important role in the effects and metabolism
of TCDD, This tissue has an Ah receptor, induced cytochrome P-450s, and
induced EROD (7-ethoxyresoruf5n-O-deethylase) activity. Thus the intestine
and liver of fish should be assayed for the various endpoints.
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2) Other biomarkers to be considered should include
immunosuppression/immunotoxicity, preneoplastic lesions,and neoplasia.
B. Monitoring
1) At this time it does not appear possible to analytically quantitate dissolved
ambient water concentrations of chlorinated TCDD and TCDF congeners. It
does not appear impossible, however to develop the analytical methodologies to
allow for such determinations. It is recommended that the proposed research
plan be modified to include project(s) which will lead to the ability to quantify
the dissolved fraction of most hazardous chlorinated dloxios and dibenzofurans
in natural waters.
2) After development of analytical methodologies, the predicted aqueous
concentrations of TCDD should be verified by actual measurements,
3) EPA should recommend the methods by which monitoring is to be
performed. For example, should measurements in water or biota be
performed?
The development of water quality criterion will ultimately require an estimation of the
concentration in water that will produce toxic effects. The research program is totally
oriented towards developing the data needed to support the residue approach. Eventually
EPA must calculate the water concentration which should not be exceeded. Development and
verification of the model(s) that will be used are, perhaps, as important at the
bioaccumulation studies. The Agency should focus on this aspect of developing a water
quality criterion while the bioaccuniulation/toxicity studies are m progress.
3,4 Consistency with the Guidelines
The proposed use of bioaccumulated dioxins as a surrogate for dioxin exposure in water
appears to fall within the philosophy espoused by the criteria derivation process. The method
applied to dioxins does not generate a Final Acute Value (FAV) required in the National
Guidelines and therefore does not derive a Criterion Maximum Concentration (CMC). The
method only derives Criterion Continuous Concentrations (CCC) values in terms of
bioaccumulated dioxin concentrations in aquatic biota. The derivation of the CCC is
complicated by the fact that the species sensitivity appear to be dichotomously distributed
between sensitive and insensitive species. This can seriously distort the derivation of the 5th
percentile downward if regression techniques are applied.
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With the existing inability to measure aqueous environmental levels of TCDD and our
resulting ignorance of its partitioning in the environment, the criteria, will not lead to
scientifically defensible effluent limits. Typical effluent limits for water soluble chemicals
with low hydrophobicity directly apply water quality criteria for receiving waters into
permits. The proposed criteria development method for TCDD will result in aquatic life
tissue residue concentration above which ecological effects could occur. There is great
uncertainty in "back" calculating a residue concentration into an ambient water concentration.
Such a calculation would need to be specific for species to be protected and as mentioned
previously, would require an accurate measurement of dissolved TCDD. There would be
site-specific consideration for species which would require lipid normalization of the criteria,
adjustment for K« (transfer front sediment) and consideration for route of exposure to "fish".
The process by which the residue-based criteria would be applied to an effluent discharge is
uncertain and EPA is requested to carefully consider and propose/develop a workable
procedure. The existing bioaccurnulation models available for calculating an ambient water
concentration need further peer review and testing before they will be defensible.
The "National Guidelines" require all collected data to be evaluated for minimum
acceptability before inclusion in data bases for criteria development. The procedures for
"collection of data" (p.21-22) set acceptability requirements. EPA should comply with these
criteria in TCDD criteria development. Under such constraints, they should be aware that
some data presented at the briefing would have been rejected.
The documentation for much of the proposed research is based on previous work done
at the Duluth Environmental Research Laboratory. Since many of the proposed efforts will
take place at the same laboratory and will be performed by some of the same investigators,
some may question whether the program is too provincial and whether its hypotheses have
received peer review. The Subcommittee therefore recommends that every effort be made to
include peer reviewed references and documentation from other researchers (both academic
and stakeholders) which are pertinent to the development of dioxin criteria and its research
plan.
3,5 Toxicity Equivalency Factor Research Needs
The TEF approach appears promising but it must be investigated further. TheTEF
data obtained for lake trout eggs suggest that this approach may work for aquatic species and
that the values are different than values calculated by Safe (1990). Whole organism TEF or
at least target organ TEF with species of interest (birds, mammals, fish) may be the best way
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to use the TEF. However, a cause and effect relationship between blue sac disease and
TCDD was not adequately demonstrated by the data presented. Blue sac disease appears to
be a general stress syndrome that can be caused by 20 specific causes, including, infectious
physiological genetic and physico-chemical agents. The Subcommittee strongly recommends
that the effect with TCDD be verified with appropriate bloodstock replication.
For TEF to be used for aquatic life and wildlife, more studies are needed to show
phylogenetic variability. An assumption is made that a similar Ah receptor in various animal
groups is responsible for various biological effects observed in fish. Also, the assumption is
made that metabolism of dioxiit is of little importance in isfiu The activated complex
(dioxin-Ah receptor) translocating protein in the cell nucleus induces the production of certain
cytochrome P^SOs. Certain electrophilic metabolites of dioxin produced by the induced P-
450 are thought to initiate cancer. This brings up the question, are the reproductive effects
of dioxin in fish due to dioxin or to dioxin metabolites? Are fish quite different with respect
to metabolism of dioxin than other wildlife?
At present the Subcommittee concludes that there are insufficient data available to
judge the reliability and accuracy of the proposed TEF approach. Perhaps the question can
be evaluated more fully in combination with the ORD report on the effects of TCDD on
human health in another SAB review.
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