**DEPARTMENT OF THE ARMY**

**US ARMY ENVIRONMENTAL CENTER**

**5179 HOADLEY ROAD**

**ABERDEEN PROVING GROUND, MD 21010-5401**

October 29, 2003

Cleanup Division

Ms. Marilyn Brower

US Environmental Protection Agency

Risk Assessment Forum Staff NCEA

Office of Environmental Information Docket

Docket ID Number ORD-2003-0002

Mailcode: 28220T

1200 Pennsylvania Avenue, NW

Washington, DC 20460

Dear Ms. Brower:

The US Army Biological Technical Assistance Group (Army BTAG) as well as
other Army technical experts for the US Army Center for Health Promotion
and Preventive Medicine (USACHPPM) have reviewed the document "Framework
For Application of the Toxicity Equivalence Methodology For
Polychlorinated Dioxins, Furans and Biphenyls in Ecological Risk
Assessment (External Review Draft). USEPA 630/P-03/002A. 04 Jun 2003.
U.S. Environmental Protection Agency, Risk Assessment Forum, Washington,
DC, 94 pp. Docket Number: ORD-2003-0002."

The Army BTAG is a matrixed technical work group developed to provide
technical and scientific expertise for ecological risk assessments as
part of the Installation Restoration Program.

Our comments are provided as an enclosure. Some of our main points are
summarized below:

a\. The methods and the data to usefully quantify *non-carcinogenic*
risk from

tetra-chlorinated dioxin (TCDD), congeners, and other specific co-planar
polychlorinated biphenyls (PCBs) are lacking and the adverse effects
across vertebrate classes are too variable for use, presently. This
variation *cannot* be explained by affinity to the Ah receptor, Arnt, or
other ligand bonding or enzymatic relationships. Given the extreme
variability in response in laboratory animals, it is advisable that the
toxicity equivalency factor (TEF) approach not be used across all
species until a more robust evaluation of adverse effects across taxa is
completed. The Van den Berg et al (1998) paper does not address adverse
effects specifically.

-2-

b\. The TEF method appears to be valid for extrapolation of relative
risk to fish. The document provides an excellent description of the
dioxin TEF/TEC approach that, until now, has been used for ecological
risk assessments but never explained in this detail. Technically, the
guidance provides the most scientifically valid approach that exists for
evaluating mixtures of dioxins and dioxin-like compounds for risks to
fish. This document provides additional guidance for the proper use of
these TEFs within ecological risk assessment. Although there are several
weaknesses in the approach as acknowledged on page 66, it is currently
the most scientifically valid of the approaches that exist.

c\. The title of this document is misleading. It leads the reader to
believe that this will be an overview of the Toxicity Equivalence
Methodology, in much the same way as the Van den Berg et al (1998)
presentation. Rather, the document adds a summary of the ERAGS process
and would more appropriately be titled something such as "Ecological
Risk Assessment of PCDDs, PCDFs, and Dioxin-like PCBs."

d\. The proposed use of the TEC is questionable because the Van den Berg
et al (1998) paper indicates that the biological meaning of this value
is obscure. It is understood that the TEC is used to try to assess
potential additive effects of a mixture, but this does not appear
appropriate for all ecological receptors given our lack of knowledge on
how toxicity is occurring.

The following people were involved with the review of this document, Dr.
Mark Johnson (USACHPPM), Ms. Lia Gaizick (USACHPPM), Mr. Terry Walker
(USACE, Hazardous, Toxic and Radiological Center of Expertise), Dr. Jeff
Steevens (USACE ERDC), and Mr. Lawrence Tannenbaum (USACHPPM). The
technical point of contact for this topic is Dr. Mark Johnson who can be
reached at (410) 436-5081. Ms. Laurie Haines, the Army BTAG Coordinator,
can be reached at (410) 436-1512.

Sincerely,

Randall J. Cerar

Chief

Cleanup Division

Enclosure

**US ARMY COMMENTS AND RECOMMENDATIONS**

On the

Framework for Application of the Toxicity Equivalence Methodology for
Polychlorinated Dioxins, Furans, and Biphenyls in Ecological Risk
Assessment, External Review Draft

USEPA Risk Assessment Forum, Washington DC, June 2003 EPA/630/P-03/002A

# *USEPA Docket Number: ORD-2003-0002*

1\. General Comments, M. Johnson:

The Toxicity Equivalency Factor (TEF) approach is designed to provide a
means to evaluate the risk of exposure to substances that lack a
pertinent and complete set of toxicity data. Briefly, relative
differences in toxicities of a substance that has a complete set of data
(e.g., TCDD) are compared to other substance(s) that share a similar
chemical structure. Relationships are determined through an evaluation
of Ah receptor binding affinity, metabolism induction, or a host of
other potential responses. Studies that were used to help address a
portion of these processes were all used for comparison purposes.

This assessment professes to know the mechanism and that it is entirely
mediated through the Ah receptor. This is not true. Strong evidence
exists that TCDD and other molecules of similar structures act through
Ah ligand binding that affects gene transcription. The possibility that
the Ah receptor may form different heterodimeric complexes with proteins
other than Arnt has been described in other EPA publications and has
been suggested may help explain the diversity of dioxin-type effects.

Variation in effects between species is incredible and noteworthy,
particularly within the class Mammalia. To suggest a single TEF would be
representative of an entire class of vertebrates is not defensible.
Intraperitoneal TCDD LD50's range from 500 ng/kg in the guinea pig to \>
3 mg/kg in the hamster. These acute values range more than five orders
of magnitude. Sub-lethal data suggest even greater variation. Other EPA
publications have recognized that there are currently insufficient data
to develop the TEF approach for non-carcinogenic benchmark development
for humans (EPA 2000), how can this publication support the use of such
an approach for many species for which there are limited data?

This framework relies heavily upon the Van den Berg et al. (1998)
results. Here, few oral dose/response data are used, particularly for
birds. The avian data rely almost exclusively upon MFO induction and
correlations with other congeners using egg injection and *in vitro*
assays. Although these relationships suggest differences of Ah binding
affinity within controlled conditions, they fail to provide
dose/response information relevant to oral exposures, nor do they
consider other variations in genetic transcription activity
relationships that may vary between species and congeners. There are
other attributes that are each part of the mechanism of TCDD toxicity
that are

Enclosure

not evaluated or even discussed. In other words, Ah receptor binding
affinity cannot describe the entire variation within the mechanism of
toxicity, particularly for species within a class that have not yet been
tested. Dose/response data of the same congener (i.e., TCDD) can be
highly species-specific and variable (Peterson et al. 1993).

To conclude, methods and the data to usefully quantify
*non-carcinogenic* risk from TCDD, congeners, and other specific
co-planar PCBs are lacking and too variable for use, presently. Given
the extreme variability in response in laboratory animals, it is
advisable that extrapolation be mechanistic-based and the TEF approach
not be used across all mammalian classes.

2\. General Comment, L. Tannenbaum

[Comment]{.underline}: Based on its title, the subject document gives
the impression that it has much information to offer. Instead it merely
reminds the reader of what are, by this time, well-established concepts
that can be found in numerous other risk assessment-related guidance
(such as the notion that similar compounds can have very different
toxicities, etc.). The subject document provides much unnecessary
information that is not germane to the topic. In other words, from the
title and the preface of the document, the reader is aware (or should
be) that the subject matter is to address the phenomenon of how to
assign appropriately weighted toxicities to various polychlorinated
compounds. Consider then, how unnecessary it is to have a *description*
[and]{.underline} a *diagram* of an aquatic food web. Also, consider how
unnecessary it is to have Equation 3-8 (for gull eggs; page 42) after
the identical Equation 3-7 is provided (for trout eggs; page 41). An
example of information provided that is not germane to the topic is the
discussion on Hazard Quotients (HQ). Again, the thrust of the document
should have been on assigning toxicity to compounds; it should not
provide a review on how to calculate risks or hazards after some toxic
equivalencies have been provided, and it should also not then provide a
discussion on HQ limitations. The document is rather obviously
duplicative of other EPA guidance, and gives the reader the sense that
excess information was included so that the finished product would be
sufficiently thick to justify its place as a purported technical guide.

[Recommendation]{.underline}: Consider not finalizing the subject draft
document until such time as developed technical information exists that
addresses the points raised in General Comment #1. See Comments #s 10,
32, 33, and 35.

3\. General comments, L. Gaizick

The majority of information provided in this document is information
that has been presented in other EPA guidance (i.e., Peer Review Draft
Screening Level Ecological Risk Assessment Protocol for Hazardous Waste
Combustion Facilities, USEPA 1999). However, it is unusual that the 1999
guidance document is not referenced in the current document. The
necessity of this framework is questionable since it has already been
presented elsewhere by USEPA. It is also questionable that the toxicity
equivalence methodology has not changed since the 1999 USEPA guidance
document was published, given how much we know about the uncertainty in
trying to apply TEFs across mammalian species. It is surprising that EPA
is still recommending that TEFs be used for all species of mammalians
and avians (see General comment #1).

Additionally, the title of this document is misleading. It leads the
reader to believe that this will be an overview of the Toxicity
Equivalence Methodology, in much the same way as the Van den Berg et al
(1998) presentation. Rather the document adds a summary of the ERAGS
process and would more appropriately be titled something such as "The
Eight-step process for Ecological Risk Assessment of PCDDs, PCDFs, and
Dioxin-like PCBs".

4\. General comment, T. Walker

The discussion of uncertainty will be immensely helpful when assessing
this type of risk.

5\. Page vi, L. Tannenbaum

Preface

[Comment]{.underline}: The first sentence is poorly worded.

[Recommendation]{.underline}: Please have the sentence end with: " . . .
including animal tissues." Note the wording of the end of the
"Introduction's" first sentence.

6\. Page 1, Section 1, L. Tannenbaum

Introduction

[Comment]{.underline}: The third sentence may be misleading the reader.
Although demonstrated toxic effects of 2,3,7,8-TCDD may be known for the
various animal groups listed here, these no doubt have [not]{.underline}
been associated with any contaminated (i.e., hazardous waste) site. The
sentence is almost certainly referring to effects identified [in nature
at large]{.underline}, and not to specific "managed" (contaminated)
sites. See Comment #18.

[Recommendation]{.underline}: If the subject document is to be finalized
in its premature state (see Comment #2), please modify the text here to
make it clear that there have yet to be observable effects from TCDD in
birds and mammals at contaminated sites. Please have the text here also
mention that there have yet to be any debilitating effects observed in
birds or mammals at any contaminant site, and independent of the
chemical(s) found there. A useful reference to cite in the revised
paragraph is [Tannenbaum, L.V., 2003. Can Ecological Receptors Really Be
At Risk? Human and Ecological Risk Assessment, Volume 9(1):
5-13]{.underline}.

7\. Page 3, Section 1.1, L. Tannenbaum

Definitions

[Comment]{.underline}: It is most curious that there is an expanded
discussion about the central acronym "TEF", yet the spelled out term
appears nowhere on the page. Note that it is only on page 4 that "TEF"
is defined.

[Recommendation]{.underline}: Please consider providing the spelled out
term (for TEF) on page 3. Note that given the information in Text Box 1,
one could think that "TEF" stands for "Toxicity Equivalence Factor",
"Toxicity Equivalency Factor", Toxic Equivalent Factor", etc. Also,
nowhere is it alluded to on page 3 that the "F" in "TEF" stands for
"factor".

8\. Page 3, Section 1.1, L. Gaizick

[Comment]{.underline}: In this section the term TEC (toxicity
equivalence concentration) is not presented, but should be.

[Recommendation:]{.underline} Include the definition of TEC in this
section.

9\. Page 6, L. Tannenbaum

Table 1

[Comment]{.underline}: Neither the table nor the text on the page makes
it clear how the table's last two columns relate to one another. What is
the difference between a "congener" and a "dioxin-like congener"? Also,
does the last column really mean to say that there are "furan-like
congeners" and also "biphenyl-like congeners"? Are the "dioxin-like
congeners" the primary concern of the subject document? If so, why isn't
this reflected in the title? Last (and perhaps most important), the last
column of information does not jive with the text of the page's last
paragraph. Specifically, the [text]{.underline} refers to 7, 10, and 12
[TEFs]{.underline} as corresponding to the three chemical classes. The
[table]{.underline} however, says nothing about TEFs, and instead causes
the reader to interpret the table two ways, neither of which is probably
correct. As an example, does the table mean to convey that of the 75
dioxin congeners, that 7 are "dioxin-like", or does the table mean that
in addition to there being 75 dioxin congeners, there are another 7 that
are "dioxin-like" ones?

[Recommendation]{.underline}: If the document is to be finalized, please
make the necessary textual modifications to address the points raised in
the Comment.

10\. Page 9, Section 2, L. Tannenbaum

The Toxicity Equivalence Methodology

[Comment]{.underline}: Realistically, the subject document could be
reduced to a few pages, because almost the entire document is of
information that is not germane to the title of the document (e.g.,
discussion of a conceptual site model, etc). The sole purpose of the
subject document is to instruct the reader on how to construct the
all-important concentration term, where dioxins, furans, or PCBs occur
in environmental media, so that doses (intakes) can be computed. Also, a
question arises of there even being a need for a guidance document, if
what it intends to say is so brief, with very little original matter.
The truth is that TEM amounts to a series of considerations (that are
listed here as bullet points). The following points that relate to
several of the bullet points should be noted. Regarding the first bullet
point, a simple 'yes-no' determination is needed (i.e., is the chemical
one that acts through the AhR receptor or not?). Regarding the next two
bullet points, the reader was expecting that new, and yet-to-be seen,
potency estimates would be presented. Instead, the subject document
essentially recommends using several long-time existing datasets. This
prompts the question: "What then is the subject document telling the
reader that he/she doesn't already know?" The last two bullet points are
disturbing. They do not talk to the issue of toxicity equivalence;
instead they relate to constructing a concentration term for a risk or
hazard model.

[Recommendation]{.underline}: Please consider the various points made in
the Comment. Consider changing the subject document to an OSWER
directive rather than a guidance document. Such a directive could state
the present EPA policy, namely that the Van den Berg et al (1998) values
are deemed legitimate by EPA, but that an option exists to develop other
site-specific RPF.

11\. Page 10, Section 2.1, L. Tannenbaum

Ah Receptor Mediated Mechanism and Assignment of Relative Potency

[Comment]{.underline}: The page's first full paragraph discusses the
scientific defensibility of the "second assumption". Seemingly there is
earlier discussion on the scientific defensibility of a first
assumption. What is the first assumption, and where is the discussion on
it?

[Recommendation]{.underline}: Please restructure the beginning of
Section 2.1 for parity with page 10's first full paragraph.

12\. Page 10, Section 2.1, L. Tannenbaum

Ah Receptor Mediated Mechanism and Assignment of Relative Potency

[Comment]{.underline}: Given the third listed criterion (i.e., the
page's third bullet point) for including a compound in the TEM (namely
that there is demonstrated binding to the AhR), it appears that the
second criterion (namely that there is demonstrated ability to elicit an
AhR-mediated effect) is moot.

[Recommendation]{.underline}: If the subject document is to be
finalized, please consider deleting the second TEM criterion because it
is contained within the third listed one.

13\. Page 11, Section 2.1, L. Tannenbaum and L. Gaizick

Ah Receptor Mediated Mechanism and Assignment of Relative Potency

[Comment]{.underline}: The page's first sentence is not understood.
Doesn't TEM equally apply to furan-like and PCB-like compounds as it
does to dioxin-like compounds? Is this first sentence referring back to
the information that is presented in Table 1 (see comment #6)?
Additionally, the second sentence is also troublesome because it lacks a
clear example. Is it referring to Aroclors?

[Recommendation]{.underline}: Please consider revising the sentence to
address the concern expressed in the Comment. The second sentence should
provide an example of what the "other PCBs" being referred to can
consist of.

14\. Page 12, Section 2.2, L. Tannenbaum

Selection of the Appropriate Potency Factors

[Comment]{.underline}: The Section's first sentence is surprising.
Shouldn't it say that "the decision regarding what relative potency
values to use for each chemical" is "the" most important consideration?

[Recommendation]{.underline}: Please reword the sentence as suggested in
the Comment.

15\. Page 12, Section 2.2, line 21, L. Gaizick

Selection of the Appropriate Potency Factors

[Comment:]{.underline} The text states that "An RPF may be derived from
a data base of ReP values", yet the text does not reference any
database. Does a database exist? This statement is somewhat misleading
because isn't the majority of information that we have already presented
in the Van den Berg et al (1998) paper?

[Recommendation:]{.underline} It may be more appropriate to remove the
text about a database of ReP values, unless a reference can be provided
for a database. If this text is meant to indicate a future data
compilation it may be better presented by saying a project (or site) -
specific database.

16\. Page 13, Section 2.3, L. Gaizick

Toxicity Equivalence Concentration

[Comment:]{.underline} The proposed use of the TEC is questionable
because the Van den Berg et al (1998) paper indicates that the
biological meaning of this value is obscure. It is understood that the
TEC is trying to assess potential additive effects of a mixture, but
this does not appear appropriate for all ecological receptors given our
lack of knowledge on how toxicity is occurring.

[Recommendation:]{.underline} See general comment #1.

17\. Page 13, Section 2.3, L. Tannenbaum

Toxicity Equivalence Concentration

[Comment]{.underline}: The Section should simply state that
operationally, the TEF is multiplied by the concentration of the
congener (in an organism or in its food). The Section should
[not]{.underline} accentuate that a dose term or tissue concentration
term is being developed, because this shifts the discussion to that of
risk and hazard computation, something that is removed from TEM.

[Recommendation]{.underline}: Please remove all references here to the
development of dose terms.

18\. Page 15, Section 3.1, L. Tannenbaum

Considerations in Planning

[Comment]{.underline}: The second paragraph is misleading. The commenter
challenges the suggestion that observed adverse effects in fish,
fish-eating birds, and mammals can ever definitively be shown to be
attributable to PCDD, PCDF, or PCBs.

[Recommendation]{.underline}: Please rewrite the paragraph so as not to
give the reader a false sense that we have the capability to identify
specific compound-triggered toxicity in the receptors. Also, in the
rewritten paragraph, indicate that given the sizes of sites at which
ecological risk assessments are conducted, there really is no chance to
observe adverse effects. Consider how many birds or mammals of a given
species are to be found at a given hazardous waste site that is almost
always far less than 20 acres.

19\. Pages 19-20, Section 3.2.1.1, L. Tannenbaum

Susceptibility: Sensitivity

[Comment]{.underline}: The discussion here is disturbing for two
reasons. One implication is that the reported instances of dioxin-like
toxicity are from studies at contaminated sites, when in fact they are
from research studies. Second, by providing the list of relatively
insensitive species (to TCDD), the (false) sense is created that had
these species been found to be sensitive, that cleanup considerations
might be an issue.

[Recommendation]{.underline}: Please delete the list of invertebrates
because even had these species been demonstrated to be sensitive, it is
clear that contaminated site cleanups never proceed on the basis of
effects in worms, snails, mosquito larvae, and the like.

20\. Page 21, Section 3.2.1.2, L. Tannenbaum

Table 3

[Comment]{.underline}: The first row of information (i.e., "Presence of
AhR") does not belong in the table. The table covers "effects of TCDD
and related compounds in different animal species", and "presence of
AhR" is not an effect but rather a cellular feature.

[Recommendation]{.underline}: Please delete the first row from the table
because it relates to information that the table is not addressing.

21\. Page 22, Section 3.2.1.2, L. Tannenbaum

Susceptibility: Exposure

[Comment]{.underline}: The reference to "greatly reduced
bioaccumulation" at the end of the page's second sentence requires
qualification.

[Recommendation]{.underline}: If the subject document is to be
finalized, please clarify if the identified phrase is referring to a
lesser opportunity to load PCDDs, or to lesser bioaccumulation due to
greater opportunities for clearing of PCDDs (as occurs when the animal
is away from the contaminated site).

22\. Page 24, Section 3.2.2, L. Tannenbaum

Conceptual Model

[Comment]{.underline}: The subject document does not need a treatment of
conceptual models. It is understood that if certain dioxin-like
compounds should be in environmental media, ecological receptors could
directly or indirectly contact them.

[Recommendation]{.underline}: Please delete the treatment that spans
pages 24 through 26.

23\. Pages 28 --35, Sections 3.3 3.3.1.4, L. Tannenbaum

Considerations in Analysis, etc.

[Comment]{.underline}: The topics dealt with in these pages are
unnecessary. Again, the subject document should be addressing relative
toxicity or potency of dioxin-like compounds.

[Recommendation]{.underline}: In the revised document, please remove all
references to contaminant fate and transport considerations, and choices
of exposure dose metrics. In place of the information that doesn't
belong here, consider having the revised document say that numerous
USEPA ERA guidance documents abound with information regarding
contaminant fate and transport, and exposure dose metrics.

24\. Page 32, Section 3.3.1.3, L. Tannenbaum

Choices for the Exposure Dose Metric

[Comment]{.underline}: The last sentence of the page's first full
paragraph raises a serious question. Given the vast imprecision in
estimating contaminant concentrations in the tissues of organisms, is it
really worthwhile to put additional energies into refining TEFs and the
like?

[Recommendation]{.underline}: Please have the uncertainty section
discuss the question raised in the Comment. Have the text note here and
in several other places, that only ERA [screening]{.underline} is being
discussed, and therefore since field-truthing will likely follow,
precision is [not]{.underline} something that's needed for TEM. See
Comment #35.

25\. Pages 36 to 38, Section 3.3.1.4, L. Tannenbaum and L. Gaizick

Tables 4, 5, and 6

[Comment]{.underline}: There is no need to provide three examples of
estimating TECs, especially when the columns of all three tables are
identical in design, unless the values presented in the BSAF column for
each receptor are expected to be used in any risk assessments performed
using these receptors.

[Recommendation]{.underline}: Please delete Tables 5 and 6 because they
are so duplicative. In the text, please explain how the columns in Table
4 were calculated and indicate in the text how the values would be
calculated for other receptors.

26\. Page 43, Section 3.3.1.5, L. Tannenbaum

Examples of TEC Calculations for Fish, Birds, and Mammals

[Comment]{.underline}: The text references Figures 7 and 8 that "show
the relative contributions to the TECs made by PCDDs and PCDFs in
comparison to PCBs for trout and gull eggs, respectively." This sentence
construct is basically not intelligible to the reader. Additionally,
from what *can* be understood, what need is there to provide such a
"break-out" of relative contributions to the TECs? Relative
contributions to the TECs don't appear to be a reflection of
differential toxicity or potency. Is the text suggesting that they are?
Please note that based on the title, the subject document is supposed to
address the differential toxicity of PCBs, PCDDs, and PCDFs. It is not
supposed to be addressing differential chemical concentrations in the
various media.

[Recommendation]{.underline}: Please address all the points and
questions raised in the comment.

27\. Page 46, Section 3.3.2, L. Tannenbaum and L. Gaizick

Selection of TEFs or RPFs

[Comment]{.underline}: The page's last sentence is saying that TEFs
developed for humans are largely applicable to ecological receptors. How
is this known? Additionally, this Section devotes several pages to
discussing how to derive RPF. This text makes it seem that there is data
out there on the relationship of congener toxicity to that of TCDD.
References should be provided if there is new data available that the
EPA is suggesting be utilized. If there is no new data, then this text
is inappropriate because unless there is a great deal of funding in a
CERCLA risk assessment then most likely enough studies will not be
funded to derive an RPF. Additionally, the text on page 47 is confusing
in that it states that "if RPFs can be derived from RePs for relevant
effects to a particular species of concern in an ecological risk
assessment, they may be more accurate in calculating TECs than TEFs,
which are consensus values for entire taxonomic classes of organisms".
The confusion is that on page 57 it states that RPFs are TEFs.

[Recommendation]{.underline}: Please extract critical points from the
Van den Berg (1998) citation to support the statement, and present them
here. The text on page 47 should indicate that derived RPFs are more
accurate than the WHO-TEFs.

28\. Page 48, Section 3.3.2.1, L. Tannenbaum

General Considerations for Selecting RPFs

[Comment]{.underline}: The Section mentions "high quality" ReP data.
What is the definition of "high quality" data in this context?

[Recommendation]{.underline}: Please qualify/define the term "high
quality" as it is used.

29\. Pages 49-50, Section 3.3.2.2, L. Tannenbaum

Visualization and Application of Criteria for Selection of Optimum RPFs

[Comment]{.underline}: The text describing the three dimensional matrix
model for the selection of RPFs or TEFs is excessive. Additionally, it
may be that Figure 10 is unnecessary, even if the text that corresponds
to the Figure were to be reduced.

[Recommendation]{.underline}: Please greatly reduce the discussion
pertaining to the model. If the Figure is to remain, endeavor to
simplify/streamline it. Consider using either "tiers" or "levels" for
all three axes (i.e., endpoint specificity, species specificity, dose
specificity), and not a mixture of these terms.

30\. Page 56, Section 3.3.2.3, L. Tannenbaum and L. Gaizick

Table 7

[Comment]{.underline}: The reader finds this Figure far too hard to
follow. Additionally, it is questionable why an ReP is presented in the
Table rather than an RPF. Why can an RPF be based on a single study? It
would seem that less uncertainty might be associated with the consensus
value (WHO-TEF) rather than a value based on a single study.

[Recommendation]{.underline}: Please consider replacing the Figure with
an easier example to follow. Simply list, in bullet point fashion, the
critical pieces of information that are known to the risk assessor, and
indicate the choices available to him/her for optimizing species and
endpoint specificity.

31\. Page 60, Section 3.3.2.4, L. Tannenbaum

Table 8

[Comment]{.underline}: The term "EROD induction" appears several times,
but is not coined here or anywhere else in the document.

[Recommendation]{.underline}: Please define the term in its first usage.
Also consider defining the term in the glossary. See Comment #37.

32\. Pages 62 and 63, Section 3.4.1, L. Tannenbaum and L. Gaizick

Risk Estimate

[Comment]{.underline}: Equation 3-9 is not one that gives rise to a
"risk" estimate. It rather depicts a "hazard" calculation. See Comment
#36. Additionally, no reference is cited for the TCDD toxicity reference
value.

[Recommendation]{.underline}: Please consider deleting all mention of
quotient methods, as these do not relate to the document's purpose. If
the present language is to remain, consider adding the following
reference regarding quotient method limitations ([Tannenbaum, L.V.,
Johnson, M.S., and Bazar, M., 2003. Application of the Hazard Quotient
Method in Remedial Decisions: A Comparison of Human and Ecological Risk
Assessments. Human and Ecological Risk Assessment, Volume 9 (1):
387-401]{.underline}). This reference provides a comprehensive review of
quotient method limitations, and particularly within ERA. Additionally,
if so much information has been presented on other aspects of risk
assessment, a TCDD Toxicity Reference Value should be included in this
document. At a minimum, citations to where TCDD TRVs can be found should
be provided, including previous EPA guidance documents (USEPA 1999).

33\. Pages 63 to 65, Section 3.4.2, L. Tannenbaum

Lines of Evidence

[Comment]{.underline}: The material of these pages has nothing to do
with toxicity equivalence. Although field-truthing is a component of
ERA, it is irrelevant in the discussion. Similarly the discussion on
toxicity tests and other bioanalytical tools only burden the reader with
material that does not relate to TEM, and that can be found described in
numerous other USEPA ERA guidance documents.

[Recommendation]{.underline}: Please delete the text of pages 63 to 65.

34\. Page 63, Text Box 6, T. Walker

[Comment:]{.underline} Text Box 6 is not complete and precedes Text Box
5 (page 64).

[Recommendation:]{.underline} Edit the text to address the Comment.

35\. Page 65, Section 3.4.3, L. Tannenbaum

Summary of Uncertainties

[Comment]{.underline}: The Section's third sentence should be rewritten
for clarity.

[Recommendation]{.underline}: Please consider the following rewrite: ".
. . the toxicity equivalence methodology, in aggregate, they are
believed to be less significant than those associated with other aspects
. . . "

35\. Pages 67 and 68, Section 3.4.3.1.4, L. Tannenbaum

Point Estimates

[Comment]{.underline}: This Section's last paragraph is rather damaging
to the subject document. The text is avowing that the uncertainty
surrounding the TEFs and RPFs is so great that it would be better to
perform TEC calculations with a range of RePs, etc. Such a suggestion
only serves to underscore how premature it is to be issuing the subject
guidance when the reliability associated with the methodology is so
questionable.

[Recommendation]{.underline}: Please consider not finalizing the subject
document, given that the science is not well enough developed to render
reliable assessments, even within a context of ERA screening.

36\. Page 70, Section 3.4.3.2.3, L. Tannenbaum

Uncertainties in risk characterization

Comment: The term "risk estimate" is used several times here. The text
however, is referring to (hazard) quotients, which are not estimates of
risk. The quotients alluded to here are rather [measures of levels of
concern]{.underline}. The correct word to substitute for "risk"
throughout this Section is "hazard".

[Recommendation]{.underline}: Please replace "risk" with "hazard"
throughout the Section.

37\. Pages 82 to 84, L. Tannenbaum

Glossary

[Comment]{.underline}: A number of other terms should be added to the
glossary for completeness, and to assist the reader.

[Recommendation]{.underline}: Please consider adding: AhR agonist,
homolog, and homolog group(s). Please screen the subject document fully
for other technical terms that rightfully should be defined in a
glossary.

References

Peterson RE, Theobald HM, Kimmel GL. 1993. Developmental and
reproductive toxicity of dioxins and related compounds: cross-species
comparisons. Critical Reviews in Toxicology 23(3):283-335.

U.S. Environmental Protection Agency. 2000. Exposure and Human Health
Reassessment of 2,3,7,8-Tetrachlorodibenzo-*p-*Dioxin (TCDD) and Related
Compounds. EPA/630/P-03/002A. U.S. EPA Risk Assessment Forum, Washington
D.C. (draft).

Van den Berg M, Birnbaum L, Bosveld ATC, et al. 1998. Toxic equivalency
factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.
Environmental Health Perspectives 106(12):775-792

USEPA. 1999. Screening Level Ecological Risk Assessment Protocol for
Hazardous Waste Combustion Facilities, Peer Review Draft. August 1999.
SWER EPA530-D-99-001C.