United States
Environmental Protection
Agency
EPA/625/3-87/012
March 1987
Interim Procedures for
Estimating Risks
Associated with
Exposures to
Mixtures of
Chlorinated Dibenzo-
p-Dioxinsand
-Dibenzofurans
(CDDsand CDFs)
RISK ASSESSMENT FORUM
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Interim Procedures for Estimating Risks
Associated with Exposures to Mixtures of
Chlorinated Dibenzo-p-Dioxins and
-Dibenzofurans (CDDs and CDFs)
October 1986
Authors
Judith S. Bellin, Ph.D.
Office of Solid Waste and Emergency Response
Donald G. Barnes, Ph.D.
Office of Pesticides and Toxic Substances
Technical Panel
Co-Chairmen: Donald G. Barnes (OPTS)
Hugh L. Spitzer(ORD)
Steven Bayard, Ph.D. (ORD) Paul Milvy, Ph.D. (OPPE)
Irwin Baumel, Ph.D. (OPTS) Abe Mittelman, M.S. (OSWER)
Judith Bellin, Ph.D. (OSWER) Debdas Mukerjee, Ph.D. (ORD)
David Cleverly, M.S. (OAQPS) Charles Nauman, Ph.D. (ORD)
Frank Gostomski, Ph.D. (ODW/OWRS) Jerry Stara, Ph.D., D.V.M. (ORD)
Charalingayya Hiremath, Ph.D. (ORD)
Risk Assessment Forum Staff
Dorothy E. Patton, Ph.D., J.D., Executive Director
Risk Assessment Forum
U.S. Environmental Protection Agency
Washington, DC 20460
US Em'iropr-.er.tal Protection Agency
230 South Dearborn Street'
Chicago, Illinois 60604 -'
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Disclaimer
This document has been reviewed in accordance with U.S. Environmental
Protection Agency policy and approved for publication. Mention of trade names
or commercial products does not constitute endorsement or recommendation
for use.
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Contents
Page
List of Tables iv
Peer Review v
Science Advisory Board Review vi
Preface vii
I. Summary 1
II. The Need for a Procedure for Assessing the Risk Associated with
Exposure to Complex Mixtures of CDDs and CDFs 4
III. Approaches to Hazard Assessment for CDD/CDF Mixtures ...; 5
A. The Ideal Approach—Long-Term, Whole-Animal Toxicity
Assay of Mixtures 5
B. A Promising Approach—Short-Term, Biological Assay of
Mixtures 5
"V^
C. A Reductionist Approach—Additivity of Toxicity of
u Components 5
D. An Interim Approach—2378-TCDD Toxicity Equivalence
Factors (TEFs) 6
IV. The 2378-TCDD Toxicity Equivalence Factors (TEFs) Approach to
Assessing the Toxicity of Complex Mixtures of CDDs and
CDFs 7
V. Applications to Risk Assessment 13
VI. Comparison of the TEF Approach with Results of Biological
Testing 22
VII. Research Needs 24
References 25
Appendix A: Nomenclature A-1
Appendix B: Comparison of Different Approaches to Calculating
2378-TCDD Equivalents B-1
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List of Tables
Number Page
1. Some Approaches to Estimating Relative Toxicities of
PCDDs and PCDFs 2
2. Potencies of Dioxins Relative to 2,3,7,8-TCDD 9
3. CDD/CDF Isomers of Most Toxic Concern 11
4. PCDs/PCDFs in Some Environmental Samples 14
5. Use of the TEF Approach 17
B-1. Relative 2378-TCDD Equivalents B-2
B-2. Calculation of 2378-TCDD Toxicity Equivalents for St. Louis
Air Particulates Using Homologue-Specific Data B-3
B-3. Calculation of 2378-TCDD Toxicity Equivalents for PCB Fire
Soot Using Isomer-Specific Data B-4
B-4. Calculation of 2378-TCDD Toxicity Equivalents for
MSW ESP Dust Using Homologue-Specific Data and
2378-TEFs B-6
B-5. Calculation of 2378-TCDD Toxicity Equivalents for Lake
Sediment Using Homologue-Specific Data B-7
B-6. Calculation of 2378-TCDD Toxicity Equivalents for Milorganite
Using Homologue-Specific Data B-9
B-7. Calculation of 2378-TCDD Toxicity Equivalents for Oslo
MSW Fly Ash Using Homologue-Specific Data B-10
B-8. Calculation of 2378-TCDD Toxicity Equivalents for Ontario
MSW Fly Ash Using Homologue-Specific Data B-12
B-9. Calculation of 2378-TCDD Toxicity Equivalents for MSW
at Japanese Plant A Using Homologue-Specific Data B-13
B-10. Calculation of 2378-TCDD Toxicity Equivalents for MSW
at Japanese Plant B Using Homologue-Specific Data B-15
B-11. Calculation of 2378-TCDD Toxicity Equivalents for MSW
at Albany Using Homologue-Specific Data B-16
B-12. Calculation of 2378-TCDD Toxicity Equivalents for WP
AFB (Best) Using Homologue-Specific Data B-18
B-13. Calculation of 2378-TCDD Toxicity Equivalents for WP
AFB (Worst) Using Homologue-Specific Data B-19
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External Peer Review
The following External Peer Reviewers have reviewed and commented
on an intermediate draft of this report.
Dr. Renate Kimbrough
Centers for Disease Control
Dr. John F. Gierthy
New York State
Department of Health
Dr. Alan Poland
McArdle Laboratory for
Cancer Research
Dr. Richard Kociba
Dow Chemical Company
Dr. Barry Commoner
CBNS Queens College
New York
Dr. Ellen K. Silbergeld
Environmental Defense Fund
Dr. Brendan Birmingham
Ministry of Environment
Toronto, Ontario
Dr. Martin Boddington
Priorities Issues Directorate
Environment Canada
Dr. Stephen Safe
Texax A & M University
Dr. Linda Birnbaum
National Institute of
Environmental Health Sciences
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U.S. Environmental Protection Agency
Science Advisory Board Review
The Dioxin Equivalency Subcommittee of the USEPA Science Advisory
Board has reviewed and commented on the final draft of this report.
Dr. Allan Okey
The Hospital for Sick Children
Toronto, Ontario
Dr. Nancy Kim
New York State Bureau of
Toxic Substances Management
Dr. Ellen K. Silbergeld
Environmental Defense Fund
Dr. Stephen Safe
Texax A & M University
Dr. Richard Griesemer, Director
Oak Ridge National Laboratory
Dr. Linda Birnbaum
National Institute of
Environmental Health Sciences
Dr. Robert Huggett
Virginia Institute of Marine Science
College of William and Mary
Terry F. Yosie, Director
USEPA Science Advisory Board
Dr. Tom Gasiewica
University of Rochester
Medical Center
Dr.Robert Neal*
Chemical Industry
Institute of Toxicology
Dr. Patrick Durkin
Syracuse Research Corporation
'Did not attend the Science Advisory Board Meeting
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Preface
As part of its effort to address risks posed by chlorinated dibenzo-p-dioxins
and chlorinated dibenzofurans (CDDs and CDFs) in the environment, the
U.S. Environmental Protection Agency (EPA) has adopted an interim
procedure, based on dioxin "toxicity equivalence" factors (TEFs), for
estimating the hazard and dose-response of complex mixtures containing
CDDs and CDFs in addition to 2,3,7,8-TCDD. The TEF procedure, and the
scientific data upon which it is based, are the subject of this report.
This report, which has been extensively reviewed by EPA and external
(non-EPA) experts, was prepared for EPA's Risk Assessment Forum (Forum)
and was approved by the EPA Risk Assessment Council in August 1986.
In September 1986, the report was reviewed by a special Subcommittee
of the Agency's Science Advisory Board (SAB), a congressionally mandated
body of independent scientists.
The SAB Subcommittee concurred with EPA's view that the TEf method
is a reasonable interim approach to assessing the health risks associated
with exposure to mixtures of CDDs and CDFs for risk management purposes.
They noted that the method proposed may lack scientific validity and agreed
with EPA on the importance of efforts to validate the method by selected
experimental testing of hypotheses. The Agency received strong encourage-
ment to continue research on other approaches to estimating risks for
substances in mixtures. The Subcommittee also indicated that it was
important that the interim approach be re-evaluated systematically by EPA
as lessons are learned from toxicologic research and from application. Lastly,
the group cautioned that the interim TEF method should be largely reserved
for special situations where the components of the mixture are known, where
the composition of the mixture is not expected to vary much with time, and
where the extrapolations are consistent with existing animal data. Some
aspects of the report have been revised to take the Subcommittee's comments
into account.
These SAB comments reinforce EPA's views on the strengths and
limitations of the TEF approach. Throughout development of the report, EPA
scientists have emphasized that the TEF approach is an interim science policy
to be used pending development of more rigorous and scientifically robust
approaches, some of which are mentioned in the report. The Agency intends
to encourage and to pursue a range of research activities which will both
further test the hypotheses that underlie this interim procedure and lead
to alternative, more direct approaches to determining the toxicity of CDD
and CDF mixtures.
Research on CDDs and CDFs continues at a rapid pace, and the Agency
is closely monitoring changes in the data base upon which the TEF approach
has been established. Through an annual updating of the approach, the Forum
will assure that TEF factors remain current with the existing animal data.
The TEF procedure will be used generally throughout the Agency for
situations in which the components of the mixture are known (or can be
reasonably anticipated) and where the composition is not expected to vary
greatly with time.
On other issues the SAB Subcommittee and other peer reviewers
recommended that EPA consider more explicitly the effects of pharmaco-
dynamics (the bioavailability, absorption, distribution, metabolism, and
elimination) of relevant environmental mixtures in whole animals when
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assigning TEFs to the homologues and isomers of CDDs and CDFs. For
example, studies suggest that higher chlorinated CDDs and CDFs are less
likely to be absorbed during acute exposures. Further, some CDDs and CDFs
are more likely to be metabolized and eliminated than are others. The Forum
will review these issues and recommend changes in some TEFs, as
approporiate.
In summary, the TEF approach provides a useful interim method for
consistently interpreting the significance of CDD and CDF residues in the
environment, until more direct methods are available. Users should be aware
of the uncertainties associated with the procedure. In addition to the
uncertainties inherent in the 2,3,7,8-TCDD quantitative risk assessment,
which the TEF approach implicitly adopts, the approach includes the added
qualitative assumption that the other CDDs and CDFs will demonstrate the
same chronic effects as 2,3,7,8-TCDD. While there are good scientific reasons
to expect this to be the case, the data to support this assumption are limited.
The Agency plans to update the TEFs on a regular basis, incorporating
additional information as it becomes'available so that the approach will reflect
the best current scientific thinking. The intent is to replace this interim
procedure with a more rigorous approach as research results permit.
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I. Summary
The U.S. Environmental Protection Agency (EPA) is often confronted with
the need to determine the risks associated with exposure to materials such
as soot, incinerator fly ash, industrial wastes, and soils which contain complex
mixtures of chlorinated dibenzo-p-dioxins (CDDs) and chlorinated dibenzo-
furans (CDFs).1 Recognizing the public and toxicological concern generated
by these chemicals and the significant gaps in our ability to evaluate the
human health potential of these compounds by existing procedures, the CDD/
CDF Technical Panel of the Risk Assessment Forum (Forum) is recommending
an interim method to aid in the assessment of the human health risks posed
by mixtures of CDDs and CDFs until data gaps are filled.
The Technical Panel has reviewed a spectrum of approaches for making
such assessments, consistent with EPA's Guidelines for the Health Risk
Assessment of Chemical Mixtures, and has concluded that a direct biological
assessment of the toxicity of complex mixtures of CDDs and CDFs is preferred.
However, a validated bioassay that can plausibly be applied to such mixtures
is not now available, although promising research is in progress in the area.
An alternative approach involves explicit analysis and toxicological
determination of each of the constituent CDD/CDF congeners. The data
required for such an approach also need to be developed and are not likely
to be generated soon. The Forum therefore concludes that, as an interim
science policy measure, a reasonable estimate of the toxic risks associated
with a mixture of CDDs and CDFs can be made by taking into account the
distribution of CDD/CDF congeners or homologues and the likely relative
toxicity of these compounds. This document describes the recommended
interim procedure for generating the "2378-TCDD equivalence" of complex
mixtures of CDDs and CDFs, based on congener- or homologue-specific data,
and for using such information in assessing risk. (The recommendations
are summarized in the rightmost column of Table 1.)
The Forum acknowledges that this procedure is not based on a thoroughly
established scientific foundation. Instead, the approach represents a
consensus recommendation for interim science policy, subject to change
as additional data are available. The approach is judged to be applicable
to mixtures of CDDs and CDFs, but should not be construed as being applicable
as well to mixtures of other chemicals.
The basis of this approach, i.e., the assignment of toxicity equivalence
factors (TEFs) is subject to revision as new scientific data become available
in the future. Consequently, risk assessors and risk managers are urged
to use informed discretion, noting specific problems on a case-by-case basis,
when applying the procedure to any particular situation. The Forum urges
the support of research to test further the hypotheses that underlie this
interim procedure and to develop the preferred approaches.
1See Appendix A for the nomenclature and conventions used in this paper.
1
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Table 1. Some Approaches to Estimating Relative Toxicities of PCDDs and PCDFs
Basis/
compound
(Basis)
Mono thru di CDDs
Tri CDDs
2378-TCDD
other TCDDs
2378-PeCDDs
other PeCDDs
2378-HxCDDs
other HxCDDs
2378-HpCDDs
other HpCDDs
OCDD
2378-TCDFs
other TCDFs
2378-PeCDFs
other PeCDFs
Swiss3
Enzyme
0
0
1
0.01
0.1
0.1
0.1
0.1
0.01
0.01
0
0.1
0.1
0.1
0.1
Grant"
Oliec
Commonerd
0
0
1
1
0.1
0.1
0.1
0.1
0.1
0.1
0
0.1
0.1
0.1
0.1
New
York
State8
LDso
0
0
1
0
1
0
0.03
0
0
0
0
0.33
0
0.33
0
Ontariof
Various
effects
0
1
1
0.01
1
0.01
1
0.01
1
0.01
0
0.02
0.0002
0.02
0.0002
FDAS
Various
effects
0
0
1
0
0
0
0.02
0.02
0.005
0.005
<0.00001
0
0
0
0
CAh
0
0
1
0
1
0
1
0
1
0
1
1
0
1
0
EPA1
1981
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
EPA
current
recommend.
Various
effects
0
0
1
0.01
0.5
0.005
0.04
0.0004
0.001
0.00001
0
0.1
0.001
0.1
0.001
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Table 1. (continued)
Basis/
compound
(Basis)
2378-HxCDFs
other HxCDFs
2378-HpCDFs
other HpCDFs
OCDF
Swiss3
Enzyme
0.1
0.1
0.1
0
0
Grant"
Oliec
Commoner*1
0.1
0.1
0.1
0.1
0
New
York
State"
l-Dso
0.01
0
0
0
0
Ontario1
Various
effects
0.02
0.0002
0.02
0.0002
0
FDA9
Various
effects
0
0
0
0
0
CAh
1
0
1
0
0
EPA1
1981
0
0
0
0
0
EPA
current
recommend.
Various
effects
0.01
0.0001
0.001
0.00001
0
"Swiss Government, 1982.
"Grant, 1977.
°Olie et a/., 7983.
dCommoner et a/., 7984.
"Eadon et a/., 7982.
fOntario, 1982.
9L/.S. DHHS, 7983.
hGravitz et a/., 7983.
EPA, 1981.
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II. The Need for a Procedure for Assessing the
Risk Associated with Exposure to
Complex Mixtures of CDDs and CDFs
During the late 1970s, the Agency was faced with assessing the human
health significance of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin
(2,3,7,8-TCDD). In preparation for the cancellation hearings for the herbicides
2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and Silvex, the Agency generated
risk assessments for several toxic responses for 2,3,7,8-TCDD. The
quantitative cancer risk assessment developed by the Carcinogen Assessment
Group was later adapted for use in the Water Quality Criteria (WQC) Document
for 2,3,7,8-TCDD (U.S. EPA, 1984a). In addition to carcinogenicity concerns,
the WQC document contains an assessment of systemic toxicity based on
reproductive effects resulting from exposure to 2,3,7,8-TCDD.
Later, it became clear that exposure situations exist in the country which
involve more than 2,3,7,8-TCDD alone. Data on emissions from combustion
sources (e.g., hazardous waste and municipal waste incinerators) and
contents of waste from certain industrial production processes indicate that
the majority of the 75 CDDs and 135 CDFs can be detected in the environment.
In recent years, the reporting of at least homologue-specific data for the
CDDs and CDFs has become commonplace, and the Agency has taken some
steps to address the significance of these findings. For example, the Health
Assessment Document for Polychlorinated Dibenzo-p-Dioxins, prepared for
the Office of Air Quality Planning and Standards (U.S. EPA, 1985b), contains
a quantitative risk assessment for a mixture of hexachlorodibenzo-p-dioxins
(HxCDDs) based on carcinogenicity studies conducted by the National Cancer
Institute. These concerns have also led to regulatory action; e.g., several
industrial wastes containing tetra-, penta-, and hexa-chlorodioxins, and
-dibenzofurans were recently designated by the Agency as EPA hazardous
wastes.
Faced with increasing amounts of isomer- and homologue-specific data,
and recognizing the significant potency and structure-activity relationships
exhibited in in vivo and in vitro studies of CDDs and CDFs, the Technical
Panel perceives a need to address more generally the potential risks posed
by the congeners other than 2,3,7,8-TCDD and the mixture of HxCDDs.2
Detailed consideration of the toxicity of the vast majority of the CDDs and
CDFs is limited by the lack of a complete lexicological data base on most
of the congeners. Further, it is unlikely that many long-term test results
will be availabale soon. For example, research on 2,3,7,8-TCDD has been
under way for more than two decades at an estimated cost of more than
one hundred million dollars. Although this chemical has been investigated
to a much greater extent than any of the other CDDs and CDFs, unanswered
questions remain. Therefore, the Forum believes that an interim science
policy position should be adopted for use in assessing risks associated with
CDD/CDF mixtures, until more definitive scientific data are available.
2ln the early 1980s, the Agency developed a method for an approximate assessment of the risks
of the emission of CDDs and CDFs associated with the high-temperature incineration of PCBs
and combustion of municipal waste (U.S. EPA, 1981; U.S. EPA, 1982); see Table 1. The procedure
presented in this document is a refinement of that approach. A comparison of a variety of methods
is included in Appendix B
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III. Approaches to Hazard
Assessment for CDD/CDF Mixtures
A. The Ideal Approach—Long-Term, Whole-Animal Toxicity
Assay of Mixtures
Under ideal conditions, an assessment of the toxicity of a mixture of
chemicals is best accomplished by direct evaluation of its toxic effects, e.g.,
by determining the effects of chronic exposure in an experimental animal
(U.S. EPA, 1985a). Such an assessment is time-consuming and costly and
would theoretically have to be performed for each of the many mixtures
of environmental importance. Therefore, this idealized approach would cause
unacceptable delays in addressing the potential health risks associated with
exposures to CDD/CDF mixtures.
Long-term animal studies might be considered for some categories of CDD/
CDF sources which have characteristic compositions; e.g., emission from
some combustion sources. However, the need for an interim approach would
remain.
B. A Promising Approach—Short-Term. Biological Assay of
Mixtures
An alternative, and perhaps more achievable, approach to hazard
assessment of a mixture is a short-term assay (in vivo or in vitro) that indirectly
provides a measure of the mixture's potential toxicity. In the case of mixtures
containing CDDs and CDFs, short-term assays are under development that
directly determine the 2,3,7,8-TCDD-like response which could be used as
a measure of the toxicity of the mixture as a whole. Such assays take
advantage of the similar toxic end points induced by CDDs and CDFs, and
have been used to assess the potential health hazards of exposure to CDD/
CDF-contaminated soot from PCB fires (Eadon et al., 1982; Gierthy and Crane,
1984; Gravitz et al., 1983), and for predicting the potential toxicity of
incinerator fly ash (Rizzardini et al., 1983; Sawyer et al., 1983).
Although the development of such "mixture assays" is progressing rapidly
(e.g.. Safe et al., 1985), additional work is required to more fully validate
the assay findings for specific toxic end points, especially chronic effects,
and aspects of pharmacokinetics need to be considered. The Forum,
recognizing the importance of short-term assays, encourages research in
this area.
C. A Reductionist Approach—Additivity of Toxicity of
Components
In the absence of a fully developed "mixture assay," the components in
a mixture of CDDs and CDFs could theoretically be identified and quantified
by analytical chemists. Then the toxicity of the mixture could be estimated
by adding the toxicity contributed by each of its components. In the case
of most environmental mixtures, however, this method would be of limited
value since congener-specific analyses for the 75 CDDs and 135 CDFs
potentialy present in the mixture are seldom available. In addition, there
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is little informmation available on the toxic potency of most of these
congeners. Therefore, this approach is not viable at this time; nor is it likely
to be feasible in the near future.
D. An Interim Approach—2378-TCDD Toxicity Equivalence
Factors (TEFs)
The Forum recommends a fourth alternative for estimating the risks
associated with exposure to complex mixtures of CDDs and CDFs. In this
approach, as in approach C above, information is obtained on the
concentrations of homologues and/or congeners present in the mixture.
Then, using the available toxicological data and reasoning on the basis of
structure-activity relations, the significance of the exposure to each of the
components is estimated and expressed as an "equivalent amount of 2378-
TCDD." Combining this information with hazard information on 2,3,7,8-TCDD,
and assuming additivity of effects, the risks associated with the mixture of
CDDs and CDFs can be estimated if exposure is known. Key to the approach
are the 2378-TCDD Toxicity Equivalence Factors (TEFs) which are derived
in Section IV.
The general approach using TEFs as outlined here is not unique; several
organizations have used similar approaches (see Table 1).
At one extreme, all CDDs and CDFs could be assumed to be as toxic as
2,3,7,8-TCDD (all TEFs = 1). This position is not recommended since the
limited long-term data (2-year cancer bioassays) on 2,3,7,8-TCDD and a
mixture of 2378-HxCCDs (and the greater body of short-term data on many
CDDs and CDFs) indicate that such an assumption is overly conservative.
At the other extreme one could totally ignore the presence of CDDs and
CDFs other than those for which adequate long-term data are available (most
TEFs = 0). This position is not recommended in light of the similar toxic
properties of several of these compounds and the structure-activity
relationship demonstrated for effects resulting from less than lifetime
exposures.
Instead, the Forum recommends that the TEF procedure presented in
Section IV be adopted as a matter of science policy on an interim basis,
subject to revision as new experimental data become available. Based on
the available scientific information, the Forum believes that this approach
represents an appropriate means of approximating the potential risk of
exposure to mixtures of CDDs and CDFs for purposes of risk management.
The approach will enable the Agency to deal with many, but not all, of
its problems; e.g., assigning priority to Superfund sites, estimating the extent
to which a hazardous waste site should be cleaned up, guiding decisions
on which manufacturing wastes can be delisted as EPA hazardous wastes,
and estimating risks associated with the emission of CDDs and CDFs from
combustion sources.
The remainder of this document discusses the TEF approach in greater
detail, illustrates its use in risk assessment, and identifies additional research,
the results of which would provide information for adjustments to this interim
approach.
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IV. The 2378-TCDD Toxicity Equivalence Factors
(TEFs) Approach to Assessing the Toxicity of
Complex Mixtures of CDDs and CDFs
2,3,7,8-TCDD is one of 75 CDDs. Exceptionally low doses of this compound
elicit a wide range of toxic responses in many animals, e.g., adverse
reproductive effects, thymic atrophy, and a "wasting syndrome" leading to
death. Although the Agency prefers definitive human evidence when
assessing the potential human carcinogenicity of chemicals, such data are
rarely available and are lacking in the case of CDDs and CDFs period. However,
EPA's Carcinogen Assessment Group (CAG) has determined that, based on
demonstrated effects in animals, there is sufficient evidence to regard 2,3,7,8-
TCDD and a mixture of two 2378-HxCDDs as probable human carcinogens.
The CAG quantitative assessment indicates that these chemicals are among
the most potent animal carcinogens evaluated by the Agency to date. Limited
data suggest that some of the other CDDs may have other toxic effects similar
to those of 2,3,7,8-TCDD, again at very low doses.
Moreover, these toxicity concerns are not restricted to CDDs. Limited
experimental data, supplemented by structure/activity relationships in in vitro
tests that are correlated with in vivo toxic effects of CDFs, indicate that
some of these compounds exhibit "2,3,7,8-TCDD-like" toxicity (Bandiera et
al., 1984; Okey et al., 1984; Safe et al, 1985).
The biochemical mechanisms leading to the toxic response resulting from
exposure to CDDs and CDFs are not known in detail. However, experimental
data have accumulated which suggest that an important role in the
development of systemic toxicity resulting from exposure to these chemicals
is played by an intracellular protein, the Ah receptor, the putative product
of a gene locus designated Ah. This receptor binds halogenated polycyclic
aromatic molecules, including CDDs and CDFs. It has been postulated that
the Ah locus controls several pleiotropic responses: a limited, but widely
expressed gene complex that includes the structural genes for aryl
hydrocarbon hydroxylase (AHH) expression, and, in a few organs, such as
skin and thymus, a second gene complex regulating cell proliferation and
differentiation (Knutson and Poland, 1980; Neal et al., 1982; Greenlee et
al.., 1985a).
In several mouse strains, the expression of toxicity of 2,3,7,8-TCDD-related
compounds, including cleft palate formation, liver damage, effects on body
weight gain, thymic involution, and chloracnegenic response, has been
correlated with their binding affinity for the Ah receptor, and with their ability
to induce several enzyme systems, some of which have been linked to the
expression of carcinogenicity (Poland and Knutson, 1982; Bandiera et
al.,1984; Madhukar et al., 1984; Poland et al., 1985; Safeetal., 1985; Vickers
et al., 1985). Structure-activity studies also link the enhanced in vitro cell
differentiation caused by these compounds to the presence of the Ah receptor
(Greenlee et al., 1985b).
However, it has also been noted that the cytosolic receptor binding alone
may not be the sole determinant of the capacity for AHH induction (Neal,
1985; Okey and Vella, 1984). In interspecies comparisons there are poor
correlations between the concentration of cellular Ah receptor, its ability
to bind 2,3,7,8-TCDD and AHH induction (Denison and Wilkinson, 1985;
Gasiewicz and Rucci, 1984; Neal, 1985); and in the mouse the development
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of TCDD-induced liver toxicity cannot be ascribed solely to the presence of
the Ah receptor (Greig et al., 1984).
A recent review concludes that although there are inconsistencies across
species in the Ah receptor's being the sole mechanism of toxicity of CDDs
and CDFs, the data suggest that the binding of these compounds to the
receptor is in some way related to some of the biological effects seen in
experimental animals (Neal, 1985).
Table 2 summarizes information on a variety of end points elicited by CDOs
and CDFs: acute toxicity, carcinogenicity, reproductive effects, receptor,
binding, enzyme induction, and in vitro cell transformation. For ease of
comparison, the data are normalized to unity for 2,3,7,8-TCDD. For example,
2378-HxCDDs have about 5% the Ah receptor binding strength of 2,3,7,8-
TCDD. Their reproductive toxicity and carcinogenic potency are, respectively,
about 1% and 4% that of 2,3,7,8-TCDD. Kociba and Cabey (1985) recently
presented similar data.
The structure/activity generalizations based on the data in Table 2 support
the generalizations in the literature concerning the congeners that are most
likely to be of toxic concern (Poland and Knutson, 1982; Gasiewicz and Rucci,
1984; Bandiera et al., 1984). That is, congeners that are substituted in the
lateral 2,3,7 and 8 positions are likely to exhibit toxic effects at lower doses
than other congeners. This includes the 15 tetra-, penta-, hexa- and
heptachlorinated CDDs and CDFs listed in Table 3.3
The "2378-TCDD equivalence factors" (TEFs) listed in Tables 1 and 3 were
assigned using several criteria.
1. Definitive data on human carcinogenicity.
2. In the absence of definitive data on human carcinogenicity, information
on carcinogenic potency is based on long-term animal studies which
takes precedence over any other data.
3. When carcinogenic activity has not been demonstrated, data on
reproductive effects become determinative because of the significance
of this end point In humans. In addition, the estimated exposure levels
potentially resulting in reproductive and carcinogenic effects are similar.
4. When neither carcinogenic nor reproductive effects have been
demonstrated, the weight of the evidence of the in vitro test data is
estimated. To simplify the approach and to acknowledge the
approximate nature of the approach, these estimates are rounded off
to the nearest order of magnitude. Somewhat more weight is placed
on data from receptor binding interaction and oxidative enzyme
3The Technical Panel is aware that some investigators (e.g.. Grant, 1977; Olie et al., 1983;
Commoner et al., 1984; and Ontario, 1982, 1984) have broadly defined congeners of concern
to include those tri- to hepta- congeners which are substituted with at least three chlorines
in the four lateral (2, 3, 7, and 8) positons. The toxicity data (Table 2) do not strongly support
this extended range of concern Further the increased level of complexity invoked by including
these additional congeners suggests a greater level of accuracy and resolution than the Technical
Panel believes is presently warranted by the TEF approach.
The Technical Panel is also aware that receptor binding data suggest a relatively high potential
toxicity for 1,2,4,6,7-PeCDF. Examination of stereochemical models shows that the 4 and 6
positions of CDFs exhibit partial overlap with the lateral chlorine groups of 2,3,7,8-TCDD (Bandiera
et al., 1984). However, this increased receptor binding activity is not reflected in an increased
potency of 1,2,4,6,7-PeCDF as an enzyme inducer (see Table 2), an end point which has been
shown to correlate with subchronic toxicity (Safe et al., 1985). Therefore, the Technical Panel
is treating 1,2,4,6,7-PeCDF as a "non-2378-congener" at this time; however, additional data
could lead to a change in this position
1,2,3,6,7- and 2,3,4,6,7-PeCDF are almost as potent as 2378-PeCDF in the induction of AHH
activity in human lymphoblastoid cells in vitro (see Table 2). However, because this assay seems
to yield relative potencies that do not agree with other short-term tests, and because dose-
response data are not available for this assay, these data are not included in the overall evaluation
at the present time.
8
-------
Table 2. Potencies of Dioxins Relative to 2,3,7,8-TCDD
Chemical
CDDs:
Mono thru tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDDs
HxCDDs
2378-HpCDDs
HpCDDs
OCDD
CDFs:
Mono thru tri
2378-TCDF
Guinea
pig
< 70-48
7a
<.001a
.67*
.002"
.03"
.004"
.002"
—
—
.28; .5"
Reproductive/
Care/no- teratogenic Receptor
genicity effects binding
.001:01"
•jb 70,1 70
<.007* <.01-.16e
1"
.04b .01C .05"
—
<.00001k
X.001-.02**
.03-.1 3'-" .3"; .24"; .4'
Enzyme Induction
AHH EROD
Animal Human
cells cells
<.001f
1* 1" 19
<.001-.029
.02:29
.001:19
.002:0049-' —
<.001f
<.001f
<.001d <.001d
.01-.4W" .4™ .7"
Flat
(XB) Immuno-
Cell cell toxicity
keratin. assay in vitro
.01" — .005"
7» 77 i°,p
<.001-.01" —
__-58 :: ::
.005e __
—
—
.0078 __
.05" .1' .1°, 1P
-------
Table 2. (continued)
Enzyme Induction
Guinea
pig
Chemical LDso
TCDFs
2378-PeCDF
12467-PeCDF
PeCDFs
3 2378-HxCDFs .017"
HxCDFs
2378-HpCDFs
HpCDFs
Reproductive/
Care/no- teratogenic Receptor
genicity effects binding
.001-.05d'»
.13d; .7"; .6h
.75"
.001-.1d-e
.04-.5»>h
.0019-h
<.001h
AHH
Animal
cells
<.007d; .04m
<.3d; .4m
.002h
<.001-2d-"-m
.05-.2h-m
.001m;.002h
.0043
<.001f
Human
cells
jm
gm
gm
.9m
—
EROD
Cell
keratin.
<.005d
.1"
<.001h
<.007h
.7-.5"
.006"
— —
Flat
(XB)
cell
assay
—
—
—
—
—
Immuno-
toxicity
in vitro
—
—
—
—
—
"McKinney and McConnell, 1982; Moore et a/., 7979.
bU.S. EPA, 1984a.
cMurray et at., 1979; Schwetz et al., 1973;
Weber et al., 1984.
dBandiera et al., 1983.
"Knutson and Poland, 1980.
'Bradlaw et al., 1979.
"Bradlaw et al., 1980.
hBandiera et al., 1984.
'Hassoun et al., 1984.
'Gierthy and Crane, 1985.
"Weber et al., 1984.
'Poland et al., 7979.
mNagayama et al., 1985a,b.
"Poland et al., 1976.
"Dencker et al., 1985.
PQreenlee et al., 1985b.
-------
Table 3. CDD/CDF Isomers of Most Toxic Concern*
Dioxin
Isomer
2,3,7,8-TCDD
1,2,3,7,8-PeCDD
1,2,3,4,7,8-HxCDD
1,2,3,7,8,9-HxCDD
1,2,3,6,7,8-HxCDD
1,2,3,4,6,7,8-HpCDD
TEF"
1
0.5
0.04
0.04
0.04
0.001
Dibenzofuran
Isomer
2,3,7,8-TCDF
1,2,3,7,8-PeCDF
2,3,4,7,8-PeCDF
1,2,3,4,7,8-HxCDF
1,2,3,7,8,9-HxCDF
1,2,3,6,7,8-HxCDF
2,3,4,6,7,8-HxCDF
1,2,3,4,6,7,8-HpCDF
1,2,3,4,7,8,9-HpCDF
TEF"
0.1
0.1
0.1
0.01
0.01
0.01
0.01
0.001
0.001
"In each homologous group, the relative toxicity factor for the isomers not
listed above is 1/100 of the value listed above.
bTEF = Toxicity Equivalence Factor = relative toxicity assigned.
induction, due to the correlations between these in vitro end points
and certain in vivo systemic efforts; e.g., thymic atrophy and body weight
loss.
The above criteria were applied as described below.
1. Since the primary concern is with chronic effects, the relative
carcinogenicity response (Table 2) for 2,3,7,8-TCDD and the mixture
of two 2378-HxCDDs4 were used to generate the TEF for 2378-PeCDD.
The TEFfor2378-PeCDD (0.5) is the arithmetic mean of the carcinogenic
potency values for 2,3,7,8-TCDD (1) and 2378-HxCDDs (0.04). Data
on receptor binding, enzyme induction, and cell keratinization generally
support this values.
2. 2,3,7,8-TCDF is assigned a TEF of 0.1 primarily because it is 1 to 2
orders of magnitude (OMs).less potent than 2,3,7,8-TCDD in
reproductive toxicity tests. Also, it is about one OM less potent than
2,3,7,8-TCDD in the in vitro tests.
3. The 2378-PeCDF congeners are assigned a TEF of 0.1 due to the
responses seen in in vitro tests. Greater reliance was placed on the
animal enzyme induction studies due to the more significant
correlations observed between this end point and subchronic responses
than have been observed with the receptor binding end point. The
human cell data were accorded less weight because these experiments
were conducted at only one exposure concentration.
4. Because in vitro data in general show HxCDFs to be about one tenth
as potent as PeCDFs, their TEF is assigned a value of 0.01 (0.1/10).
Further, the data generally suggest that CDFs are somewhat less toxic
than the analogous CDDs. Therefore, the TEF for 2378-HxCDFs should
be less than that of the 2378-HxCDDs (0.04).
5. The 2378-HpCDDs and 2378-HpCDFs are assigned TEFs 3 OM less
than that for 2,3,7,8-TCDD because the enzyme induction potencies
of these congeners differ from that of 2,3,7,8-TCDD by about this factor.
"See Appendix A, item 6, for explanation of notation.
11
-------
6. Based on the data in Table 2, the non-2378-substituted isomers are
1 to 2 OMs less potent than the 2378-substituted isomers. Since these
data are limited to in vitro systems, a factor of 0.01 is applied to the
non-2378-substituted, as compared to the 2378-substituted congeners.
With the exception of 2,3,7,8-TCDD, the 2378-HxCDDs, and 2378-TCDF,
the TEFs are not based on the results of major animal (reproductive,
carcinogenic) studies. Generally, TEFs are based on estimates of the relative
toxicity in in vitro tests whose relationship to the chronic effects of concern
is largely presumptive. However, as discussed above, studies on systemic
effects continue to reinforce the view that the short-term assays provide
important fundamental information on the toxicity of the CDDs and CDFs.
In summary, the Forum concludes that there is a sufficiently plausible
basis for the TEF approach of estimating risks associated with exposures
to CDDs and CDFs and recommends that the Agency adopt the approach,
on an interim basis, as a matter of science policy. The TEFs should be revised
as additional scientific information is developed. It should be noted that this
general approach to estimating such CDD/CDF risks has been taken by other
regulatory groups (see Table 1 and Appendix B).
12
-------
V. Applications to Risk Assessment
In general, as assessment of the human health risk of a mixture of CDDs
and CDFs, using the TEF approach, involves the following steps:
1. Analytical determination of the CDDs and CDFs in the sample.
2. Multiplication of congener concentrations in the sample by the TEFs
in Table 1 to express the concentration in terms of 2378-TCDD
equivalents.
3. Summation of the products in step 2 to obtain the total 2378-TCDD
equivalents in the sample.
4. Determination of human exposure to the mixture in question, expressed
in terms of 2378-TCDD equivalents.
5. Combination of exposure from step 4 with toxicity information on
2,3,7,8-TCDD (usually carcinogenicity and/or reproductive effects) to
estimate risks associated with the mixture.
In cases in which the concentrations of the 15 congeners are known:
2378-TCDD Equivalents = I (TEF of each 2378-CDD/CDF congener
X the concentration of the respective congener)
+ I (TEF of each non-2378-CDD/CDF congener
X the concentration of the respective congener)
Samples of this calculation for several environmental mixtures are provided
in Table 4.
In cases where only the concentration of homologous groups is known,
i.e., no isomer-specific data are available, different approaches are possible.
For example, the assumption that the 2378-congeners of concern constitute
all of the CDDs and CDFs present in the mixture is likely to provide an upper-
bound, most conservative estimate of the toxicity. Alternatively, one could
assume that the occurrence of each of the congeners in the mixture has
equal probability (Olie et al., 1983; Commoner et al., 1984). For instance
2,3,7,8-TCDD is one of 22 possible TCDDs and would constitute about 4%
of a mixture of isomers occurring with equal probability. In other situations
particular knowledge of chemical reaction parameters, process conditions,
and results from related studies (e.g., congener distributions in emissions
form combustion sources) might enable one to estimate the relative
occurrence of 2378-congeners. However, one must be careful to explicitly
explain and justify whatever assumptions are made. Table 5 illustrates the
results obtained using different methods to estimate the proportion of 2378
to non-2378 isomers in the absence of analytical data for individual isomers.
The calculated 2378-TCDD equivalents can then be used to assess the
health risk of a mixture. As an explicit example, consider a municipal solid
waste (MSW) combustor whose particulate emissions, the CDD/CDF mixture
in question, are the same as the electrostatic precipitator (ESP) catch cited
in columns 5 and 6 of Table 4. The sample is estimated to contain 32 ppb
2378-TCDD equivalents; i.e., 32 picograms of 2378-TCDD equivalents per
milligram of mixture. Suppose that an exposure analysis indicates that a
person living downwind from the incinerator receives an average daily dose
of 1 ng of the mixture/kg body weight resulting from inhalation (i.e., without
consideration of other possible routes of exposure). This exposure estimate
is combined with the upper-bound carcinogenic potency of 2,3,7,8-TCDD
(1.6 X 105 per mg/kg-day [U.S. EPA, 1984b]) to generate the upper 95%
13
-------
Table 4. PCDDs/PCDFs in Some Environmental Samples
Air parties.
St. Louis8
Isomer TEF
CDD/F
cone.
TCDD
eqts.
MSW
ESP dust*
CDD/F TCDD
cone. eqts.
(ppb)
TCDDs 1
PeCDDs 0.5
HxCDDs 0.04
HpCDDs 0.001
OCDD 0
TCDFs 0.1
PeCDFs 0.1
HxCDFs 0.01
HpCDFs 0.001
OCDF 0
0.2
1
1.2
25
170
—
—
—
—
—
0.2
0.5
0.048
0.025
0
—
—
—
—
—
5
10
160
120
260
40
80
280
160
40
(ppb)
5
5
6.4
0.12
0
4
8
2.8
0.16
0
Lake
sediment8
CDD/F
cone.
TCDD
eqts.
(ppb)
0
0.1
0.34
0.5
1.3
0.13
0.14
0.38
1.13
0.14
0
0.05
0.014
0.001
0
0.013
0.014
0.004
0.001
0
1982
Milorganited
CDD/F TCDD
cone. eqts.
(ppt)
206 206
— —
2768 770.7
7600 7.6
60000 0
— —
— —
— —
— —
— —
MSW fly ash f
Ontario Oslo
CDD/F TCDD
cone.
541
467
591
434
467
—
—
—
—
—
eqts.
(ppt)
541
234
24
0.43
0
—
—
—
—
CDD/F TCDD
cone.
(ppt)
ND
11
51
119
186
eqts.
__
5.5
2
0.12
0
—
—
Total TCDD eqts.
0.08
32
0.10
324
799
7.3
-------
Table 4. (continued)
Thermal degradation prods.
from dielectric fluids'
Run
8-13-40
Isomer
TEF
CDD/F
cone.
TCDD
eqts.
Japanese MSV\/°
Commercial CPs
Soot from
PCB fires
Run
8-30-61 ASKL
CDD/F
cone.
TCDD
eqts.
Pt.
A TEF
CDD/F TCDD
cone.
(ng) (\i,g)
TCDDs
2378
other
PeCDDs
2378
other
HxCDDs
2378
other
HpCDDs
2378
other
OCDD
1
0.01
0.5
0.002
0.04
0.0004
0.001
0.00001
0
0
0
0
0
0
0
0
0
0
0
0
0
0
330
37
0
0
0
0.33
0
0.1
0.07
0.04
0.02
0.01
eqts.
Pt.BTEF
CDD/F
cone.
TCDD
eqts.
[lb/MMBTU(x10-6)]
0.1
0.035
0.002
<0.001
0
0.58
0.47
0.36
0.08
0.04
0.58
0.24
0.014
<0.001
0
246TCPC PCPC
CDD/F TCDD CDD/F TCDD
cone. eqts. cone. eqts.
(ppm) (ppm)
<0. 1 — <0. 1 —
<0. 1 — <0. 1 —
<1 — 2.5 0.1
<1 — 175 0.18
<1 0 500 0
CDD/F TCDD
cone. eqts.
(ppm)
0.6 0.6
0.6 0.01
2.5 1.25
2.5 0.01
1.1 0.04
3.6
3
4
2 0
-------
Table 4. (continued)
Thermal degradation prods.
from dielectric fluids'
Isomer
TCDFs
2378
other
PeCDFs
2378
other
HxCDFs
2378
other
HpCDFs
2378
other
OCDF
TEF
0.1
0.001
0.1
0.001
0.01
0.0001
0.001
0.00001
0
Total TCDD eqts.
Run
8-13-40
CDD/F TCDD
cone. eqts.
(ng)
690 69
43 4.3
7 0.07
0 0
0 0
73
Run
8-30-61 ASKL
CDD/F TCDD
cone. eqts.
(»9)
1400 140
6400 640
910 9. 1
29 0.029
3.4 0
789
Japanese MSWb
Pt. A TEF
Pt. B TEF
CDD/F TCDD CDD/F TCDD
cone. eqts. cone. eqts.
[Ib/MMBTUdO'6)]
1.31 0. 131
0.38 0.038
0.06 0.006
0.01 <.001
0.004 0
0.3
1.25 0. 125
0.46 0.046
0.06 0.006
0.02 <.001
0.01 0
1.02
Commercial CPs
246TCPC PCPC
CDD/F TCDD CDD/F TCDD
cone. eqts. cone. eqts.
(ppm) (ppm)
1.5 0.15 <0.1
17.5 1.75 <0.1
36 3.6 <0.3
4.8 0.005 19 0.019
<1 0 25 0
5.5 0.3
Soot
PCB
from
fire"
CDD/F TCDD
cone. eqts.
(ppm)
12
16
358
312
670
295
285
172
40
1.2
0.01
35.8
0.3
6.7
0.03
0.29
0
0
46
aU,S. EPA. 1984c.
bCooper Engineers, 1984.
cRappe, 1984
dLamparski et a/., 7984.
"Czuwa and Hites, 1984.
fTong et a/., 1984.
BDes Hosiers, 1984.
-------
Table S. Use of the TEF Approach
PCS fire soot3
MSW fly
Sample 1
Isomer
Total TCDDs
2378 TCDDs
other TCDDs
Total PeCDDs
2378 PeCDDs
other PeCDDs
Total HxCDDs
2378 HxCDDs
other HxCDDs
Total HpCDDs
2378 HpCDDs
other HpCDDs
Total TCDFs
2378 TCDFs
other TCDFs
TEF
1
1
0.01
0.5
0.5
0.005
0.04
0.04
0.0004
0.001
0.001
0.00001
0.1
0.1
0.001
Propn.
factor
1
0.05
0.95
1
0.07
0.93
1
0.3
0.7
1
0.5
0.5
1
0.03
0.97
CDD/F
cone.
(ppm) Ac
1.2 1.2
1.2
1.2
5.0 2.5
5.0
5.0
4.7 0.2
4.7
4.7
7
7
7
28 2.8
28
28
TCDD eqts.
(ppm)
B° Cc
0.2 0.6
d
0.2 1.3
—
0.1
— —
__
—
—
0.1 1.2
—
CDD/F
Dc (ppb)
85
85
85
213
213
213
354
354
354
184
184
184
209
209
209
TCDD eqts.
Ac Bc l
85
4.3
0.8
107
7.0
1.0
14.2
4.3
0.1
0.2
0.1
—
20.9
0.6
0.2
ash"
Sample 2
CDD/F
cone
Oc (ppb)
2.7
2.7
2.7
6.6
6.6
6.6
11.6
11.6
11.6
5.7
5.7
5.7
7.0
7.0
7.0
TCDD
eqts.
(ppb)
Ac Bc Dc
2.7
0.1
3.3
0.2
0.5
0.1
__._
—
0.7
—
-------
Table 5. (continued)
PCB fire soot3
Isomer TEF
Total PeCDFs 0. 1
2378 PeCDFs 0. 1
other PeCDFs 0.001
Total HxCDFs 0.01
2378 HxCDFs 0.01
other HxCDFs 0.0001
Total HpCDFs 0.001
2378 HpCDFs 0.001
other HpCDFs 0.00001
Propn.
factor
1
0.07
0.93
1
0.25
0.75
1
0.50
0.50
Total estimated TCDD equivalents ITEF)
Measured TCDD Equivalents
AHH bioassay
EFtOD bioassay
Receptor binding assay
CDD/F
cone
(ppm) Ac
670 67
670
670
965 9.7
965
965
460 0.5
460
460
84
TCDD eqts.
(ppm)
Bc Cc
4.7 35.8
0.6 0.3
2.4 6.7
0.1
0.2 0.3
8 46
CDD/F
Dc (ppb)
549
549
549
1082
1082
1082
499
499
499
—
MSW fly ashb
Sample 1
TCDD eqts.
(ppb)
Ac Bc Dc
54.9
3.8
0.5
10.8
2.7
0.1
0.5
0.2
294 26
4
5
32
Sample 2
TCDD
cone
(ppb) Ac Bc Dc
17.8 1.8
17.8 0. 1
17.8
32.1 0.3
32.1 0.1
32.1
10.9
10.9
10.9
9 1
4
Acute toxicity bioassay
58
-------
Table S. (continued)
MSW fly ashb
Isomer
Total TCDDs
2378 TCDDs
other TCDDs
Total PeCDDs
2378 PeCDDs
other PeCDDs
Total HxCDDs
2378 HxCDDs
other HxCDDs
Total HpCDDs
2378 HpCDDs
other HpCDDs
Total TCDFs
2378 TCDFs
other TCDFs
Total PeCDFs
2378 PeCDFs
other PeCDFs
TEF
1
1
0.01
0.5
0.5
0.005
0.04
0.04
0.0004
0.001
0.001
0.00001
0.1
0.1
0.001
0.1
0.1
0.001
Propn.
factor
1
0.05
0.95
1
0.07
0.93
1
0.3
0.7
1
0.5
0.5
1
0.03
0.97
1
0.07
0.93
CDD/F
cone.
(ppb)
12.9
12.9
12.9
37.5
37.5
37.5
75
75
75
41.9
41.9
41.9
8.2
8.2
8.2
19.8
19.8
19.8
Sample 3
TCDD eqts.
(ppb)
Ac Bc
12.9
0.6
0.1
18.8
1.3
0.2
3
0.9
—
—
—
—
0.8
—
—
2.0
0.1
—
CDD/F
cone
Dc (ppb)
2.4
2.4
2.4
7.9
7.9
7.9
9.7
9.7
9.7
9.1
9.1
9.1
4.4
4.4
4.4
21.0
21.0
21.0
Sample 4
TCDD eqts.
(ppb)
A° Bc Dc
2.4
0.1
—
4.0
0.3
—
0.4
0.1
—
—
—
—
0.4
—
—
2.1
0.1
—
-------
Table S. (continued)
to
o
MSW fly ash"
Isomer TEF
Total HxCDFs 0.01
2378 HxCDFs 0.01
other HxCDFs 0.0001
Total HpCDFs 0.001
2378 HpCDFs 0.001
other HpCDFs 0.00001
Total estimated TCDD equivalents (TEF)
Measured TCDD Equivalents
AHH bioassay
EROD bioassay
Receptor binding assay
Acute toxicity bioassay
Propn.
factor
1
0.25
0.75
1
0.50
0.50
Sample 3
TCDD eqts.
CDD/F (ppb)
cone
(ppb) Ac Bc Dc
38.7 0.4
38.7 0.1
38.7
20.6
20.6
20.6
38 2
4
5
65
— "~
CDD/F
cone.
(ppb)
21.6
21.6
21.6
16.6
16.6
16.6
Sample 4
TCDD eqts.
(ppb)
Ac Bc Dc
0.2
0.1
—
—
—
~~—
9 0.7
2
2
11
aDes Hosiers, 1984, assuming only homologue-specific concentrations are known (for isomer-specific analyses; see Table 4).
bSawyer et a/., 7983.
CA = estimated assuming 2378-isomers constitute 100% of a homologous group.
B = estimated assuming occurrence of all isomers in a homologous group is equally probable (thus using the proportionality factor
in column three).
C = estimated by utilizing isomer-specific analyses (see Table 4).
D = estimated by direct bioassay.
^Values rounding off to less than 0.1 are omitted.
-------
limit of the excess risk of developing cancer (from inhalation exposure alone)
for a person living downwind from the facility emitting the mixture under
consideration, assuming lifetime exposure:
upper 95% limit of excess cancer risk resulting from inhalation exposure
= [potency] x [exposure]
= [1.6 x 105 per mg 2,3,7,8-TCDD/kg-day]
x [32 pg TCDD/mg mixture x 10"9 mg 2,3,7,8-TCDD/pg
x 1 ng mixture/kg-day x 10~6 mg mixture/ng mixture].
21
-------
VI. Comparison of the TEF Approach with
Results of Biological Testing
A limited number of in vivo and in vitro approaches have been employed
in assessing the toxicity of complex mixtures of CDDs and CDFs. While the
results from these attempts are not definitive, it is instructive to compare
those results with the results from the TEF approach proposed here.
Eadon et al. (1982) investigated the toxicity of CDD/CDF-contaminated
soot associated with a fire involving PCB-containing electrical equipment.
Using the results from acute in vivo toxicity (LD50) studies in which the soot
was the test substance, the researchers determined that it had the acute
toxicity expected of material containing about 60 times the amount of 2,3,7,8-
TCDD actually found by GC/MS analysis.
Table 5 illustrates the results of employing the TEF approach through three
different procedures, each of which depends upon the results of GC/MS
analysis of the soot. In the first instance (A, in Table 5), the analytical data
have been consolidated to totals within a homologous class. These
concentrations are treated as if they consisted completely of 2378-members
of the class and, therefore, are multiplied by the TEF appropriate for the
2378-members of the class. The resulting estimate of 2378-TCDD equivalents
by this procedure is about 80.
In procedure B the assumption is made that the occurrence of each of
the congeners in a homologous class is equally probable; e.g., the
concentration of 2,3,7,8-TCDD is 1 /22 (about 5%) of the concentration of
the total TCDDs. This approach leads to an estimate of the total 2378-TCDD
equivalents of 8.
A rather unique data base exists in the case of the soot from this fire
in that an extensive isomer-specific analysis of the sample is available (as
cited in Des Rosiers, 1984). Therefore, the full array of TEFs from Table
1 (using the current EPA recommendations) can be applied. This procedure
(C in Table 5) results in an estimate of roughly 50 for the total 2378-TCDD
equivalents in the sample.
As might be expected, the most conservative of these procedures. A, leads
to the highest estimate. Approach B (using theoretical probability of
occurrence) leads to an estimate that is about 10-fold lower than the isomer-
specific results C, relfecting the fact that the 2378-congeners are present
in somewhat higher than "equal probability" proportions in this particular
soot sample. Given the complexity of the analysis involved, the approximate
nature of the TEF method, and the vagaries of the assay, a major feature
of note in Table 5 regarding the soot samples is that the results of procedures
A, B, and C span a range of only one order of magnitude and bracket the
bioassay estimate, reported by Eadon et al. (1982).
Table 5 also shows the results of the application of approaches A and
B to published results of homologue-specific CDD and CDF concentrations
in fly ash from four municipal solid waste combustors (Sawyer et al., 1983).
In addition, extracts from the fly ash samples were analyzed by three bioassay
techniques (AHH induction, EROD induction, and receptor binding). Again,
the calculated results span an order of magnitude, with the bioassay results
lying within or close to this range.
These data suggest that the TEF approach is likely to be a useful interim
tool for the rough (order of magnitude) estimation of the toxicity of complex
mixtures of CDDs and CDFs. The availability of additional data comparing
22
-------
the results of analytical and biological assays will enable a conclusion
regarding the preferred method of estimating TEFs (e.g., method A or B of
Table 5).
23
-------
VII. Research Needs
The Forum recommends that the Agency support research that would allow
actual measurement of mixtures containing CDDs and CDFs, rather than
drawing inferences from component toxicity. The results of this research
could reduce the need for the TEF approach. In addition, research should
be conducted in order to provide a firmer basis for, and to guide appropriate
modification of, the TEF approach. Several areas of research are appropriate
for these purposes.
1. Validation and completion of the in vitro test data such as those listed
in Table 2.
2. Investigation of the relationships between short-term//? vivo and in vitro
tests and the toxic end points of concern; i.e., carcinogenicity,
reproductive toxicity, immunotoxicity, and other singificant human
health effects resulting from CDD/CDF exposure.
3. Determination of the impact of pharmacodynamics, including
bioavailability, potential for absorption, and toxic potencies of
metabolites of CDDs and CDFs in in vitro tests, relative to the potencies
of the parent compounds. As pointed out by several reviewers, this
would enable refinement of the TEF approach.
4. Investigation of additional short-term assays which can test the
mechanistic hypotheses underlying the TEF approach.
24
-------
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27
-------
Appendix A
Nomenclature
The following terminology and abbreviations are used in this document:
1. The term "congener" refers to any one particular member of the same
chemical family; e.g., there are 75 congeners of chlorinated dibenzo-
p-dioxins.
2. The term "homologue" refers to a group of structurally related
chemicals that have the same degree of chlorination. For example,
there are eight homologues of CDDs, monochlorinated through
octochlorinated.
3. The term "isomer" refers to substances that belong to the same
homologous class. For example, there are 22 isomers that constitute
the homologues of TCDDs.
4. A specific congener is denoted by unique chemical notation. For
example, 2,4,8,9-tetrachlorodibenzofuran is referred to as 2,4,8,9-
TCDF.
5. Notation for homologous classes is as follows:
Dibenzo-p-dioxin D
Dibenzofuran F
No. of halogens Acronym Example
1 M
2 D 2,4-DCDD
3 Tr
4 T 1,4,7,8-TCDD
5 Pe
6 Hx
7 Hp
8 O
1 through 8 CDDs and CDFs
6. Dibenzo-p-dioxins and dibenzofurans that are chlorinated at the 2,3,7,
and 8 positions are denoted as "2378" congeners, except when 2,3,7,8-
TCDD is uniquely referred to; e.g., 1,2,3,7,8-PeCDF and 2,3,4,7,8-PeCDF
are both referred to as "2378-PeCDFs."
A-1
-------
Appendix B
Comparison of Different Approaches to Calculating
2378-TCDD Equivalents
Table 1 in the text lists a number of different approaches for calculating
2378-TCDD toxicity equivalents. Five of the approaches (those that deal with
4-position 2378-substituted congeners, but not 3-position substituted
congeners) were applied to the data in Table 4 in the text.
These approaches were also applied to some of the data included in Table
I of the Report of the Citizens Advisory Committee on Resource Recovery
in Brooklyn (March, 1985), produced by Ketcham and the Mt. Sinai School
of Medicine.
A summary comparison of the relative results is found in Table B-1, with
the supporting tables (Tables B-2 through B-13) attached. (Note that the
units of mass emission are not the same for all of the facilities. Therefore,
comparison of absolute numbers between facilities may be invalid).
These data indicate that, in general, the methods used by the Swiss
government. New York State, and the U.S. EPA (the 1981 approach and
the 1985 proposal) all generate results which are within an order of magnitude
of each other. This suggests that, within the range considered, the results
are not particularly sensitive functions of the TEFs selected.
The procedure recommended by the state of California, however, gives
results which are roughly an order of magnitude higher than those generated
by the other approaches. In general, the greater the contribution from the
TCDDs, the greater the similarity in the results of the methods. This is due
to the fact that all methods assign a TEF of 1 for 2,3,7,8-TCDD (and 1 to
all TCDDs, when isomer-specific analyses are not available). Because higher
chlorinated CDDs and CDFs contribute significantly to the total, the disparity
is greater between the state of California results and those produced by
the other methods, since California assumes that all 2378-substituted CDDs
and CDFs are as potent as 2,3,7,8-TCDD. The other methods acknowledge,
to one degree or another, the reduced toxicity of higher chlorinated species;
see Table 2.
B-1
-------
Table 0-7. Relative 2378-TCDD Equivalents*
Source
St. Louis
air particulates
PCB fire soot
(isomer-specific)
MSW ESP dust
Lake sediment
Milorganite
Oslo MSW flyash
Ontario MSW flyash
Japanese plant A
Japanese plant B
Albany
Wright-Patterson (best)
Wright-Patterson (worst)
EPA '85
1
1
1
1
1
1
1
1
1
1
1
1
EPA '81
0.3
0.03
0.2
—
0.6
—
0.8
0.3
0.6
0.3
0.2
0.4
Swiss
1
4
3
2
2
1
1
1
0.8
0.4
2
2
NY
2
3
2
2
0.9
2
2
2
2
2
3
2
CA
40
30
30
30
30
20
3
7
3
5
20
20
"Calculated using the Toxicity Equivalence Factors shown in Table 1.
B-2
-------
Table B-2. Calculation of 2378-TCDD Toxicity Equivalents for St. Louis Air Particulates Using Homologue-Specific Data
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
CD HxCDDs
CO
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
CDD/F
cone.
(ppb)
X
0.2
0
1
0
1.2
0
25
0
170
X
NA
0
NA
0
NA
0
EPA 1985
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
TEs
(ppb)
0
0.2
0
0.5
0
0.048
0
0.025
0
0
0
0
0
0
0
0
0
EPA
TEFs
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1981
TEs
(ppb)
0
0.2
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
TEs
(ppb)
0
0.2
0
0.1
0
0.12
0
0.25
0
0
0
0
0
0
0
0
0
New
TEFs
0
1
0
1
0
0.03
0
0
0
0
0
0.33
0
0.33
0
0.01
0
York
TEs
(ppb)
0
0.2
0
1
0
0.036
0
0
0
0
0
0
0
0
0
0
0
California
TEFs
0
1
0
1
0
1
0
1
0
0
0
1
0
1
0
1
0
TEs
(ppb)
0
0.2
0
1
0
1.2
0
25
0
0
0
0
0
0
0
0
0
-------
Table B-2. (continued)
Compound
2378-HpCDF
HpCDFs
OCDF
CDD/F
cone.
(ppb)
NA
0
NA
. EPA 1985
TEFs
0.001
0.00001
0
Total 2378-TCDD equivalents
CO
Table B-3.
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
Calculation of 2378-TCDD
CDD/F
cone.
(ppm)
X
0.6
0.6
2.5
2.5
TEs
(ppb)
0
0
0
0.7
Toxicity
EPA 1985
TEFs
0
1
0.01
0.5
0.005
TEs
(ppm)
0
0.6
0.006
1.25
0.0125
EPA 1981
TEFs
0
0
0
Equivalents
TEs
(ppb)
0
0
0
0.2
for PCB
EPA 1981
TEFs
0
1
1
0
0
TEs
(ppm)
0
0.6
0.6
0
0
Switzerland
TEFs
0.1
0
0
Fire Soot
TEs
(ppb)
0
0
0
0.7
New York
TEFs
0
0
0
Using Isomer-Specific
Switzerland
TEFs
0
1
0.01
0.1
0.1
TEs
(ppm)
0
0.6
0.006
0.25
0.25
TEs
(ppb)
0
0
0
1.2
Data
New York
TEFs
0
1
0
1
0
TEs
(ppm)
0
0.6
0
2.5
0
California
TEFs
1
0
0
TEs
(ppb)
0
0
0
27.4
California
TEFs
0
1
0
1
0
TEs
(ppm)
0
0.6
0
2.5
0
-------
Table B-3.
(continued)
Compound
2378-HxCDD
HxCDDs
2378-HpCDD
HpCDDs
OCDD
Mono to tri
w
01 2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
2378-HpCDF
HpCDFs
OCDF
Total 2378-TCDD
CDD/F
cone.
(ppm)
1,1
3.6
3
4
2
X
12
16
358
312
670
295
285
172
40
equivalents
EPA
TEFs
0.04
0.0004
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
0.001
0.00001
0
1985
TEs
(ppm)
0.044
0.00144
0.003
0.00004
0
0
1.2
0.016
35.8
0.312
6.7
0.0295
0.285
0.00172
0
46
EPA
TEFs
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1981
TEs
(ppm)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1.2
Switzerland
TEFs
0.1
0.1
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
0
TEs
(ppm)
0.11
0.36
0.03
0.04
0
0
1.2
1.6
35.8
31.2
67
29.5
28.5
0
0
196
New York
TEFs
0.03
0
0
0
0
0
0.33
0
0.33
0
0.01
0
0
0
0
TEs
(ppm)
0.033
0
0
0
0
0
3.96
0
118.14
0
6.7
0
0
0
0
132
California
TEFs
1
0
1
0
0
0
1
0
1
0
1
0
1
0
0
TEs
(ppm)
1.1
0
3
0
0
0
12
0
358
0
670
0
285
0
0
1332
-------
Table B-4. Calculation of 2378-TCDD Toxicity Equivalents for MSW ESP Dust Using Homologue-Spec'rfic Data and 2378 TEFs
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
co HxCDDs
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
CDD/F
cone.
(ppb)
X
5
0
10
0
160
0
120
0
260
X
40
0
80
0
280
0
EPA 1985
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
0.001
0.00001
0
0
0.1
.001
0.1
0.001
0.01
0.0001
TEs
(ppb)
0
5
0
5
0
6.4
0
0.12
0
0
0
4
0
8
0
2.8
0
EPA
TEFs
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1981
TEs
(ppb)
0
5
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
TEs
(ppb)
0
5
0
1
0
16
0
1.2
0
0
0
4
0
8
0
28
0
New York
TEFs
0
1
0
1
0
0.03
0
0
0
0
0
0.33
0
0.33
0
0.01
0
TEs
(ppb)
0
5
0
10
0
4.8
0
0
0
0
0
13.2
0
26.4
0
2.8
0
California
TEFs
0
1
0
1
0
1
0
1
0
0
0
1
0
1
0
1
0
TEs
(ppb)
0
5
0
10
0
160
0
120
0
0
0
40
0
80
0
280
0
-------
Table B-4. (continued)
Compound
2378-HpCDF
HpCDFs
OCDF
CDD/F
cone.
(ppb)
160
0
40
EPA
TEFs
0.001
0.00001
0
Total 2378-TCDD equivalents
CD Table B-5.
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
HxCDDs
Calculation
CDD/F
cone.
(ppb)
X
0
0
0.1
0
0.34
0
1985
TEs
(ppb)
0.16
0
0
31
EPA 1981
TEFs
0
0
0
of 2378-TCDD Toxicity Equivalents
EPA
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
1985
TEs
(ppb)
0
0
0
0.05
0
0.0136
0
TEs
(ppb)
0
0
0
5
for Lake
EPA 1981
TEFs
0
1
1
0
0
0
0
TEs
(ppb)
0
0
0
0
0
0
0
Switzerland
TEFs
0.1
0
0
Sediment
TEs
(ppb)
16
0
0
79
New York
TEFs
0
0
0
TEs
(ppb)
0
0
0
62
California
TEFs
1
0
0
TEs
(ppb)
160
0
0
855
Using Homologue-Specific Data
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
TEs
(ppb)
0
0
0
0.01
0
0.034
0
New
TEFs
0
1
0
1
0
0.03
0
York
TEs
(ppb)
0
0
0
0.1
0
0.0102
0
California
TEFs
0
1
0
1
0
1
0
TEs
(ppb)
0
0
0
0.1
0
0.34
0
-------
Table B-5. (continued)
Compound
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
CD
* 2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
2378-HpCDF
HpCDFs
OCDF
Total 2378-TCDD
CDD/F
cone.
(ppb)
0.5
0
1.3
X
0.13
0
0.14
0
0.38
0
1.13
0
0.14
equivalents
EPA 1985
TEFs
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
0.001
0.00001
0
TEs
(ppb)
0.0005
0
0
0
0.013
0
0.014
0
0.0038
0
0.00113
0
0
0.1
EPA
TEFs
0
0
0
0
0
0
0
0
0
0
0
0
0
1981
TEs
(ppb)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Switzerland
TEFs
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
0
TEs
(ppb)
0.005
0
0
0
0.013
0
0.014
0
0.038
0
0.113
0
0
1.2
New York
TEFs
0
0
0
0
0.33
0
0.33
0
0.01
0
0
0
0
TEs
(ppb)
0
0
0
0
0.0429
0
0.0462
0
0.0038
0
0
0
0
0.2
California
TEFs
1
0
0
0
1
0
1
0
1
0
1
0
0
TEs
(ppb)
0.5
0
0
0
0.13
0
0.14
0
0.38
0
1.13
0
0
2.7
-------
Table B-6. Calculation of 2378-TCDD Toxicity Equivalents for Milorganite Using Homologue-Spec'rfic Data
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
co HxCDDs
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
CDD/F
cone.
(ppt)
X
206
0
0
0
2768
0
7600
0
60000
X
NA
0
NA
0
NA
0
EPA
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
1985
TEs
(Ppt)
0
206
0
0
0
110.72
0
7.6
0
0
0
0
0
0
0
0
0
EPA 1981
TEFs
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
TEs
(ppt)
0
206
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
TEs
(ppt)
0
206
0
0
0
276.8
0
76
0
0
0
0
0
0
0
0
0
New York
TEFs
0
1
0
1
0
0.03
0
0
0
0
0
0.33
0
0.33
0
0.01
0
TEs
(ppt)
0
206
0
0
0
83.04
0
0
0
0
0
0
0
0
0
0
0
California
TEFs
0
1
0
1
0
1
0
1
0
0
0
1
0
1
0
1
0
TEs
(Ppt)
0
206
0
0
0
2768
0
7600
0
0
0
0
0
0
0
0
0
-------
Table B-6. (continued)
Compound
2378-HpCDF
HpCDFs
OCDF
Total 2378-TCDD
CDD/F
cone.
NA
0
NA
equivalents
EPA
TEFs
0.001
0.00001
0
1985
TEs
0
0
0
324
09
£ Table B-7. Calculation of 2378-TCDD Toxicity
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
HxCDDs
CDD/F
cone.
(ppt)
X
NA
0
11
0
51
0
EPA
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
1985
TEs
(ppt)
0
0
0
5.5
0
2.04
0
EPA 1981
TEFs
0
0
0
Equivalents
TEs
(ppt)
0
0
0
206
for Oslo
EPA 1981
TEFs
0
1
1
0
0
0
0
TEs
(ppt)
0
0
0
0
0
0
0
Switzerland
TEFs
0.1
0
0
TEs
(ppt)
0
0
0
559
MSW Fly Ash Using
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
TEs
(ppt)
0
0
0
1.1
0
5.1
0
New York
TEFs
0
0
0
TEs
(ppt)
0
0
0
289
California
TEFs
1
0
0
TEs
(ppt)
0
0
0
10600
Homologue-Specific Data
New
TEFs
0
1
0
1
0
0.03
0
York
TEs
(ppt)
0
0
0
11
0
1.53
0
California
TEFs
0
1
0
1
0
1
0
TEs
(ppt)
0
0
0
11
0
51
0
-------
Table B-7.
(continued)
CDD/F
Compound cone.
(ppt)
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
2378-HpCDF
HpCDFs
OCDF
Total 2378-TCDD
119
0
186
X
NA
0
NA
0
NA
0
NA
0
NA
equivalents
EPA 1985
TEFs
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
0.001
0.00001
0
TEs
(ppt)
0.119
0
0
0
0
0
0
0
0
0
0
0
0
7.7
EPA
TEFs
0
0
0
0
0
0
0
0
0
0
0
0
0
1981
TEs
(ppt)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Switzerland
TEFs
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
0
TEs
(ppt)
1.19
0
0
0
0
0
0
0
0
0
0
0
0
7.4
New
TEFs
0
0
0
0
0.33
0
0.33
0
0.01
0
0
0
0
York
TEs
(ppt)
0
0
0
0
0
0
0
0
0
0
0
0
0
12.5
California
TEFs
1
0
0
0
1
0
1
0
1
0
1
0
0
TEs
(PPt)
119
0
0
0
0
0
0
0
0
0
0
0
0
181
-------
Table B-8. Calculation of 2378-TCDD Toxicity Equivalents for Ontario MSW Fly Ash Using Homologue-Specific Data
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
-------
Table B-8.
(continued)
Compound
2378-HpCDF
HpCDFs
OCDF
CDD/F
cone.
(PPt)
NA
0
NA
EPA
TEFs
0.001
0.00001
0
Total 2378-TCDD equivalents
Table 8-9.
Compound
'Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
HxCDDs
Calculation
CDD/F
conc.a
X
0.1
0
0.07
0
0.04
0
1985
TEs
(PPt)
0
0
0
799
of 2378-TCDD Toxicity
EPA
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
1985
TEs"
0
0.1
0
0.035
0
0.0016
0
EPA 1981
TEFs
0
0
0
Equivalents
TEs
(PPt)
0
0
0
541
Switzerland
TEFs
0.1
0
0
TEs
(PPt)
0
0
0
651
for MSW at Japanese Plant A
EPA 1981
TEFs
0
1
1
0
0
0
0
TEsa
0
0.1
0
0
0
0
0
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
TEs"
0
0.1
0
0.007
0
0.004
0
New York
TEFs
0
0
0
Using
TEs
(PPt)
0
0
0
1026
California
TEFs
1
0
0
Homologue-Specific
New York
TEFs
0
1
0
1
0
0.03
0
TEs"
0
0.1
0
0.07
0
0.0012
0
TEs
(PPt)
0
0
0
2033
Data
California
TEFs
0
1
0
1
0
1
0
TEs"
0
0.1
0
0.07
0
0.04
0
-------
Table B-9. (continued)
Compound
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
2378-HpCDF
HpCDFs
OCDF
Total 2378-TCDD
CDD/F
cone. a
0.02
0
0.01
X
1.31
0
0.38
0
0.06
0
0.01
0
0.004
equivalents
EPA 1985
TEFs
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
0.001
0.00001
0
TEsa
0.00002
0
0
0
0.131
0
0.038
0
0,0006
0
0.00001
0
0
0.3
EPA
TEFs
0
0
0
0
0
0
0
0
0
0
0
0
0
1981
TEsa
0
0
0
0
0
0
0
0
0
0
0
0
0
0.1
Switzerland
TEFs
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
0
TEsa
0.0002
0
0
0
0.131
0
0.038
0
0.006
0
0.001
0
0
0.3
New
TEFs
0
0
0
0
0.33
0
0.33
0
0.01
0
0
0
0
York
TEsa
0
0
0
0
0.4323
0
0.1254
0
0.0006
0
0
0
0
0.7
California
TEFs
1
0
0
0
1
0
1
0
1
0
1
0
0
TEsa
0.02
0
0
0
1.31
0
0.38
0
0.06
0
0.01
0
0
2.0
aUnits = Ib/MM BTU(x 10~6)
-------
Table 8-70. Calculation of 2378-TCDD Toxicity Equivalents for MSW at Japanese Plant B Using Homologue-Specific Data
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
HxCDDs
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
CDD/F
cone.3
X
0.58
0
0.47
0
0.36
0
0.08
0
0.04
X
1.25
0
0.46
0
0.06
0
EPA 1985
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
TEs3
0
0.58
0
0.235
0
0.0144
0
0.00008
0
0
0
0.125
0
0.046
0
0.0006
0
EPA
TEFs
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1981
TEs3
0
0.58
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
TEs8
0
0.58
0
0.047
0
0.036
0
0.0008
0
0
0
0.125
0
0.046
0
0.006
0
New
TEFs
0
1
0
1
0
0.03
0
0
0
0
0
0.33
0
0.33
0
0.01
0
York
TEs8
0
0.58
0
0.47
0
0.0108
0
0
0
0
0
0.4125
0
0.1518
0
0.0006
0
California
TEFs
0
1
0
1
0
1
0
1
0
0
0
1
0
1
0
1
0
TEs8
0
0.58
0
0.47
0
0.36
0
0.08
0
0
0
1.25
0
0.46
0
0.06
0
-------
Table B-10. (continued)
Compound
2378-HpCDF
HpCDFs
OCDF
CDD/F
cone.3
0.02
0
0.01
EPA
TEFs
0.001
0.00001
0
Total 2378-TCDD equivalents
1985
TEsa
0.00002
0
0
1.0
EPA 1981
TEFs
0
0
0
TEsa
0
0
0
0.6
Switzerland
TEFs
0.1
0
0
TEsa
0.002
0
0
0.8
New York
TEFs
0
0
0
TEsa
0
0
0
1.6
California
TEFs
1
0
0
TEsa
0.02
0
0
3.3
'Units = Ib/MM BTUfx 10~6)
? Table B-11.
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
HxCDDs
Calculation
CDD/F
cone.
(ng/m3)
X
0.45
14
97
0
53
0
of 2378-TCDD Toxicity
EPA
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
1985
TEs
(ng/m3)
0
0.45
0.14
48.5
0
2.12
0
Equivalents for MSW at Albany Using
EPA
TEFs
0
1
1
0
0
0
0
1981
TEs
(ng/m3)
0
0.45
14
0
0
0
0
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
TEs
(ng/m3)
0
0.45
0.14
9.7
0
5.3
0
Homologue-Specific
New
TEFs
0
1
0
1
0
0.03
0
York
TEs
(ng/m3)
0
0.45
0
97
0
1.59
0
Data
California
TEFs
0
1
0
1
0
1
0
TEs
(ng/m3)
0
0.45
0
97
0
53
0
-------
Table 8-77. (continued)
CD
Compound
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
2378-HpCDF
HpCDFs
OCDF
CDD/F
cone.
(ng/m3)
71
0
10
X
2.1
33
21
0
4
0
1
0
2
EPA
TEFs
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
0.001
0.00001
0
Total 2378-TCDD equivalents
1985
TEs
(ng/m3)
0.071
0
0
0
0.21
0.033
2.1
0
0.04
0
0.001
0
0
54
EPA 1981
TEFs
0
0
0
0
0
0
0
0
0
0
0
0
0
TEs
(ng/m3)
0
0
0
0
0
0
0
0
0
0
0
0
0
14
Switzerland
TEFs
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
0
TEs
(ng/m3)
0.71
0
0
0
0.21
3.3
2.1
0
0.4
0
0.1
0
0
22
New York
TEFs
0
0
0
0
0.33
0
0.33
0
0.01
0
0
0
0
TEs
(ng/m3)
0
0
0
0
0.693
0
6.93
0
0.04
0
0
0
0
107
California
TEFs
1
0
0
0
1
0
1
0
1
0
1
0
0
TEs
(ng/m3)
71
0
0
0
2.1
0
21
0
4
0
1
0
0
250
-------
Table B-12. Calculation of 2378-TCDD Toxicity Equivalents for WP AFB (Best) Using Homologue-Specific Data
Compound
Mono to tri
2378-TCDD
TCDDs
2378-PeCDD
PeCDDs
2378-HxCDD
<» HxCDDs
CO
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
CDD/F
cone.
(ng/m3)
X
0.4
0
0.4
0
1
0
3
0
3
X
8
0
3
0
4
0
EPA
TEFs
0
1
0.01
0.5
0.005
0.04
0.0004
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
1985
TEs
(ng/m3)
0
0.4
0
0.2
0
0.04
0
0.003
0
0
0
0.8
0
0.3
0
0.04
0
EPA 1981
TEFs
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
TEs
(ng/m3)
0
0.4
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Switzerland
TEFs
0
1
0.01
0.1
0.1
0.1
0.1
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
TEs
(ng/m3)
0
0.4
0
0.04
0
0.1
0
0.03
0
0
0
0.8
0
0.3
0
0.4
0
New York
TEFs
0
1
0
1
0
0.03
0
0
0
0
0
0.33
0
0.33
0
0.01
0
TEs
(ng/m3)
0
0.4
0
0.4
0
0.03
0
0
0
0
0
2.64
0
0.99
0
0.04
0
California
TEFs
0
1
0
1
0
1
0
1
0
0
0
1
0
1
0
1
0
TEs
(ng/m3)
0
0.4
0
0.4
0
1
0
3
0
0
0
8
0
3
0
4
0
-------
Table B-12.
(continued)
Compound
2378-HpCDF
HpCDFs
OCDF
CDD/F
cone.
(ng/m3)
9
0
2
EPA
TEFs
0.001
0.00001
0
Total 2378-TCDD equivalents
-------
Table B-13. (continued)
Compound
2378-HpCDD
HpCDDs
OCDD
Mono to tri
2378-TCDF
TCDFs
CD
o 2378-PeCDF
PeCDFs
2378-HxCDF
HxCDFs
2378-HpCDF
HpCDFs
OCDF
CDD/F
cone.
(ng/m3)
32
0
16
X
31
0
15
0
23
0
93
0
8
EPA
TEFs
0.001
0.00001
0
0
0.1
0.001
0.1
0.001
0.01
0.0001
0.001
0.00001
0
Total 2378-TCDD equivalents
1985
TEs
(ng/m3)
0.032
0
0
0
3.1
0
1.5
0
0.23
0
0.093
0
0
11.0
EPA 1981
TEFs
0
0
0
0
0
0
0
0
0
0
0
0
0
TEs
(ng/m3)
0
0
0
0
0
0
0
0
0
0
0
0
0
4
Switzerland
TEFs
0.01
0.01
0
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
0
TEs
(ng/m3)
0.32
0
0
0
3.1
0
1.5
0
2.3
0
9.3
0
0
21.4
New York
TEFs
0
0
0
0
0.33
0
0.33
0
0.01
0
0
0
0
TEs
(ng/m3)
0
0
0
0
10.23
0
4.95
0
0.23
0
0
0
0
22.6 '•
California
TEFs
1
0
0
0
1
0
1
0
1
0
1
0
0
TEs
(ng/m3)
32
0
0
0
31
0
15
0
23
0
93
0
0
207
------- |