r/EPA
             United States
             Environmental Protection
             Agency
Office of Water (WH-586)
Office of Science and Technology
Washington, DC 20460
                           EPA-822-R-93-OO6
                           July 1993
Wildlife Criteria      a
Portions of the       \,
Proposed Water     ^
Quality Guidance for
the Great  Lakes
System
                                          £CV:-i
                                           Printed on Recycled Paper

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                   \
 PROTECTION
   AGENCY
       r          EPA-822-R-93-006
      , TEXAS              July 1993

OBRARY
        Wildlife Criteria Portions
       of the Proposed Water Quality
    Guidance for the Great Lakes System
      Office of Science and Technology
             Office of Water
United States Environmental Protection Agency
         Washington, D.C. 20460

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                                      DISCLAIMER

This document has been reviewed by the Health and Ecological Criteria Division, Office of Science
and  Technology, U.S.  Environmental  Protection Agency,  and was published  in  the  Federal
Register. Friday, April 16,  1993 as part of the "Water Quality Guidance for the Great Lakes
System and Correction; Proposed Rules." Publication does not signify that the contents necessarily
reflect the views and policies of the U.S. Environmental Protection Agency or of any other
organization or agency represented by the authors of, or contributors to, this document.  Mention
of trade names and commercial products does not constitute endorsement of their use.
                                AVAILABILITY NOTICE

Limited copies of this document,  Wildlife  Criteria  portions of the Proposed Water  Quality
Guidance for the Great Lakes System, are available upon request from:


                             Water Resource Center (RC-4100)
                                   401 M. Street, S.W.
                                 Washington, D.C. 20460
                                      202/260-7786

The contents of this document make up a portion of the document listed here: 40 CFR parts 122
et al.  Water Quality Guidance for the Great Lakes System and Correction; Proposed Rule.  For
individuals interested in the entire Great Lakes Water Quality Initiative, we suggest ordering the
document listed in this paragraph.  This document is available for a fee upon written request or
telephone call to:

                       National Technical Information Service (NTIS)
                              U.S. Department of Commerce
                                  5285 Port Royal  Road
                                  Springfield, VA  22161
                                     (800) 553-6847
                                     (703) 487-4650
                                NTIS Document Numbers:
                               Diskette Set:  PB-93-504-504
                               Paper Copy: PB-93-164-515

                                           or

      Education Resources Information Center/Clearinghouse for Science,  Mathematics, and
                         Environmental Education (ERIC/CSMEE)
                             1200 Chambers Road,  Room 310
                                  Columbus, OH 43212
                                     (614) 292-6717
                                     ERIC Number:
                                   Diskette Set: 526D
                                   Paper Copy: 527D

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                                    PREFACE

    Wildlife criteria are unique among the criteria proposed within the Great Lakes Water
 Quality Initiative (GLWQI) Guidance because the U.S. Environmental Protection Agency
 has not yet issued any nationally applicable criteria focused specifically at the protection of
 wildlife.  This  document was  produced to facilitate review of and comment  on the
 proposed  wildlife criteria approach by persons who may not keep abreast of Federal
 Register notices, including the larger scientific community.   Because there is  not  an
 established national  approach,  national  guidance may eventually be modeled  on the
 proposed GLWQI Guidance.

    The U.S. Environmental Protection  Agency will accept public comments  on the
 proposed GLWQI Guidance until September 13, 1993 (see Appendix A for details).  The
 Preamble to the proposed rule (Chapter 1 of this document) specifically invites comments
 on the modification of this approach for development of  a national wildlife  criteria
 procedure.  Since these comments would be used for an effort outside the scope of the
 GLWQI,  commenters need not feel constrained  by the deadline within that proposal.
 Comments on the modification  of the GLWQI approach for development of a national
 wildlife  criteria can be  sent  at any  time  to:    Wildlife Program  (WH-586)/U.S.
 Environmental Protection Agency/401 M. St., S.W./Washington, D.C. 20460.

    This document is composed of five chapters and two appendices.  Chapter 1 describes
 the development of the  proposed wildlife  criteria procedure;  Chapter  2 presents the
 proposed  wildlife  criteria  methodology; Chapter  3  presents  the Technical Support
 Document for the development of wildlife criteria; Chapters 4 and 5 present sections from
 the implementation procedures  which may impact the wildlife criteria.   Appendix A is
 introductory material from  the Federal Register notice  and includes the address where
 comments should be sent; Appendix B is an appendix to a separate document, Great Lakes
 Water  Quality Criteria Initiative Technical Support Document for Human Health Criteria
 and  Values,  and is  included because it is frequently cited in  the  main text  of this
 document.  Chapters  1 and 4 are excerpted from the Preamble to the GLWQI, Chapters 2
 and 5  are excerpted  from Appendices to the GLWQI proposed rule, and Chapter  3 is
 published as an Appendix to the  Preamble in the Federal Register notice.

    There is  a companion  document  to  this  one entitled Great Lakes Water  Quality
Initiative Criteria Documents for the Protection of Wildlife (PROPOSED): DDT; Mercury;
2,3,7,8-TCDD; PCBs. The criteria document contains the derivation of the actual wildlife
criteria values proposed in  the  GLWQI  and may be obtained from National Technical
Information Service (NTIS Document Number:  PB93-154722) or the Education Resources
Information Center/Clearinghouse for Science, Mathematics, and Environmental Education
 (ERIC/CSMEE Document Number 397D).

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 Contents
  We recognize there are inconsistencies in the outline format among the chapters in this
  document. This is because we maintained the outlines used in the Federal Register to
  facilitate comparisons between this document and the Federal Register notice.
 CHAPTER 1
 Section VT   Prible to Gr      k
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CHAPTER 3 (Continued)
IV.   Parameters of the Exposure Component of the Wildlife Criteria
      Methodology                                                         34
V.    Determination of Species Identified for Protection and Associated
      Exposure Parameters         .                                         34
VI.   References                                                          42
CHAPTER 4
Portions of Section Vm of Preamble to Great Lakes Water Quality Guidance: General
Implementation procedures

A.    Site-Specific Modifications to Criteria                                    45
D.    Additivity                                                           51
CHAPTERS
Portions of Appendix F to Part 132-Great Lakes Water Quality Initiative Implementation
Procedures	

Procedure 1: Site Specific Modifications to Criteria/Values                        66
Procedure 4: Additivity                                                     67
APPENDICES	

Appendix A: Introductory material and outline from Preamble to Great Lakes Water
      Quality Guidance package                                              A-l
Appendix B: Appendix A: Uncertainty Factors in Great Lakes Water
      Quality Criteria Initiative Technical Support Document for Human
      Health Criteria and Values                                             B-l

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 CHAPTER 1
       Section VI of Preamble to Great Lakes Water Quality
 Guidance: Wildlife

 A. Introduction

        For the purposes of the proposed Great Lakes Water Quality Criteria Guidance,
 "wildlife" is defined as species in both Taxonomic Classes, Aves and Mammalia (birds and
 mammals).  The proposed Guidance for deriving wildlife criteria and values is included in
 appendix D of the proposed Guidance. The Technical Support Document for Wildlife
 Criteria is an appendix to this preamble.  The actual criteria documents which provide the
 data and the derivation of the individual criteria are available in the administrative record for
 this rulemaking.  EPA's expectations for determining whether a State's water quality
 standards are consistent with the Guidance are set forth in § 132.6 of the proposed Guidance.

       In the case of toxic chemicals, terminal predators such as otter, mink, gulls, terns,
 eagles, ospreys and kingfishers are at risk from contaminants in Great Lakes waters.  In
 addition to direct exposure via drinking the water, species at higher trophic levels are
 exposed to toxic substances through the food web as the chemicals proceed upward via
 biomagnification. Contaminants which are almost undetectable in lake water may be
 magnified hundreds of thousands of times within the flesh of fish and magnified still further
 in a carnivorous bird or mammal which consumes contaminated fish out of the Great Lakes.

       Because wildlife species are at the top of the food web, current criteria derived to
 protect fish, which live in the water, may be inadequate to protect high-level wildlife
 consumers of contaminated fish. Wildlife are especially at risk from  chemicals which
 biomagnify because they are  frequently exposed to very high levels of the contaminants since
 they reside at the apices of aquatic food webs.  For this reason, emphasis was placed on
 selecting piscivorous wildlife species (i.e., those which eat fish) for the derivation of wildlife
 criteria as representative of species likely to  experience significant contamination through an
 aquatic food web.  Wildlife species may also have unique  metabolic pathways which make
 them more susceptible to the toxicity of a chemical than aquatic species.

      Research on wildlife species resident  in the Great Lakes indicates that wildlife
populations are threatened in areas of high contamination by toxic chemicals. In the Great
Lakes, reproductive impairment of numerous wildlife species has been correlated with the
presence of PCBs, DDT and  its metabolites, and other contaminants.  In the 1960s, mink fed
a diet of Great Lakes fish suffered complete  reproductive failure. Detailed laboratory
investigation revealed that the causative agent was PCBs in Great Lakes fish. The overall
reproductive success of bald eagles is much lower along lake shore areas of the Great Lakes
than in inland nesting territories.

      There is additional discussion located in the section I (Background) of this preamble
on the impacts of toxic chemicals on wildlife in the Great  Lakes.  Numerous studies confirm
the adverse effects of pollution on Great Lakes wildlife and support the need for water

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quality criteria formulated for their protection.  It is because of the numerous impacts of
toxic chemicals observed in wildlife in the Great Lakes and the inconsistencies among the
Great Lakes States and Tribes in addressing wildlife impacts, that the Steering Committee,
Technical Work Group, and EPA agreed there was a need for generation of separate wildlife
criteria as a part of the Great Lakes Water Quality Initiative (GLWQI).  This provides the
rationale for proposing specific wildlife standards in this Guidance.

      EPA has ample authority to develop criteria and methods  specifically directed at
protecting wildlife from threats originating in Great Lakes waters.  Section 118(c)(2)(A) of
the Clean Water Act requires EPA  to develop numerical limits on pollutants in Great Lakes
waters to protect wildlife as well as human health and aquatic life. Similarly, provisions of
the Great Lakes Water Quality Agreement of 1978 require the United States and Canada to
protect wildlife. For example, Article HI of the Agreement established a "General
Objective" of freeing the Great Lakes System from substances resulting from human activity
that will  adversely affect waterfowl.

      Moreover, several of the "Specific Objectives" for individual pollutants set out in
Annex I  of the Agreement also set limits which should not be exceeded in order to protect
fish-consuming birds and animals.  These are presented as fish tissue concentrations or water
concentrations as follows: DDT and its metabolites in whole fish should not exceed 0.3
micrograms per gram (wet weight basis), the concentration of total PCBs in whole fish
should not exceed 0.1 micrograms per gram (wet weight basis), and the concentration of total
mercury  in whole fish should not exceed O.S micrograms per gram (wet weight basis). The
"Specific Objectives" which present water concentrations  which should not be exceeded for
the protection  of fish-consuming birds and animals are: the total concentration of DDT and
its metabolites should not exceed 0.003 micrograms per liter; and mirex and its degradation
products  should be less than detection levels as determined by the best scientific  methodology
available.

      Section 304(a)(l) of the Clean Water Act also authorizes EPA to develop criteria that
protect wildlife for all waters of the United States. As explained in more detail later in this
section of the preamble to this rule, EPA has not yet issued any nationally applicable criteria
targeted solely at the protection of wildlife.  Rather, EPA incorporated consideration of
wildlife impacts into the 1985 methodology for developing criteria for aquatic life (Stephan,
et. al., 1985).

      The proposed Guidance relating to wildlife criteria was developed as part of the
GLWQI.  The Technical Work Group and the Steering Committee are collectively referred to
within this portion of the preamble  as the Committees of  the Initiative.  The Committees of
the Initiative assigned the lead in developing an initial proposal for deriving criteria to protect
wildlife for the Great Lakes Guidance to the State of Wisconsin.   The procedure proposed by
the Wisconsin  Department of Natural Resources was modified through discussions in the
Committees of the Initiative and modified and approved by EPA.

      In developing the methodology for deriving wildlife criteria for the GLWQI, the
Wisconsin Department of Natural Resources, Bureau of Water Resources Management,

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 obtained scientific guidance from participants in a one-day workshop (the Workshop) held in
 Madison, Wisconsin, November 8, 1990.  Wildlife research lexicologists and biologists
 representing academia, State governments, the U.S. Fish and Wildlife Service and EPA were
 invited to participate in the Workshop.  Representatives of the regulated community were
 also present at the Workshop.

 B. Wildlife Criteria Methodology

       Like the aquatic life and human health criteria methodologies described above, EPA is
 proposing a two-tiered approach for the Great Lakes Water Quality Guidance for Wildlife,
 which will hereinafter be referred to as Tiers I and n. EPA is proposing to require all Great
 Lakes States and Tribes to apply  the methodology to derive Tier I criteria and Tier n values,
 as well as the Tier I numeric criteria proposed, to discharges into the Great Lakes System.
 The Committees of the Initiative developed,  and EPA is proposing, a Tier n method that is
 very similar to the proposed  Tier I method.  However, because Tier n values are based on a
 less extensive data base than are Tier I criteria, the uncertainty factor which accounts for
 interspecies lexicological  differences (the Species Sensitivity Factor) may be smaller than that
 used in deriving a Tier I criteria.  In deriving Tier n values,  the Species Sensitivity Factor
 may also account for interspecies lexicological differences across taxonomic classes. This
 uncertainty factor is intended to address any  uncertainties stemming from the use of a less
 inclusive database and its use is meant to produce Tier n values that are conservative.

       Tier n values are intended to be conservative to encourage data generation so a Tier I
 criteria can be calculated.  Although States and Tribes have the authority at their discretion
 to do so, EPA does not intend that Tier n values will be adopted into Slate slandards, bul,
 rather, will serve as a translator mechanism  for interpretation of the State's narrative criteria
 (e.g., no toxic pollulanls in toxic amounls) and as a basis for developing conlrol measures
 such as effluent limitations in NPDES permils. In Ihe fulure, EPA  may replace Tier n
 values with Tier I criteria as more data are generated.

 1. Wisconsin Slate Wild  and Domestic Animal Criteria

       The Committees of Ihe Initiative chose, as Ihe starting point for the development of
 the wildlife criteria methodology, the Wild and Domestic Animal Criteria (WDAC) approach
 developed by the State of Wisconsin (Wisconsin Administrative Code NR 105.07, 1989;
 Technical Support Document for NR 105, 1988), which is available in Ihe administrative
 record for this rulemaking.  A WDAC is Ihe lowesl species wild and domestic animal value
 (WDAV) calculated using Ihe equation presented below.  The equation used to derive Ihe
 WDAV portrays a "model animal" as follows:

                                                   x SSF
                                       W* * (FA x BAF)

where: WDAV is the wild and domestic animal value in milligrams per liter (mg/L);
NOAEL is the no observable adverse effect level in milligrams of substance per kilogram of
body weight per day as derived from mammalian or avian studies (mg/kg-d); WtA is the

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average weight in kilograms (kg) of the test animals; WA is the average daily volume of
water in liters consumed per day (L/d) by the test animals; SSF is the species sensitivity
factor which is an uncertainty factor ranging between 0.01 and 1 to account for differences in
species sensitivity; FA is the average daily amount of food consumed by the test animals in
kilograms (kg/d); and BAF is the aquatic life bioaccumulation factor with units of liter per
kilogram (L/kg).

2.  Modifications to Wisconsin's WDAC Procedure

        As mentioned,  the proposed Guidance on a water quality criteria methodology for
wildlife is based on the  State of Wisconsin's wildlife criteria procedure.  However, the
Initiative Committees and EPA developed several modifications of this State procedure which
EPA is proposing to incorporate into the proposed Guidance. They include: a requirement
that States and Tribes  use specific Great Lakes species identified by EPA as representatives
of regional wildlife species likely to experience significant exposure from the aquatic food
web rather than using  a  "model animal"; provisions that more clearly define and make more
stringent toxicity data  requirements (i.e., a dose-response study is required); provisions
which allow a subchronic to chronic uncertainty factor to be applied to the NOAEL to
extrapolate from subchronic to chronic exposure lengths; and provisions for two tiers of
criteria rather than one as under the Wisconsin approach.  A fifth modification to the
approach submitted by Wisconsin is proposed  in procedure 1 of appendix F to part 132 of
this proposed Guidance  (the site-specific modification portion of Great Lakes Water Quality
Guidance Implementation Procedures).  Procedure 1 allows for the incorporation of an
additional uncertainty  factor into the equation to account for intraspecies variability in the
derivation of a  species-specific wildlife criterion or value for a species other than the
representative species  proposed for general use. See section Vffl.A of this preamble for a
discussion of the additional uncertainty factor in the proposed procedure 1 of appendix F, as
well as alternative text,  upon which EPA invites comment, that provides additional guidance
to States and Tribes.

3.  The Great Lakes Water Quality Initiative Wildlife  Criteria Methodology

      The approach used  in the aquatic life criteria methodology, where  the aquatic life
criterion is determined from a statistically valid distribution of toxicity values for a number
of aquatic species,  is not currently feasible for the derivation of wildlife criteria.  This is
because there is a less extensive and representative wildlife toxicity database and limited
information on  species-specific exposure parameters.  The wildlife criteria methodology is
more similar to that employed in the calculation of noncancer human health criteria.

      The general procedure as well as the requirements for developing wildlife criteria and
values are provided in appendix D to part 132.  The Technical Support Document (TSD)
provides additional background as well as guidance on the selection of values for uncertainty
factors which may be  used  in the derivation of wildlife criteria. EPA believes that the
States, the Tribes and  the public would benefit from easy access to the background material
provided in the TSD because the wildlife criteria are so new.  EPA, however, acknowledges
that the TSD repeats some of the material that appears in the Method.  EPA also is

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 concerned that the States, the Tribes and the public may become confused and mistakenly
 believe that the TSD also sets out binding requirements.  Consequently, EPA is considering
 either (1)  combining the TSD with the Method for publication in the CFR, or (2) publishing
 only the Method in the CFR and distributing the TSD widely.  EPA invites comment on this
 issue.  If option (1) is pursued, EPA invites comments on whether there are any components
 of the TSD which should not become binding requirements.

       As with the human health methodology, the wildlife methodology has both a hazard
 and an exposure component.  The hazard component is determined from the toxicity data for
 a given pollutant and the exposure component is determined from species-specific exposure
 parameters.

       a.  Parameters of the Hazard Component of the GLWQI Wildlife Criteria
 Methodology.  The Committees of the Initiative discussed various aspects of the hazard
 component of the final wildlife criteria methodology.  EPA is proposing to adopt the ideas
 they developed on several aspects of the hazard component of the wildlife method which are
 presented below.

       i.  LOAEL to NOAEL Extrapolations. In some studies when a range of doses are
 used, an effect is observed at the lowest chemical concentration used in the study.  The
 proposed Guidance proposes to allow use of an uncertainty factor that would permit a
 NOAEL to be estimated from the LOAEL determined in such a study. Experimental support
 for this concept is referenced in the Technical Support Document for Wildlife Criteria (the
 appendix to this preamble), as  well as appendix A to the Great Lakes Water Quality Initiative
 (GLWQI) Technical Support Document for Human Health Criteria and Values, which  is
 available in the administrative record  for this rulemaking.  Copies are also available upon
 written request to the address listed in section Xffl of this preamble.  EPA notes that use of
 such an adjustment factor is permitted within the existing human health water quality criteria
process (45 FR 79353-79354, November 28, 1980; and 50 FR 46944-46946, November, 13,
 1985).  EPA is proposing to allow this adjusted NOAEL value to be used in the derivation of
both Tier I wildlife criteria and Tier n wildlife values. EPA requests comment on  this
approach.

       ii.  Subchronic to Chronic Extrapolations.  The wildlife criteria methodology allows
for application of an uncertainty factor to adjust the NOAEL from a subchronic study to
estimate a chronic NOAEL.  Because of toxicokinetic considerations, bioassays that are of
insufficient duration to encompass a .significant portion of an organism's life span or a
sensitive life stage may underestimate hazards.  EPA proposes providing the option of
considering exposure length by extrapolating from subchronic studies to estimate chronic
impacts.  As presented in the Technical Support Document for Wildlife Criteria (the
appendix to this preamble), the value  of this term must be based on the bioaccumulative
potential of the chemical, toxicokinetic considerations, test length and available test data.
The value applied can range from 1.0 to 10, adopting the 10-fold uncertainty factor value
applied in the derivation of human health criteria as the upper limit for the value.
Endorsement of this approach by EPA is referenced in the Technical Support Document for
Wildlife Criteria (the appendix to this preamble), and experimental support for this  approach

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is referenced in appendix A to the GLWQI Technical Support Document for Human Health
Criteria and Values.  EPA requests comments on the provisions to allow for such
adjustments to the NOAEL in the derivation of wildlife criteria.

       iii.  Species Sensitivity Factor.  In the derivation of noncancer human health criteria,
an uncertainty factor is applied when extrapolating from results of long-term studies on
experimental animals to humans. EPA is proposing to allow use of a species sensitivity
factor (SSF) which adjusts for the same type of uncertainty-differences in lexicological
sensitivity—among wildlife species.  Specifically, it adjusts only for differences in
lexicological sensitivity between the test species (the species from which the NOAEL is
derived) and the representative wildlife species identified for protection or the species
identified as requiring greater protection.  (The SSF is  not intended to adjust for differences
with regard to body weight and food and water consumption rates between the test species
and representative species or the species requiring greater protection.)

       Guidance in the selection of a SSF value is provided in appendix D to part 132 and
the Technical Support Document for Wildlife Criteria.  The discussion of an interspecies
uncertainty factor located in section  C  of appendix A to the GLWQI Technical Support
Document for Human Health Criteria and Values may also be useful in determining the value
of a  SSF.

       In its December 16, 1992, report, "Evaluation of the Guidance for the Great Lakes
Water Quality Initiative," (U.S. EPA,  1992), EPA's Science Advisory Board (SAB)
recommended that the methodology for deriving wildlife criteria incorporate procedures mat
address a measure of the variability of species sensitivities observed in substance-specific
studies. The guidance provided in the Technical Support Document for Wildlife Criteria for
determining an appropriate SSF has  been revised following submission to the SAB for
review. The current guidance attempts to address the SAB's concerns and requires
consideration of the amount and quality of available studies; the diversity of species for
which data is available; known physicochemical, toxicokinetic and loxicodynamic properties
of the chemical; and similar data for chemicals thai operate by the same mode of action.
EPA requests comment on the guidance provided in determining the value of a SSF.

       For Tier I criteria, the Agency proposes thai the SSF may  be used to extrapolate
toxicity data across species within each of the  two taxonomic classes of Aves and Mammalia.
An interclass SSF may be used for a given chemical  for a Tier I criteria only if it can be
supported by a validated biologically-based dose-response model or by an analysis of
interclass lexicological data, incorporating the endpoints in question, for a chemical analog
that acts under the same mode  of toxic action.

       Participants at the Workshop discussed the range of values for SSFs. The Workshop
concluded that, in nearly all cases, the available lexicological dala for the determination of a
SSF  to be applied in the derivation of  a Tier I criteria, or any value calculated using the Tier
I approach, would result in a SSF within the range of 1.0 to 0.01. EPA is proposing to
require that a SSF outside of this range for a Tier I criteria, or any value calculated using the
Tier  I approach, must be based on sound scientific and technical reasons and must be

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 accompanied by a written justification presenting this reasoning. This justification should be
 provided to EPA by inclusion in the State's or Tribe's submission under § 132.5 of this
 proposed rule.  Use of a SSF outside of this range is prohibited unless approved by EPA
 based on its consideration of the justification provided.

       For Tier n wildlife values, EPA proposes that the SSF may be used to extrapolate
 toxicity data across the two taxonomic classes without the strict requirements presented above
 for use in deriving Tier I criteria. Because of the uncertainties associated with performing
 interclass extrapolations, and because Tier n values are intended to be conservative to
 encourage data generation, the SSF applied may not be greater than 1.0 but may be lower
 than 0.01.  A written justification is not required when a SSF less than 0.01 is used in the
 derivation of Tier n values.

       iv. Intraspecies Variability.  Procedure 1 in appendix F to this Guidance discusses
 site-specific modifications to criteria/values and suggests the use of an additional uncertainty
 factor in the equation used to calculate Wildlife Values.  Section Vm.A of this preamble
 presents a method for the use of this additional uncertainty factor, called an intraspecies
 uncertainty factor (ISF), to adjust for intraspecies variability in the development of site-
 specific criteria. The use of mis additional uncertainty factor provides an additional level of
 protection when protection of all individuals in a given population is desired.   The method
 presented in section VELA of this preamble proposes incorporation of an intraspecies
 sensitivity factor (ISF) into the hazard portion of the wildlife value equation.  The following
 discussion provides more detail on the ISF proposed in appendix F and section Vffl.A of this
 preamble.

       The ISF  is an uncertainty factor to adjust for intraspecies lexicological differences to
 protect sensitive individuals in a population. The National Academy of Sciences endorses the
 use of a 10-fold factor to account for differential sensitivities within the human population
 (NAS, 1980). A discussion of the experimental support for the application of an intraspecies
 uncertainty factor is provided in appendix A to the GLWQI Technical Support Document for
 Human Health Criteria and Values.  Although chronic toxicological data for wildlife species
 are relatively scarce, EPA believes that the factor of 10 that EPA has  developed to protect
 sensitive members of the human population will also protect sensitive  members of wildlife
 species.  EPA is proposing to allow, the use of an ISF value of 10 without requiring the
 development of  specific  justification.  EPA is proposing to require users who wish to use
 factors greater than 10 to develop specific and detailed scientific rationale for the factors they
propose to use.  The rationale must be submitted to EPA on request.  EPA anticipates that
 users who have  actual toxicological data from  wildlife studies may be  able to justify the use
of greater ISFs.  EPA is not proposing to permit the use of ISFs for wildlife that are less
than 10.

       In the December, 1992 Science Advisory Board (SAB) report (U.S. EPA, 1992), the
EPA's SAB identified the need for wildlife criteria to be constructed so that, in special cases,
they are able to  protect the individual rather than the population. EPA believes incorporation
of the ISF into the wildlife criteria methodology, as proposed in section Vm.A. of this
preamble, adequately addresses this concern. EPA invites comment on the ISF.

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       v.  Alternative Formula for Hazard Component of Equation.  In appendix D to part
 132, the hazard component is represented by:

                                  [NOAEL x SSF].

       The NOAEL applied in the equation may be: a NOAEL determined by applying a
LOAEL to NOAEL uncertainty factor to a LOAEL; or a NOAEL adjusted to account for
subchronic to chronic exposure durations by application of a subchronic to chronic
uncertainty factor.  In the equation, the NOAEL may be further adjusted to account for
interspecies toxicological differences multiplication by of a SSF and/or intraspecies
lexicological differences by division by an ISF. Because of these potential adjustments to the
NOAEL which may be carried out in the calculation of a wildlife value, in this preamble
EPA proposes a modification to the hazard component of the wildlife criteria calculation
equation presented in appendix D to part 132.  Rather than using the equation presented in
appendix D to part 132, EPA requests comment on the replacement of the hazard portion of
the equation (presented  at the beginning of this section) with the formula presented below:

                                         ED
                             UFS x UFC x  UF£  x UF,

       Where:
       ED = the Effect Dose in mg/kg-d for the test species.  This could be either a
NOAEL or a LOAEL.

       UFS = Uncertainty Factor for extrapolating toxicity data across species. Because it
appears in the denominator, the value of this term would be the inverse of the SSF described
and defined in appendix D to part 132 and the appendix to this preamble.

       UFC = Uncertainty Factor for subchronic to chronic exposures.  The value of this
term would be the subchronic to chronic uncertainty factor previously described and
discussed in appendix D to part 132 and the appendix to this preamble.

       UFE = Uncertainty Factor for LOAEL to NOAEL extrapolations.  The value of this
term would be the LOAEL to NOAEL uncertainty factor discussed in appendix D to part 132
and the appendix to this preamble.
           = Uncertainty Factor for intraspecies toxicological differences to protect
sensitive individuals in a population. Because it appears in the denominator above, this term
would be the inverse of the ISF proposed in section VELA of this preamble, and discussed
above in this section of the preamble.

      In many cases, the value for these uncertainty factors may be one. That is, values
other than 1.0 would rarely if ever be used for all uncertainty factors simultaneously.
However, EPA believes that the alternative formula has the advantage that it more clearly
presents the uncertainty factors employed. The equation used to derive wildlife criteria and
values would be:

                                          8

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                       wv
                            x  Wt
UFS x  UFC  x  UFE x UF,        A
        WA t- (FA  x BAF)
        The terms are defined above and in appendix D to part 132.  This formula appears
 more similar to that used in the derivation of noncancer human health criteria.  EPA requests
 comment on the adoption of the alternative formula in the final Guidance.

        b.  Parameters of the Exposure Component of the GLWQI Wildlife Criteria
 Methodology.  In deriving human health criteria, the exposure estimates employed are for
 one species, Homo sapiens.  The Committees of the Initiative and EPA, however, wanted to
 develop a wildlife method that would protect a broad range of wildlife species.  There are
 two possible ways to accomplish this: estimate exposure parameters for a hypothetical
 "model animal," (the approach  implicit in the Wisconsin methodology); or select an actual
 wildlife species as a representative wildlife species.  The Committees and EPA agreed to
 select representative species for the two taxonomic classes, Aves and Mammalia, in order to
 provide a basis for determining an appropriate SSF and incorporating empirical  exposure
 parameters where available for  specific species in each taxonomic class.  Selection of
 representative species which are then used to derive criteria to protect wildlife is a significant
 issue.  The criterion and selection process used to select the representative species is
 presented in section V of the Technical Support Document for Wildlife Criteria  (the appendix
 to this preamble). The species  selected are representative of Great Lakes basin  wildlife
 which are likely to experience significant exposure to contaminants from aquatic food webs.
 EPA requests comment on the selection process and the results employed in the  derivation of
 wildlife criteria.

       i. Approach Used to Select Representative Species Identified for Protection.  To
 select representative avian and mammalian species, an analysis of wildlife species that inhabit
 the Great Lakes basin was undertaken to identify those most likely to be exposed to
 environmental contaminants from aquatic  ecosystems (these representative species are not
 necessarily the most lexicologically sensitive species).  This analysis is presented in the
 Technical Support Document for Wildlife Criteria.  With regard to mammalian species,
 results of this assessment suggested  that, in  general, piscivorous species are at greatest risk
 from the chemicals identified for wildlife  criteria development (see section iii, below). Two
 mammalian  species were chosen to represent the range of body weights and food habits of
piscivorous mammals.  Representative avian species were categorized based on three species-
 specific parameters; body weight,  food habits (e.g., food source and prey size) and foraging
 styles.  Based on available data, the results of this assessment suggested that, with the
precision of available data, ingestion rates for birds were generally proportional  to animal
mass and not influenced by foraging style. Therefore, EPA is proposing to select
representative avian and mammalian species which represent a range of body weights and
food habits appropriate for the Great Lakes basin and which are likely to experience
significant exposure from the aquatic food web.

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       EPA requests submission of peer-reviewed empirical exposure information for wildlife
species residing in the Great Lakes basin which were not referenced in the analysis presented
in the Technical Support Document for Wildlife Criteria and which the commenter  feels
should be considered in the selection of representative avian and mammalian species.

       As a result of applying this approach, the representative species proposed to represent
avian and mammalian species of the Great Lakes basin which are likely to experience
significant exposure to contaminants in aquatic ecosystems through the food chain are the
mink (Mustela visori) and river otter  (Lutra canadensis) and the belted kingfisher (Ceryle
alcyon), osprey  (Pandion haliatus) and bald eagle (Haliaeetus leucocephalus).  EPA
specifically invites comment on the choice of representative species identified for protection,
and requests that the public document the basis for considering other species.

       The SAB, in their December 1992 report (U.S. EPA, 1992), recommended that the
approach to protect wildlife be expanded  to consider ecologically representative species.
EPA acknowledges that the approach used to select representative species does not consider
potential impacts on wildlife species due to changes in communities or the ecosystems in
which they reside and recognizes the need for research to better understand the large
uncertainties which currently exist in this area.  EPA welcomes suggestions on how to select
ecologically representative  species  given the current state of knowledge.

       ii.  Bioaccumulation Factors.  The procedure for determining the appropriate
bioaccumulation factor (BAF) for calculation of Tier I wildlife criteria and Tier n wildlife
values is presented in appendix B to part  132.  Based on the food habits of the representative
wildlife species, BAFs calculated for trophic levels 3 or 4 may be used.  BAFs for
invertebrates, aquatic plants or other trophic levels may also be used on a case-by-case basis
based on their proportion in the total diet consumed by the wildlife species requiring greater
protection.

       iii.  Exposure Routes Considered.  The derivation of the equation used to calculate
wildlife values, which are in turn used to calculate a wildlife criterion, considers oral
exposure (i.e. food and water ingestion).  EPA considers oral ingestion the most significant
route of exposure for bioaccumulative pollutants and these pollutants represent the greatest
risk to wildlife species.  EPA requests comments on this assumption.

       In its December 16, 1992 report,  "Evaluation of the Guidance for the Great  Lakes
Water Quality Initiative" (U.S. EPA, 1992), EPA's SAB expressed concern that the wildlife
exposure assessments in the proposed guidance do not consider exposures via inhalation or
dermal contact which may  be important for chemicals with significant vapor pressure and
intermediate molecular weights.  EPA solicits modifications of the proposed approach which
would address these concerns and consider  other significant routes of exposure for non-
bioaccumulative chemicals.
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 C. Additional Issues

       The sections below highlight some of the issues and discussions which occurred
 during the development of the wildlife criteria methodology proposed.  EPA solicits
 comments on each of these issues.

 1.  Use of Human Health Paradigm

       The December, 1992, SAB report (U.S.  EPA, 1992) states that the wildlife criteria
 concepts were formulated around the perceived requirements of the human health paradigm
 and they are inadequate for wildlife.  Adjustments made to the human health paradigm
 include: (1) defining database requirements such as preferred test species, test length, and
 toxicological endpoints; (2) selection  of species representative of wildlife species likely to
 experience significant exposure from aquatic food webs and for which empirical dietary
 exposure information was available; and (3) options for the use of various uncertainty factors
 to ensure protection of the distribution of wildlife species.  Given the extent of current
 exposure and toxicological data available for wildlife species, EPA believes the methodology
 (presented in appendix D to part 132, and clarified in the appendix to this preamble and the
 criteria derived based on this methodology, are scientifically defensible. EPA requests
 comments on additional modifications to the proposed methodology which would improve its
 scientific defensibility.

 2.  Minimum Database for Wildlife Criteria Derivation

       There was a considerable amount of discussion in the Committees of the Initiative and
 at the Workshop on the minimum toxicological database requirements for both Tier I criteria
 and Tier n values.  Due to the uncertainties in extrapolating data across taxonomic classes,
 EPA is proposing to require that the minimum toxicity database for Tier I criteria must
 provide enough data to generate a subchronic or chronic dose-response  curve for both birds
 and mammals.  For Tier n values, the minimum toxicity database need only provide enough
 data to generate a subchronic or chronic dose-response curve for one taxonomic class (Aves
 or Mammalia). In all cases, any study used in the derivation of wildlife criteria or values
 should be peer-reviewed.

       Additionally, if available, field studies of wildlife species shall take precedence over
 studies using traditional laboratory species in the development of wildlife criteria and values
because uncertainties in extrapolating from laboratory to field impacts are reduced.  Any
laboratory studies used must use avian or mammalian species.

       The oral exposure route is the primary route of exposure to be considered in selecting
toxicity studies.  EPA proposes that studies involving other exposure routes (e.g., dermal or
inhalation) should be considered in the derivation of a Tier I criteria or Tier n value only
when an equivalent oral dose can be estimated.  Such an estimation should be supported by
toxicokinetic and in vivo metabolism  data. Without this supporting data, the mechanism of
toxicity and/or the dosimetry for these routes of exposure cannot be assumed to be the same
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as for the oral route of exposure, and the criteria and value calculations are based on an oral
route of exposure.

       If laboratory studies are used to derive a Tier I criteria, EPA is proposing a 90-day
requirement for any mammalian study and a 28-day requirement for any avian study. This is
to ensure that the toxicity data on which a wildlife criterion is based does not underestimate
effects associated with repeated exposures to a chemical.

       If laboratory studies are used to derive a Tier n value, EPA is proposing the same
requirements for Tier I except a 28-day mammalian study which meets the other
requirements presented in appendix to part 132 may also be used.

3. Acceptable Endpoints for Toxicity Studies

        The acceptable endpoints on which the NOAEL determined from the toxicity study
must be based are defined in the wildlife methodology presented in appendix D to part 132.
These endpoints were selected because they are parameters most likely to influence
population dynamics.  When more than one study is available which assessed different
endpoints, EPA recommends that preference be given to studies which assess endpoints
which best reflect potential impacts to wildlife populations.

       EPA's SAB, in their  December  16, 1992 report (U.S. EPA, 1992), recommended that
EPA develop guidance for the selection of NOAELs appropriate for the protection of wildlife
populations as distinct from  the protection of individuals.  EPA proposes that the restrictions
and clarifications provided in the methodology adequately address this concern given the
current  extent of knowledge  regarding population dynamics.  EPA requests comments on
other  approaches which may address the recommendation received from EPA's SAB.

4. Use of an Acute to Chronic Conversion Ratio

       Participants at  the Workshop and the Committees of the Initiative discussed the
application of acute to chronic conversion ratios in the derivation of Tier I criteria. An
acute/chronic ratio is applied to acute toxicity data (typically mortality) to estimate chronic
effect levels. Workshop participants concluded that more data analysis of existing
mammalian and avian acute  and chronic toxicity data, possibly broken down by class of
compound or mode of action, was needed to adequately define the empirical relationship
between acute endpoints (e.g., LD50, the lethal dosage causing death in 50 percent of die
exposed animals) and  chronic endpoints (e.g., NOAEL, the highest tested dosage causing no
observed adverse effect). Workshop participants recognized that before the use of
acute/chronic ratios could be scientifically defensible, additional toxicity data might be
needed. Given the current limited database, there was concern that the factor for
extrapolating from acute data to chronic data would have to be so large that it would result in
criteria  or values which could be overly conservative.  Therefore, EPA is proposing not  to
incorporate the use of an acute-to-chronic conversion factor in the Tier I methodology.  EPA
is also proposing that  Tier n values not be based solely on acute toxicity data,  instead
                                          12

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 requiring the use of subchronic or chronic data to derive an effect value. EPA invites
 comments on these proposed decisions.

 D.  Chemical Selection for Wildlife Criteria Derivation

       The types of chemicals for which wildlife criteria should be developed under the
 GLWQI were addressed by the Workshop. These are: those which bioaccumulate (because
 wildlife species occupy higher levels in the trophic structure of a food web and, therefore,
 have a higher exposure); and those which have a unique metabolic pathway or mode of
 action which may make birds or mammals more sensitive lexicologically.  The Committees
 of the Initiative agreed with the proposals of the Workshop that chemicals BAF greater than
 250 should receive  top priority for derivation of wildlife criteria.  In addition, chemicals
 with BAFs less than 250 where wildlife impacts are suspected (e.g., lead) were included in
 the top priority list.

       The Initiative Committees also identified non-persistent, multiple application biocides
 (such as triazine herbicides and carbamates) are another group of chemicals for which
 wildlife criteria may be derived.  These chemicals, although they  are highly degradable and,
 therefore, have low bioaccumulation factors, are known to have detrimental effects on
 wildlife.

       EPA agrees  that the chemicals described above are those that most warrant the
 development of wildlife criteria and values.  EPA is not requiring the Great Lakes States or
 Tribes to develop values for all of these chemicals, nor is EPA prohibiting any State or Tribe
 from addressing other chemicals if it believes that those other chemicals are causing  adverse
 impacts on wildlife. EPA merely recommends that States or Tribes place a high priority on
 developing wildlife values for the chemicals identified by the Committees. EPA also intends
 to focus any future  efforts to develop additional Tier I criteria for wildlife on these same
 chemicals of concern.

 E.  Tier I Wildlife Criteria and Tier II Wildlife Values

       In the proposed Guidance, there are four chemicals for which Tier I wildlife  criteria
 are proposed.  These are mercury, PCBs, 2,3,7,8-TCDD, and DDT and metabolites. Only
 four wildlife criteria are being proposed for two major reasons: field studies from the Great
 Lakes indicate that  the four pollutants for which wildlife criteria are proposed have had the
 most severe impacts on wildlife within the Great Lakes; and the criteria proposed are the
 first set of criteria for wildlife that EPA has ever developed.  EPA cannot take advantage of
 an established and peer-reviewed National  methodology to develop National wildlife  criteria
 as it can  for both human health and aquatic life criteria. The Initiative  Committees and EPA
 lacked time and resources to develop additional numeric criteria for wildlife prior to  this
proposal.  The  State of Wisconsin had already identified these four chemicals as chemicals of
 concern for wildlife impacts in their State and completed literature reviews for these  four
chemicals.  These literature reviews were updated as part of the GLWQI effort. The
proposed numerical criteria are presented in Table VI-1.  For additional information, EPA
refers readers to the proposed methodology in appendix D to part 132,  the Technical Support

                                          13

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Document located in the appendix to this preamble, and the individual criteria documents
available in the 2 administrative record for this rulemaking.  No Tier n wildlife values were
calculated for inclusion in the proposed Guidance.

Table VI-1.   Great Lakes Tier I Wildlife Criteria
Chemical                                            Criteria (pg/L)

p,p'-dichlorodiphenyltrichloroetnane
      (DDT) and Metabolites                          0.87

Mercury (including Methylmercury)                    180

Polychlorinated biphenyls (PCBs)                      17

2,3,7,8-tetrachlorodibenzo-p-dioxin
      (2,3,7,8-TCDD)                                0.0096
F.  Comparison With the CWA and Relationship to National Guidance

      The observed effects on wildlife species in the Great Lakes basin are clear evidence
that the Clean Water Act (CWA) goals of protecting the biological integrity of the Nation's
waters and attaining water quality which provides for the protection of wildlife are not being
met in the Great Lakes (see 33 U.S.C. 1251(a)).

1.  Relationship to Existing National Guidance

      Currently, there exists no National guidance for wildlife protection comparable to the
proposed Guidance. However,  there is a mechanism for consideration of wildlife impacts
within the 1985 National aquatic life criteria guidelines (Stephan, et. ah, 1985).  In those
guidelines, if a maximum permissible tissue concentration is available from a maximum
acceptable dietary intake based on observations on survival, growth, or reproduction in: a
chronic wildlife feeding study; or a long-term wildlife field study, or from an  FDA Action
Level, a Final Residue Value can be calculated. This Final Residue Value is calculated by
dividing maximum permissible tissue concentrations by appropriate lipid-normalized
bioconcentration or bioaccumulation factors.

      This methodology provides a mechanism to protect against bioaccumulation of a
compound within a food web.  However, it also has limitations.  A Final Residue Value
derived using an FDA Action Level does not ensure protection of wildlife species which may
consume contaminated aquatic organisms as a larger portion of their diet or exhibit a

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 greater sensitivity than the human which the FDA Action Level is derived to protect.  If no
 maximum permissible tissue concentration is available, no Final Residue Value is calculated
 and, therefore, biomagnification of a chemical into the higher trophic levels of a food web,
 and potential impacts on these wildlife species, is not considered in the derivation of the
 Aquatic Life Criterion.

       EPA's current National aquatic life criteria for DDT and PCBs are based on wildlife
 toxicity information (U.S. EPA, 1980a and b, respectively).  Wildlife toxicity data was also
 considered in the derivation of the current aquatic life criterion for mercury (U.S. EPA,
 1984).  For both DDT and PCBs, a bioconcentration factor (BCF) rather than a
 bioaccumulation factor was used in the derivation of these aquatic life criteria.  In both
 cases,  the BCF was known to underestimate the bioaccumulative potential of the compound,
 and in the PCB Aquatic Life Criteria document (U.S. EPA,  1980c), underestimating the
 bioaccumulative potential was identified as leading to a criterion  which  may be
 underprotective of wildlife species at risk.

       EPA has begun a separate effort to derive National wildlife criteria. Following the
 release of the 1987 General Accounting Office report entitled "National Refuge
 Contamination is Difficult to Confirm and Clean  Up," (GAO, 1987), EPA began to work
 cooperatively with U.S. Fish and Wildlife Service to develop methods for deriving National
 wildlife criteria. The wildlife criteria efforts carried out within the Great Lakes Water
 Quality Initiative have been coordinated with the on-going National efforts.  However, within
 the development of National wildlife criteria, wildlife are defined as mammals, birds, reptiles
 and amphibians. This broader definition of wildlife was considered in the early stages of
 wildlife criteria development for the GLWQI.  However, the decision was made to move
 forward with wildlife criteria considerate of impacts on mammals and birds at this time
 because of the lack of chronic or sub-chronic lexicological data for reptiles and amphibians.
 The incorporation of effects on reptiles and amphibians is also complicated by the
 significance of, and lack of data for, the dermal route of exposure to reptiles and amphibians.
 EPA requests recommendations on how reptiles and amphibians can be  incorporated into the
 proposed GLWQI methodology or suggestions for an alternative wildlife criteria methodology
 considerate of impacts on reptiles and amphibians.

 2.  Relationship to Current Efforts to Provide National Guidance for the Development of
 Wildlife Criteria

       There are efforts underway within EPA to develop guidance for National wildlife
 criteria.  The proposed Guidance is being considered as one  alternative  which might be
 modified for nationwide use. The Great Lakes Guidance has as its focus the protection of
wildlife populations inhabiting the Great Lakes basin. Although National guidance may
eventually be modeled on the proposed Guidance, it should not be expected that the National
guidance would result in identical criteria. EPA  invites comments on the modification of this
approach for development of a National wildlife criteria procedure.
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G.  Comparison of Wildlife Criteria and Methods to National Program and to Great Lakes
Water Quality Agreement

1.  "No Less Restrictive" than the CWA and National Guidance

       Since the current National guidance contains no method for calculating criteria for the
sole protection of wildlife and no values based solely on the protection of wildlife, a direct
comparison is difficult. The National guidance allows some consideration of wildlife impacts
in the calculation of criteria for aquatic life.  Current National criteria for aquatic life can be
compared with the  proposed criteria for wildlife, although the comparison may not be
especially meaningful. All four of the Tier I criteria for wildlife proposed are, in fact, more
restrictive than the  existing aquatic life  standards for the same pollutants. Since the new
wildlife criteria will apply in almost all Great Lakes waters, they will in a rough sense
provide more protection than the National guidance.

      As explained in section B above, in the discussion of aquatic life criteria, Tier n
values will almost always be more restrictive than both new Great Lakes Tier I criteria and
existing National criteria. Hence, EPA believes that future Tier n wildlife values generally
will not be less restrictive than the National program.

2.  Conformance with the Great Lakes Water Quality Agreement

       As explained above in the discussion of aquatic life criteria, EPA does not believe
that Congress intended to require EPA to adopt criteria identical to the specific numerical
limits set out as "Specific Objectives" in Annex 1 of the Great Lakes Water Quality
Agreement (GLWQA). In addition, only five of these "Objectives" focus on the protection
of wildlife.   EPA notes that the proposed wildlife criterion that can be most readily compared
to a wildlife limit in the GLWQA is more restrictive than the GLWQA's limit.  EPA is
proposing a wildlife criteria for DDT of 0.87 pg/L. The GLWQA's Annex 1 limit for DDT
is 3.0 pg/L.

      Finally, as discussed above, EPA intends to try to revise the GLWQA to replace
existing Annex  1 limits with the new criteria proposed.

H.    Bibliography

Great Lakes Water Quality Criteria Initiative. Appendix A:  Uncertainty Factors in   Great
      Lakes Water Quality Criteria Initiative Technical Support Document for Human Health
      Criteria and  Values. NTIS #PB93-15468.  ERIC: 3940.

National Academy  of Sciences.   1980.  Problems of Risk Estimation,  pp. 25-65 in Drinking
      Water and Health, Volume 3.  National Academy Press, 2101 Constitution Avenue,
      NW, Washington, D.C.  20418.
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 Stephan, C.E., D. I. Mount, D. J. Hansen, J.H. Gentile, G.A. Chapman, and W.A. Brungs.
       1985.  Guidelines for deriving numerical national Water Quality Criteria for the
       Protection of Aquatic Organisms and their uses.  PB85-227049. National Technical
       Information Service. Springfield, VA.

 U.S. EPA.  1980a. Ambient Water Quality Criteria for DDT. Office of Water Regulations
       and Standards, Criteria and Standards Division.  U.S. EPA. Washington, D.C.  EPA
       440/5-80-038.

 U.S. EPA.  1984. Ambient Water Quality Criteria for Mercury. Office of Water
       Regulations and Standards, Criteria and Standards Division.  U.S. EPA.  Washington,
       D.C.  EPA 440/5-80-058.

 U.S. EPA.  1980b. Ambient Water Quality Criteria for Polychlorinated Biphenyls.  Office
       of Water Regulations and Standards, Criteria and Standards Division. U.S. EPA.
       Washington, D.C. EPA 440/5-80-068.

 U.S. EPA.  1980c. Appendix C.  Guidelines and Methodology Used in the Preparation of
       Health Effect Assessment Chapters of the Consent Decree Water Criteria Documents.
       pp. 79347-79357 in Water Quality Criteria Documents;  Availability.  Federal
       Register. 45:79318-79378. Friday, November 28, 1980.

 U.S. EPA.  1992. An SAB Report: Evaluation of the Guidance for the Great Lakes Water
       Quality Initiative.  Science Advisory Board,  U.S. EPA,  Washington, D.C.  EPA-SAB-
      EPEC/DWC-93-005.

 U.S. EPA.  1985. Section V.C. Evaluation of Health Effects and Determination of RMCLs
      pp. 46944-46950 in National Primary Drinking Water Regulations; Synthetic Organic
      Chemicals; Inorganic Chemicals and Microorganisms. 50 FR 46936-47022.
      Wednesday, November 13, 1985.

 U.S. General Accounting Office. 1987.  Wildlife Management National Refuge
      Contamination is Difficult to Confirm and Clean  Up.  Gaithersburg, MD.
      GAO/RCED-87-128.

Wisconsin Administrative Code, Chapter NR 105.  Surface Water Quality Criteria for Toxic
      Substances. Register, February, 1989, No. 398.

Technical Support Document for Chapter NR 105 of the Wisconsin Administrative Code.
      May  1988.
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 CHAPTER 2
      Appendix D to Part 132~Great Lakes  Water Quality
 Initiative Methodology for the Development  of Wildlife
 Criteria  and Values

 I. Introduction

      A Great Lakes Water Quality Wildlife Criterion (GLWC) is the concentration of a
 substance which, if not exceeded, protects avian and mammalian wildlife populations
 inhabiting the Great Lakes basin from adverse effects resulting from the ingestion of surface
 waters and aquatic prey taken from surface waters of the Great Lakes System.  These criteria
 are numeric  or narrative in nature and are based on existing lexicological studies of the
 substance of concern and quantitative information about the exposure of wildlife species to
 the substance (i.e., food and water consumption rates).  Since lexicological and exposure
 data for individual wildlife species is limited, a GLWC is derived using a methodology
 similar to that used to derive noncancer human health criteria (Barnes and Dourson, 1988;
 NAS, 1977;  NAS, 1980; U.S. EPA. 1980). Separate avian and mammalian values are
 developed using taxonomic class-specific toxicity data and exposure data for five
 representative Great Lakes basin wildlife species.  The representative wildlife species
 selected are representative of avian and  mammalian species resident in the Great Lakes basin
 which are likely to experience significant exposure to contaminants through the aquatic food
 web; they are die bald eagle, osprey, belted kingfisher, mink, and river otter.  Taxonomic
 class-specific avian and mammalian Wildlife Values (WVs)-concentrations of a substance
 which if not  exceeded should protect the wildlife species—are calculated using the geometric
 means of the species' WVs and the lower of the mammalian and avian WVs is selected as
 the GLWC.

      This appendix establishes a two-tiered approach to the protection of avian and
 mammalian communities in the Great Lakes basin.  This appendix sets forth the method for
 deriving both Tier I criteria and Tier n  values.

 n.  Calculation of Wildlife Values for Tier 1 Criteria and Tier II Value Development

      Table  4 of part 132 and Table D-l of this appendix to part 132 contain the proposed
 Tier I criteria calculated by EPA pursuant to the provisions below.  No Tier n values have
been calculated.

 A.  Equation for Avian Mammalian Wildlife Values

      The Tier I GLWC is the lower of the two taxonomic class-specific wildlife values.  A
Tier n value may be based on the wildlife value derived from a  single taxonomic class.
These wildlife values are calculated using the equation presented below.
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       WV =fNQAEL X SSF1 x Wt.
            WA + [FA  x BAF]

       Where:
       WV =  Wildlife value in milligrams of substance per liter (mg/L).

       NOAEL = No observed adverse effect level in milligrams of substance per kilogram
 of body weight per day (mg/kg-d) as derived from mammalian or avian studies as described
 in section n.E of this document.

       WtA =  Average weight in kilograms (kg) for the representative species identified for
 protection or the species identified as requiring greater protection.

       WA = Average daily volume of water consumed in liters per day (L/d) by the
 representative  species identified for protection or the species identified as requiring greater
 protection.

       SSF =  Species sensitivity factor. An extrapolation factor to account for differences in
 toxicity between species. Further information is provided in section ffl.I of this document.

       FA = Average daily amount of food consumed in kilograms per day (kg/d) by the
 representative  species identified for protection or the species identified as requiring greater
 protection.

       BAF = Aquatic life bioaccumulation factor for wildlife in liters per kilogram (L/kg).
 Chosen using guidelines for wildlife presented in appendix B to part  132, Methodology for
 Development of Bioaccumulation Factors.

       The term  "wildlife value" is used to denote any value which results from each
 application of the equation presented above or any averaging of such numbers.  It can refer
 to values derived using either the Tier I or Tier n database requirements.  Wildlife values
 calculated for the representative species are used to calculate taxonomic class-specific wildlife
 values. "Tier  n wildlife value," or  "Tier n value," is used  to denote any final number
 derived from data meeting only the Tier n requirements and using the procedure presented in
 this document.  "Tier I wildlife value," or Tier I value," is used to denote any final number
 derived from data meeting the Tier I database requirements calculated using the procedure
presented in this document.  "Tier I criteria" are the four wildlife criteria presented in Table
4 of part 132 and in Table D-l of this appendix to part 132.

B.  Identification of Representative Species for Protection

       Piscivorous species are identified as the focus of concern for wildlife criteria
 development in the Great Lakes. An analysis of known or estimated exposure components
for avian and mammalian wildlife species is presented in the Technical Support  Document
for Wildlife Criteria (U.S. EPA, 1993a).  This analysis identifies three avian species and two
mammalian species as representative species  for protection.  The NOAEL obtained from

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toxicity data for each taxonomic class is used to calculate Wildlife Values (WVs) for each of
the five representative species identified for protection.

    Because of the lack of empirical species-specific exposure information for all wildlife
species in each taxonomic class, the geometric means of wildlife values for the representative
species within each taxonomic class are used to determine the taxonomic class-specific
wildlife value.

C.  Identification of Species Requiring Greater Protection

       Identification  of Species Requiring Greater Protection.  If exposure and/or hazard data
identifies a Great Lakes basin avian or mammalian wildlife species which is at risk, for
which the wildlife criteria or Tier n value based on the representative species may not be
adequately protective, the final avian or mammalian WV will be calculated specifically for
that species. A class-specific WV for a species determined to require greater protection is
calculated using the equation presented above, but using exposure information for the species
determined to require greater protection.  Toxicity information specific for that species is
also used if it is available.  This provision can be invoked in the derivation of site-specific
criteria where a wildlife species has been determined to require greater protection.

D.  Calculation of Avian and Mammalian Wildlife Values

       The taxonomic class-specific Wildlife Values (WV) can be determined in two ways,
both of which use the equation presented above.  The avian WV is the geometric mean of the
WVs calculated for the three representative avian species identified for protection or it is the
WV calculated for an avian species determined to require greater protection. The
mammalian  WV is the geometric mean of the WVs calculated for the two representative
mammalian  species or it is the WV calculated for a mammalian species determined to require
greater protection.  When a WV is calculated for a species determined to require greater
protection, the taxonomic class-specific WV for use in the determination of a GLWC is the
lower of the WVs calculated  for the given taxonomic class (the geometric mean of the WVs
calculated for the representative species or the WV calculated for the species determined to
require greater protection.) The Tier I GLWC is set equivalent to the lower of the avian or
mammalian  WVs determined.

ffl. Parameters of the Hazard Component of the Criteria Methodology

A.  Definitions

       The following definitions provide additional specificity and guidance in the evaluation
of toxicity data and the application of this methodology. These definitions are applicable to
both Tier I criteria and Tier n value development.

      Acceptable endpoints.  For the purpose of wildlife criteria derivation, acceptable
subchronic and chronic endpoints are those which affect organismal growth or viability, or
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 reproductive or developmental success or any other endpoint which is, or is directly related
 to, parameters that influence population dynamics.

       Chronic effect.  An adverse effect, measured by assessing an acceptable endpoint,
 resulting from continual exposure over several generations, or at least over a significant part
 of the test species projected life span or life stage.

       Lowest-observed-adverse-effect-level (LOAEL). The lowest tested dose or
 concentration of a substance which resulted in an observed adverse effect in exposed test
 organisms when all higher doses or concentrations resulted in the same or more severe
 effects.

       No-observed-adverse-effect-level(NOAEL).  The highest tested dose or concentration of
 a substance which did not result in an observed adverse effect in exposed test organisms.

       Subchronic effect.  An adverse effect,  measured by assessing an acceptable endpoint,
 resulting from continual exposure for a period of time less than that deemed necessary for a
 chronic test.

 B. Minimum Toxicity Database  for Tier I Criteria Development

       A NOAEL or LOAEL value is required for criterion calculation. To derive a Tier I
 criterion for wildlife, the minimum toxicity database required must provide enough data to
 generate a subchronic  or chronic dose-response curve for any given substance for both
 mammalian and avian  species.

       In reviewing the toxicity data available which  meets the minimum data requirements
 for each taxonomic class, the following order of preference shall be applied  to select the
 appropriate NOAEL or LOAEL to be used for calculation of individual wildlife values.  Data
 from peer-reviewed field studies of wildlife species takes precedence over other types of
 studies.  An acceptable field study must be of subchronic or chronic duration, provide a
 defensible, chemical-specific dose-response curve in  which cause and effect are clearly
 established, and assess acceptable endpoints as defined in this document.  When acceptable
 wildlife field studies are not available, the needed toxicity information may come from peer-
 reviewed laboratory studies.  When laboratory studies are used, preference shall be given to
 laboratory  studies with wildlife species over traditional laboratory animals to reduce
 uncertainties in making interspecies extrapolations. Whenever possible, all available
 laboratory  data and field studies shall be  reviewed to corroborate the final GLWC, to  assess
 the reasonableness of the toxicity value used, and to  assess the appropriateness of any
 uncertainty factors which are applied.

       When laboratory data are used, the following  requirements must be met:

       1.  The mammalian data must come from at least one well-conducted  study of 90 days
or greater designed to observe subchronic or  chronic effects as defined in this document.
                                           21

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      2.  The avian data must come from at least one well-conducted study of 28 days or
greater designed to observe subchronic or chronic effects as defined in this document.

      In reviewing the studies from which a NOAEL is derived for use in calculating a
wildlife value, studies involving exposure routes other than oral may be considered only
when an equivalent oral daily dose can be estimated and technically justified.  This is
because the mechanism of toxicity and/or issues of dosimetry (e.g. delivered dose to target
organs,  extent of xenobiotic metabolism, etc.) for other routes of exposure (e.g., dermal  or
inhalation) may differ; and the criteria and value calculations are based on an oral route of
exposure.

      In assessing the studies which meet the minimum data requirements, preference should
be given to studies which assess effects on developmental or reproductive endpoints because,
in general, these are more important endpoints in ensuring that a population's productivity is
maintained.

C.  Minimum Toxicity Database for Tier n Wildlife Value Development

      For those substances for which Tier I criteria cannot be derived, all data from avian
and mammalian species may be considered in the development of Tier n values.  To derive a
Tier n value for wildlife, the minimum toxicity database required must provide enough data
to generate a subchronic or chronic dose-response curve for any given substance for either a
mammalian or avian species.  Subchronic or chronic toxicity data shall be  used to derive
NOAELs  for Tier n values. When laboratory data for avian species is used to calculate  a
Tier n wildlife value, it must meet the same requirements presented above for Tier I criteria
derivation. When laboratory data for mammals is used to calculate a Tier n wildlife value,  a
28-day subchronic study which assessed acceptable endpoints may be used in addition to
studies which meet  the requirements presented above for Tier I criteria derivation.  Relevant
LD50 or eight-day LC50 values from avian and mammalian studies may be used in support
of subchronic and chronic toxicity data; however, a Tier n value shall not be calculated
solely on the basis of LD50 or eight-day LC50 data.

D.  Selection of NOAEL or LOAEL Data

      In selecting data to be used in the derivation  of wildlife values, the nature of the
observed endpoints  will be the primary selection criterion.  All data not part of the selected
subset may be used to assess the reasonableness of the toxicity value and the appropriateness
of any uncertainty factor which is applied.

      1.  If more than one NOAEL is available within a taxonomic class,  based on different
endpoints  of toxicity, that NOAEL which likely best reflects potential impacts to wildlife
populations through resultant changes in mortality and/or fecundity rates shall be used for the
calculation of wildlife values.

      2.  If more than one NOAEL is available within a taxonomic class based on the same
endpoint of toxicity, the NOAEL  from the most sensitive species is used.

                                          22

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       3.  If more than one NOAEL based on the same endpoint of toxicity is available for a
 given species, the NOAEL for that species shall be calculated using the geometric mean of
 those NOAELs.

 E.   Determination of the NOAEL in Proper Units

       In those cases in which a NOAEL is available in units other than mg/kg-d, the
 following procedures shall be used to convert the NOAEL to appropriate units prior to
 calculating a wildlife value.

       If the NOAEL is given in milligrams of toxicant per liter of water consumed by the
 test animals (mg/L), the NOAEL shall be multiplied by the daily average volume of water
 consumed by the test animals in liters per day (L/d) and divided by the average weight of the
 test animals in kilograms (kg).

      If the NOAEL is given in milligrams of toxicant per kilogram of food consumed by
 the test animals (mg/kg), the NOAEL shall be multiplied by the average amount of food in
 kilograms consumed daily by the  test animals (kg/d) and divided by the average weight of the
 test animals in kilograms (kg).

 F. Drinking and Feeding Rates

      When drinking and feeding rates and body weight are needed to express the NOAEL
 in mg/kg-d, they should be obtained from the study from which the NOAEL  was derived. If
 not already determined, body weight, and drinking and feeding rates are to be converted to a
 wet weight basis.

      If the study does not provide the needed values, they shall be determined from
appropriate data tables for the particular study species. For studies done with domestic
laboratory animals, the following  reference should be consulted:  Registry of Toxic Effects
of Chemical Substances (National Institute for Occupational Safety and Health, the latest
edition, Cincinnati, OH.).  When  insufficient data exist for other mammalian  or avian
species, the allometric equations from Calder and Braun (1983) and Nagy (1987) which are
presented below shall be applied to approximate the needed feeding or drinking rates.

      For mammalian species the allometric equations are:
      1. FA =0.0687
      Where:
      FA = Feeding rate of mammalian species in kilograms per
      day (kg/d) dry weight.
      WtA  = Average weight in kilograms (kg) of the test
      animals.
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      2. WA=0.099 x (WtJ090
      Where:
      WA = Drinking rate of mammalian species in liters per day (L/d).
      WtA  = Average weight in kilograms (kg) of the test
      animals.

      For avian species the allometric equations are:
      3. FA=0.0582 (WtJ0-65
      Where:
      FA = Feeding rate of avian species in kilograms per day(kg/d) dry
      weight.
      WtA  = Average weight in kilograms (kg) of the test
      animals.

      4. WA=0.059 x (WtJ0-®7
      Where:
      WA = Drinking rate of avian species in liters per day  (L/d).
      WtA  = Average weight in kilograms (kg) of the test animals.

G.  LOAEL to NOAEL Extrapolations

      In those cases in which a NOAEL is unavailable and a LOAEL is available, the
LOAEL may be adjusted to estimate the NOAEL.  Typically, the LOAEL is divided by an
uncertainty  factor to estimate a NOAEL for use in deriving wildlife values.  The value of the
uncertainty  factor is typically within the range of 1.0 and  10, depending on the dose-response
curve.  Additional references which support this concept  and are useful in choosing an
appropriate LOAEL to NOAEL uncertainty factor are provided in the Technical Support
Document for Wildlife Criteria (U.S. EPA, 1993a). Assistance in choosing an appropriate
LOAEL to  NOAEL uncertainty factor is also provided in  appendix A to the Great Lakes
Water Quality Initiative (GLWQI) Technical Support Document for Human Health Criteria
and Values  (U.S. EPA, 1993b).

H.  Subchronic to Chronic Extrapolations

      In certain instances where only subchronic data are available, the NOAEL  may be
divided by an uncertainty factor to extrapolate from subchronic to chronic levels.  Typically
the value of the uncertainty factor is within the range of 1.0 and 10.  This factor may be
used when assessing highly bioaccumulative substances where toxicokinetic considerations
suggest that a bioassay of limited length underestimates chronic hazard.  Assistance in
choosing an appropriate subchronic to chronic uncertainty factor is provided in appendix A to
the GLWQI Technical Support Document for Human Health Criteria and Values (U.S. EPA,
1993b).
                                         24

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 I.  Species Sensitivity Factor

       The selection of the species sensitivity factor (SSF) shall be based on the available
 lexicological data and on available data concerning the physicochemical, toxicokinetic and
 toxicodynamic properties of the substance in question and the amount and quality of available
 data.  This value is an uncertainty factor that is intended to account for differences in
 lexicological sensitivity among species.  Guidance for choosing the SSF is provided in the
 Technical Support Document for Wildlife Criteria (U.S. EPA, 1993a).  The discussion of an
 interspecies uncertainty factor located in appendix A to the GLWQI Technical Support
 Document for Human Health Criteria and Values (U.S. EPA, 1993b) may also be useful in
 determining the appropriate value for a SSF.

       For the derivation of Tier I criteria, a SSF within the range of 0.01 to 1.0 may be
 applied. If a SSF outside this range is used, it must be based on sound scientific and
 technical reasons and must be accompanied by a written justification presenting this
 reasoning. This justification shall be provided to EPA as part of the State's or Tribe's
 submission as required under § 132.5. Use of a SSF outside this range is prohibited unless
 approved by EPA based on its consideration of the justification provided. For Tier I wildlife
 criteria, the SSF shall be used for extrapolating toxicity data across species within a
 taxonomic class. The Tier I SSF is not intended for interclass extrapolations because of the
 poorly defined comparative toxicokinetic and toxicodynamic parameters between  mammals
 and birds.  However, an interclass extrapolation employing a SSF may be used for a given
 chemical if it can be supported by a validated biologically-based dose-response model or by
 an analysis of interclass lexicological data, considerate of acceptable endpoints, for a
 chemical analog that acts under the same mode of toxic action.

       For the derivation of Tier n wildlife values, a SSF may not be greater than 1.0 but
 may be lower than 0.01 without requiring a written justification.  For Tier n wildlife values,
 the SSF may be used to extrapolate toxicity data across the two taxonomic classes.

 IV.  Parameters of the Exposure Component of the Wildlife Criteria Methodology

 A.  Drinking and Feeding Rates of Representative Species or Species Requiring Greater
 Protection.

       The body weights (WtJ, feeding rates (FJ, and drinking rates (WJ for each of the
 five representative species are presented in Table D-2 of this appendix.  Trophic  level dietary
 composition for  these species are also presented in Table D-2 of this appendix  for use in
 selecting the correct bioaccumulation factor for use in the WV equation.

       If the feeding rate (FJ or drinking rate (W^J  for the species requiring greater
protection are not known, they can be estimated using  the allometric equations presented
above in section ELF of this appendix.
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B.  Bioaccumulation Factors

      The Methodology for Development of Bioaccumulation Factors is presented in
appendix B to part 132. This Guidance document specifies that, in general, trophic level
three or four BAFs are to be used in the derivation of wildlife values, depending on the
species identified for protection.  Trophic level three and four BAFs are used because these
are the trophic levels at which the representative species identified for protection feed.
Options to use plant and or other trophic level BAFs are permitted based on the identification
of a species requiring greater protection which may feed, in part or whole, at other trophic
levels.

V.  References

Barnes D. G. and M. Dourson. 1988.  Reference Dose (RfD): Description and Use in
      Health Risk Assessments.  Regul. Toxicol. Pharmacol.  8:471-486.  Academic Press,
      Inc. 1250 6th Avenue, San Diego, CA 92101-4312.

Calder m, W. A. and E. J. Braun.  1983. Scaling of Osmotic Regulation in Mammals and
      Birds.  American Journal of Physiology. 244:601-606. Williams and Wilkins, 1316
      East 16th Street, Brooklyn, NY  11230-6003.

Nagy, K. A.  1987. Field Metabolic Rate and Food Requirement Scaling in  Mammals and
      Birds.  Ecological Monographs.  57(2): 111-128.  Ecological Society of America,
      Arizona State University, Tempe, AZ  85287-0001.

National Academy of Sciences.  1977.  Chemical Contaminants: Safety and Risk Assessment,
      pp. 19-62 in Drinking Water and Health, Volume 1. National Academy Press,  2101
      Constitution Avenue, NW, Washington, D.C.  20418.

National Academy of Sciences.  1980.  Problems of Risk Estimation, pp. 25-65 in Drinking
      Water and Health, Volume 3.  National Academy Press,  2101  Constitution Avenue,
      NW,  Washington,  D.C. 20418.

National Institute for Occupational Safety and Health. Latest edition. Registry of Toxic
      Effects of Chemical Substances (available only on microfiche or as an  electronic
      database). Division  of Standards Development and Technology Transfer, 4676
      Columbia Parkway, Cincinnati, OH 45226.

U.S. EPA.  1980. Appendix C.  Guidelines and Methodology Used in the Preparation of
      Health Effect Assessment Chapters of the Consent Decree Water Criteria Documents.
      pp. 79347-79357 in Water Quality Criteria Documents; Availability.  Available from
      U.S. Environmental Protection Agency, Office of Water Resource Center (WH-550A),
      401 M. St., SW, Washington, DC 20460.
                                         26

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U.S. EPA.  1985. Section V.C. Evaluation of Health Effects and Determination of RMCLs
      pp. 46944-46950 in National Primary Drinking Water Regulations; Synthetic Organic
      Chemicals; Inorganic Chemicals and Microorganisms.  Available from U.S.
      Environmental Protection Agency, Office of Water Resource Center (WH-550A), 401
      M. St., SW, Washington, DC 20460.

U.S. EPA.  1993a.  Great Lakes Water Quality Initiative Technical Support Document for
      Wildlife Criteria.  Available from U.S. Environmental Protection Agency, Office of
      Water Resource Center (WH-550A), 401 M. St., SW, Washington, DC 20460.

U.S. EPA.  19935.  Great Lakes Water Quality Criteria Initiative.  Appendix A:
      Uncertainty Factors in Great Lakes Water Quality Criteria Initiative Technical
      Support Document for Human Health Criteria and Values. NTIS #PB93-15468.
      ERIC: 3940.
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Tables to Appendix D to Part 132

TABLE D-l. Tier I Great Lakes Wildlife Criteria.
Substance
Criterion
DDT & Metabolites

Mercury

PCBs (total)

2,3,7,8-TCDD
0.87 pg/L

180 pg/L

17 pg/L

0.0096 pg/L
TABLE D-2. Exposure parameters for the five representative species identified for
protection.
Species      Body Wt.     Ingestion Rate
               (WtJ          (FJ
               (Kg)          (Kg/d)
       Drinking Rate   Trophic Level   %Diet
           (WJ        of Wildlife    at each
           (L/d)       Food Source    trophic
                                     Level
Mink
Otter
Kingfisher
Osprey
Eagle
1.0
8.0
0.15
1.5
4.5
0.15
0.9
0.075
0.3
0.5
0.099
0.64
0.017
0.077
0.16
3
3
4
3
3
4
100
50
50
100
100
100
                                        28

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 CHAPTERS
       Appendix to the Preamble—Great Lakes Water Quality
 Initiative Technical Support Document for Wildlife Criteria

 Note:  This appendix to part 132 contains background material and material intended to
 clarify portions of the regulation. It does not establish any additional regulatory
 requirements.

 I. Introduction

       The waters of the Great Lakes System provide vital resources not only to support
 numerous critical human activities and habitat for aquatic organisms, but also to sustain
 viable mammalian and avian wildlife communities.  In  order to assure that the quality of the
 waters in the System are adequate to support these uses, specific water quality criteria need
 to be set.

       The purpose of establishing water quality criteria for wildlife is to  determine surface
 water concentrations of toxicants that will remain protective of avian and mammalian wildlife
 populations that utilize waters of the Great Lakes System as a drinking and/or foraging
 source.  Specifically, each criterion is the highest calculated aqueous concentration of a
 toxicant which causes no significant reduction in the viability or usefulness (in a commercial
 or recreational sense) of a population of exposed animals over several generations. For the
 purpose of these regulations, this concentration is called the Great Lakes Wildlife Criterion
 (GLWC).

       Ideally, a safe concentration of a given pollutant would be  calculated for every
 species and the GLWC would be determined based on the distribution of these values across
 all species (an approach similar to that used in deriving criteria to  protect aquatic life,
 Stephan et al., 1985). Therefore, an approach similar to that proposed to  derive a noncancer
 human health criterion (section m.C.3 of appendix C to part 132 of this rule, Methodologies
 for Development of Human  Health Criteria and Values) was used in which representative
 wildlife species were selected to establish the basis for  employing interspecies uncertainty
 factors for extrapolation of toxicity data and to define specific exposure parameters.   Five
 Great Lakes basin wildlife species representative of avian and mammalian  species resident in
 the Great Lakes basin which are likely to experience significant exposure to  contaminants
 through the aquatic food web were identified. These species are the bald eagle, osprey,
belted kingfisher, mink, and river otter. A Wildlife Value (WV) is calculated for each
representative species (which is a safe concentration of a given pollutant) and then the
geometric mean of these values within each taxonomic class is determined. The GLWC is
 the lower of two class-specific means.

       To derive the WVs from which the GLWC is determined, scientific literature for the
toxicant of concern is reviewed for mammalian and avian toxicity studies that meet the
minimum toxicity database requirements.  A  tiered approach is used in the derivation of these
criteria. Tier I values are developed for chemicals with databases  providing a high level of

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certainty in quantifying concentrations at which adverse effects may be experienced by the
avian and mammalian wildlife communities.  EPA is proposing four specific Tier I criteria
that will be applicable across the Great Lakes System.  States and Tribes will be expected to
adopt into regulation these criteria (or more stringent values). They will also be expected to
adopt the procedure for developing Tier I values for additional substances.  EPA encourages
States and Tribes to adopt these Tier I values as criteria.

       Chemicals with less extensive data, or where the level of certainty is less, are subject
to Tier n values. States and Tribes will be expected to adopt, by regulation, the procedure
for developing Tier n values, rather than the numeric values die procedure generates.

n.  Calculation of Wildlife Values for Tier I Criteria and Tier n Value Development

A.   Derivation of Equation

       The equation  used to calculate Wildlife Values (WV), and  ultimately the GLWC, has
both a hazard and exposure component. The hazard component contains the NOAEL-the
highest tested dose of a substance which does not result in an observed adverse effect.  The
exposure routes considered  in this derivation are food and water ingestion.  The intake level
is dependent on organism size and therefore it is scaled to body weight.  The total toxicant
intake through these exposure routes is determined and then set equal to the NOAEL as
follows:
       Toxicant intake through drinking water = (WV x WJ/WtA             (Equation  1)
       Toxicant intake through food = (WV x FA x BAF)/WtA                 (Equation  2)
Where:
WV = Wildlife value in milligrams of substance per liter (mg/L).

WA = Average daily volume of water consumed in liters per day  (L/d) by the representative
       species identified for protection or the species identified as requiring greater
       protection.

FA  = Average daily amount of food consumed in kilograms per day (kg/d) by the
       representative species identified for protection or the species identified as requiring
       greater protection.

BAF = Aquatic life bioaccumulation factor for wildlife in liters per kilogram (L/kg).
       Chosen using guidelines for wildlife presented in appendix B to part 132 of this rule,
       the Methodology for Development of Bioaccumulation Factors.

WtA = Average weight in kilograms (kg) for the representative species identified for
       protection or  the species identified as requiring greater protection.
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 Equations one and two are combined to yield Equation three.
   NOAEL > (WV x WJ/WtA + (WV x FA x BAF)/WtA                    (Equation 3)
       Where:
       NOAEL = No observed adverse effect level in milligrams of substance per kilogram
 of body weight per day (mg/kg-d) as derived from mammalian or avian toxicity studies.

       Factoring and rearranging produces:
 WV < NOAEL x Wt.                                                     (Equation 4)
       WA + [FA x BAF]

       To account for differences in toxicity among species, the NOAEL is multiplied by the
 species sensitivity factor, SSF.  The final equation for the WV is:
 WV = [NQAEL x SSF1 x Wt^                                              (Equation 5)
       WA  + DFAxBAF]

 B.  Weight of the Test Animal, Representative Species, or Species Requiring Greater
 Protection

       The weight of the test animal may be needed to convert the NOAEL determined in
 the study to the correct units for use in the equation to derive a wildlife value. If a species is
 identified  as requiring greater protection and is not one of the representative species, its
 weight is needed for calculation of the GLWC. If this information is not given in the chosen
 study, the average weight of the test species shall be determined from available literature,
 including, if necessary, metabolic rate  models, such as those presented by Nagy (1987), and
 discussed  further, below.

 C.  Drinking and Feeding Rates for the Test Animal or Species Requiring Greater Protection

       A feeding and drinking rate for a species identified as requiring greater protection and
which is not one of the representative species identified for protection may also be needed for
calculation of the GLWC. These rates are needed to accurately predict exposure. When
consumption rates are given in the study of choice, they may be substituted directly into the
equation.  If this information is  not available from the chosen toxicity study, it shall  be
obtained from other appropriate literature concerning the species.  In some instances,
however, this information is not available directly and needs to be  estimated.  The following
reference may be consulted for studies done with domestic laboratory animals: Registry of
Toxic Effects of Chemical Substances (National Institute for Occupational Safety  and Health,
the latest edition).

       When insufficient data exist for other mammalian or avian species, the allometric
equations presented in appendix D to part 132 should be used to approximate  the needed
feeding or drinking rates.  These equations were adopted from  Calder and Braun  (1983), and
Nagy (1987).
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       When replicated data exist, best professional judgement will be used in the selection
of a single value. Barring that, the geometric mean of the data points will be utilized as the
representative value.

m.  Parameters of the Hazard Component of the Wildlife Criteria Methodology

A. Minimum Toxicity Database for Tier I Criteria Development

       The 90-day requirement for mammalian studies and the 28-day requirement for avian
studies are to ensure that the toxicity data on which a wildlife criterion is based exceeds an
acute exposure, which may underestimate the potency a compound would have following a
chronic exposure.  These minimum test length requirements are to be applied to both field
and laboratory studies.

B.  Minimum Toxicity Database for Tier II Wildlife Value Development

       For those substances for which Tier I criteria cannot be derived, all data from avian
and mammalian species may be considered in the development of Tier n values.  Subchronic
or chronic toxicity data shall be used whenever available to derive a no observable adverse
effect level (NOAEL) for Tier n values.  There are two major differences  in data
requirements for Tier n values: (1) The minimum database requirements presented for the
derivation of a Tier I wildlife criteria must only be met for one of the two  taxonomic classes
in order to derive a Tier n wildlife value;  and (2) a Tier n value may also be based on a
mammalian study which fulfills the requirements set forth for Tier I criteria excepting it may
have only a 28-day duration.

       LD50 and eight-day LC50 data may be used in support of subchronic and  chronic
toxicity data; however, neither a Tier I criteria nor a Tier n value shall be calculated solely
on the basis of LD50 or eight-day LC50 data.

C. LOAEL to NOAEL Extrapolations

       If a NOAEL in proper units is available from the scientific literature, it may be
substituted directly into the equation.  In many instances, however, a NOAEL is unavailable
and a LOAEL is available for a particular  animal. In these instances the LOAEL must be
adjusted to estimate a NOAEL and converted to proper units before being substituted into the
equation.

       The LOAEL is adjusted by dividing by an uncertainty factor which typically ranges in
value from 1.0 to 10 to lower the LOAEL into the range of the NOAEL.  Experimental
support of this concept is provided by Weil and McCollister (1963). A discussion and
endorsement of this concept can be found in Stokinger (1972) and Dourson and Stara (1983).
In addition, this concept is endorsed by EPA in the Federal Register  for Water Quality
Criteria Documents (45 FR 79353-79354, November 28, 1980) and in the National Drinking
Water Regulations (50 FR 46944-46946, November 13, 1985). Additional discussion on the
use of a LOAEL to NOAEL uncertainty factor and the determination of its magnitude is also

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 provided in appendix A to the Great Lakes Water Quality Initiative (GLWQI) Technical
 Support Document for Human Health Criteria and Values, which is available in the
 administrative record for this rulemaking.

 D.  Subchronic to Chronic Extrapolations

        In certain instances where only subchronic data are available, a subchronic to chronic
 uncertainty factor may be used to account for the uncertainty in extrapolating from a
 subchronic NOAEL to a chronic NOAEL.  The value of the uncertainty factor is within the
 range of 1.0 to 10, depending on the dose-response of the adverse effect. The subchronic
 NOAEL is divided by the uncertainty factor. This factor may be used when assessing highly
 bioaccumulative chemicals, where toxicokinetic considerations suggest that a bioassay of
 limited length may underestimate hazard.  This concept and the use of a 10-fold uncertainty
 factor is endorsed by EPA in the Federal Register for Water Quality Criteria Documents (45
 FR 79353-79354, November 28, 1980) and in the National Drinking Water Regulations (50
 FR 46944-46946, November 13, 1985).  Additional discussion on the use of a subchronic to
 chronic uncertainty factor is also provided in appendix A to the Great Lakes Water Quality
 Initiative Technical Support Document for Human Health Criteria and Values, which is
 available in the administrative record for this rulemaking.

 E. Species Sensitivity Factor

        The NOAEL shall be adjusted to accommodate differences in interspecies toxicity
 with the use  of an uncertainty factor. This adjustment may be necessary since the toxicity
 information upon which a criterion is developed will not necessarily be based on a study
 using the representative wildlife species or the species identified as requiring greater
 protection.  In order to provide protection for the representative species or the species
 requiring greater protection, an uncertainty factor called the species sensitivity factor (SSF)
 shall be used the value of which shall be based on the physicochemical, toxicokinetic and
 toxicodynamic properties of the substance in question.  The value of the SSF shall also be
 based on the amount and quality of available toxicological data—both the duration and quality
 of available studies and the diversity of species for which data is available. Toxicity
 information for chemicals which operate by the same mode of action can also be considered
 in deriving the SSF for a given chemical.  The SSF is not intended to adjust for potential
 differences with regard to body weight and food and water consumption rates between the
 test species and the representative species or species requiring greater protection.  The factor
 selected shall reflect the uncertainty with which the available toxicity data are appropriate for
 the representative species or the species requiring greater protection.

       For Tier I wildlife criteria, the SSF generally shall be used for extrapolating toxicity
 data across species within a taxonomic class and have a value within the range of 0.01 and
 1.0.  Use of a SSF outside of this  range is prohibited unless approved by EPA.  An
 interclass extrapolation employing a SSF may be used for a specific chemical if is can be
 supported by a validated biologically-based dose-response model, incorporating acceptable
endpoints, for a chemical analog that acts under the same mode of toxic action.
                                          33

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       For Tier n wildlife values, interclass extrapolations are pennitted.  Because of the
uncertainties in performing interclass extrapolations, the SSF for calculating Tier n values
may not be greater than 1.0 but may be lower than 0.01 without requiring a written
justification.  It is stressed that Tier n values are by definition and design conservative. Tier
n values can be derived when subchronic or chronic data are available from only one
taxonomic class; however, because there is more uncertainty in performing interclass
extrapolation, a more conservative SSF may be applied.

       To determine the proper range for the species sensitivity factor, LDSO data were
reviewed for approximately 50 chemicals and chronic toxicity data were reviewed where
available. Table I of the annex contains LDSO data for nine pesticides, PCBs (Aroclor 1242)
and 2,3,7,8-tetrachlorodibenzo-p-dioxin. This table demonstrates how  toxicity from certain
chemicals differs among species. Table n of this annex contains chronic toxicity data for
organomercury compounds in mammalian species.  These data support both the use of an
interspecies uncertainty factor and the range of the SSF established within this procedure.

       In application, a database containing both chronic and reproductive/developmental
data for a diversity of species may require a SSF of between 0.1 and 1.0.  If these data are
from numerous species and represent the most sensitive mammalian and avian species, the
SSF may be equal to 1.0.

IV.  Parameters of the Exposure Component of the Wildlife Criteria Methodology

A.  Bioaccumulation Factors

       A bioaccumulation factor (BAF) is necessary to estimate the concentration of the
chemical in the wildlife food source based on its concentration in the water source.  The
procedure to derive the BAF is specified in appendix B to part 132 of this rule.  This
methodology specifies that, in general, trophic level three and four BAFs are used in the
derivation of wildlife values, although options to use plant or other trophic level BAFs are
permitted based on the identification of species requiring greater protection which are not
obligate piscivorous or are not likely to consume only fish species at trophic levels three or
four.

V.   Determination of Species Identified for Protection and Associated Exposure
Parameters

       Wildlife exposure to environmental contaminants in aquatic systems can be quite
variable depending on natural history characteristics of species and on animal physiology.
Furthermore, for most species there are few data to estimate exposure in nature (e.g.,
ingestion rates of natural foods, field metabolic rates).  The procedure outlined below
integrates appropriate exposure information for a broad array of species with variable
exposure scenarios and was used to  determine representative species identified for protection
in deriving the Great Lakes Wildlife Criteria.  This analysis  also supports the WV derivation
procedure which reflects an approach similar to the human non-carcinogen water quality
criteria derivation procedure.

                                          34

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 A.  Selection of Species Identified for Protection

        The analysis described in this section was performed to determine representative
 avian and mammalian species of the Great Lakes basin which are likely to experience
 significant exposure to contaminants in aquatic ecosystems through the food chain.  As a
 consequence, emphasis is on species with foraging behaviors and trophic levels of their
 forage sources which suggest high exposure to contaminants.  Therefore, the wildlife species
 of primary concern are piscivorous.

        In general, small endotherms have a higher ingestion rate relative to body mass than
 large endotherms, because small animals generally have a larger surface area to volume ratio
 and lose proportionately more energy as heat. This suggests that small animals would be
 exposed to contaminants to a greater degree than large animals, and would always be at a
 higher level of risk. However, small piscivorous are generally size-limited predators and
 feed on smaller fish in a lower trophic status than larger piscivorous.  Since the concentration
 of bioaccumulative pollutants is usually less at lower trophic levels, it can not be assumed
 that small animals have a greater exposure. Therefore, to adequately predict exposure,
 information on animal size, food habits, and behavior is needed.

       Determinations were made of representative species that reside in the Great Lakes
 basin, based on animal size (small, medium, and large) and foraging style.  Animals with
 different foraging styles may also have different morphologies and activity patterns that
 ultimately influence food or water ingestion rates and other factors that determine exposure
 to contaminants.

        1. Selection of Avian Species. Piscivorous avian species can be classified into three
 general types of foraging  styles; raptorial predators, diving and swimming predators, and
 wading, "sit-and-wait" predators.  Some species which reside in the Great Lakes basin and
 exhibit each of these foraging styles are listed here:
       a. Raptorial:  bald eagle, osprey, kingfisher and common tern;
       b. Diving:  double-crested cormorant, common loon, common  merganser and red-
       breasted merganser; and
       c. Wading:  great blue heron and green-backed heron.

       Exposure data with sufficient detail to make reasonable exposure estimates for six
 Great Lakes basin piscivorous birds was obtained: bald eagle, osprey,  common merganser,
common loon, double-crested cormorant and belted kingfisher.  These species represent two
of the three foraging styles identified.  Analysis of these data indicate that the ingestion rates
are proportional to the animal mass and the differing foraging styles do not contribute to
differences in the ingestion rate.  A representative sample of the
variability in bird exposure to contaminants in water can be gained by calculating  WVs for
the three raptorial species (eagle, osprey and kingfisher) which represent the range and
extremes in body size.  The additional data, since it is only for a small number of species,
was not used because it could skew the distribution.
                                           35

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       2. Selection of Mammalian Species.  Two mammals were identified in the Great
Lakes basin which are piscivorous and therefore likely to experience significant exposure to
contaminants in aquatic food chains—the mink and river otter. The two species have
different body sizes (adult otters are six-to-eight times larger than adult mink), and different
food habits.  Wildlife Values should be calculated for both mammal species.  The mink has a
larger food ingestion rate relative to body size than the otter.  However, it is unlikely that
mink have a diet that is comprised solely of fish from the higher trophic level as is predicted
for the otter. Therefore, calculating WVs for both mammals may account for the variability
in exposure that likely occurs in mammals.

B.  Derivation of Exposure Parameters and Body Weights for Species Identified for
Protection

       1. Bald Eagle (Haliaeetus leucocephalus). Adult eagles weigh from 3.0 to 6.3 kg
with an average adult weighing about 4.5 kg.  (Bortolotti, 1984; Stalmaster and Gessaman,
1984; Palmer, 1988).

       There have been several estimates of food ingestion rates of captive and free-ranging
eagles.  Stalmaster and Gessaman (1982) found that captive eagles consumed about 9.2
percent of their body mass in fish each day (approximately 414 g/d).  However, by weighing
fish carcasses before and after they were fed upon by free-ranging eagles, Stalmaster and
Gessaman (1984) estimated that eagles wintering on the Nooksack River, WA, consumed
about 490 g of fish each day. Using models produced by Gessaman and Stalmaster (1984),
Craig et al. (1988) estimated that adult eagles wintering along the lower Connecticut River,
CT, consume about 520 g of food per day.  Therefore, it is assumed that a typical adult
eagle consumes about 500 g of fish per day.

       The water ingestion rate is derived from the allometric equation presented in appendix
D to part 132 and is 0.16 L/d.

       2. Ospery  (Pandion haliatus).   Adult ospreys weigh from 1.1 kg to 2.0 kg with a
typical adult weighing approximately 1.5 kg (Newell  et al.,  1987; Palmer, 1988; Poole,
1989).

       As reviewed by Palmer (1988), adult osprey consume 286 kcal/d.  Assuming the
metabolizable energy in  fish is approximately 1 kcal/g (Palmer, 1988; Stalmaster and
Gessaman, 1982), osprey require 286 g of fish per day.  A  review of data for European
Ospreys, summarized by Palmer, 1988, suggested that food requirements were about 300 to
400 g/d. Nagy (1987) presents models to calculate field metabolic rates (FMRs) of birds and
mammals based on body weights.  The equation for calculating the FMR (in kcal/bird-d) of a
non-passerine bird is as follows:
       log FMR (kcal/bird-d) = 0.0594 -I- 0.749 log Wt (g)
       where Wt is in g, wet weight.

       The Nagy (1987) model predicts that osprey require 274 g of fish per day, assuming
osprey weigh 1500 g and the metabolizable energy in fish is 1 kcal/g.  Also, Newell et al.

                                          36

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 (1987) estimated that osprey would require 300 g/d assuming birds consume 20% of their
 body weight each day. Therefore, it appears that a reasonable estimate of food ingestion rate
 for adult ospreys is approximately 300 g/d.

       The water ingestion rate is derived from the allometric equation presented in appendix
 D to part 132 of this rule and is 0.077,L/d.

       3.  Belted Kingfisher (Ceryle alcyon).  The average adult belted kingfisher weighs
 approximately 0.15 kg (Fry, 1980; Dunning, 1984).

       Alexander (1977) reviewed the literature and estimated that adult Belted Kingfishers
 may consume up to 50 percent of their body weight in fish each day.  This would equate to
 approximately 75 g/d.  Since this was an estimate, the Nagy (1987) model was applied to
 calculate the FMR in kcal/d for a non-passerine bird:
 log FMR (kcal/bird-d) = 0.0594 + 0.749 log Wt (g).

       Assuming kingfishers weigh 150 g, and that the metabolizable energy in fish is 1
 kcal/g (Stalmaster and Gessaman,  1982; Palmer, 1988), the Nagy model predicts that birds
 would require about 50 g/d. Therefore, a reasonable  estimate of the kingfisher food
 ingestion rate would be about 75 g of fish per day.

       The water ingestion rate is derived from the allometric equation presented in appendix
 D to part 132  and is 0.017 L/d.

       4.  Mink (Mustela vison).  Adult male mink range from 0.9 to  1.6 kg, and females
 range from 0.6 to 1.1 kg (Linscombe et al., 1982).  Therefore, it is assumed that an average
 adult mink has a body mass of 1.0 kg (see also Newell et al., 1987).

       Estimates of food ingestion rates of captive mink range from about 12 percent to 16
percent of the adult body weight per day (Aulerich et  al., 1973; Bleavins and Aulerich,
 1981). Therefore, it will be assumed that a one kg adult mink consumes about 150 g of food
per day (Aulerich et al., 1973; Newell et al., 1987).

       The water ingestion rate is derived from the allometric equation presented in appendix
D to part  132 and is 0.099 L/d.

       5.   River Oner (Lutra canadensis).  Adult otters range from 5 kg to 15 kg, with a
typical adult weighing 8 kg (Lauhachinda, 1978; Toweill and Tabor, 1982).

       Toweill and Tabor  (1982) reviewed two studies reporting food ingestion rates of
captive otters. North American otters were  reported to require about 700 to 900 g of
prepared food each day, while European otters consumed 900 to  1000 g of live fish each
day. Therefore, it is assumed that otter consume about 900 g of food per day.

       The water ingestion rate is derived from the allometric equation presented in appendix
D to part  132 and is 0.64 L/d.

                                          37

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C.  Derivation of Dietary Trophic Levels for Species Identified for Protection

       1. Bald Eagle (Haliaeetus leucocephalus).  Bald Eagles are known to consume a
variety of foods including fish, waterfowl, small mammals, and carrion. However, if
available, fish are their principal food and large fish may make up 100 percent of their diet
(Newell et al., 1987; Palmer, 1988; Kozie and Anderson,  1991).  Therefore, it is assumed
that eagles consume only trophic level 4 fish.

       2. Ospery (Pandion haliatus). The  diet of Osprey is almost 100 percent live fish,
concentrating on fish weighing 150-300 g (Palmer, 1988 and Poole,  1989).  Therefore, it is
assumed that Osprey are consuming only trophic level 3 fish.

       3. Belted Kingfisher (Ceryle alcyon).  Kingfishers may eat a variety of foods
including fish, amphibians,  and insects. However, small fish are known to comprise roughly
90 percent of their total diet (Alexander, 1977). Therefore, it is assumed that kingfishers
have a diet of only trophic level 3 fish.

       4. Mink (Mustela vison).  Mink are opportunistic carnivores (Linscombe et al.,
1982); however, aquatic organisms sometimes comprise almost 100 percent of their diet
with fish usually making up less than 50 percent of their total intake (Aulerich, 1973;
Alexander, 1977; Linscombe et al.,  1982; Newell  et al., 1987). It is assumed that the diet of
mink foraging in habitats comprising the shores of the Great Lakes and major tributaries is
made up of trophic level 3 fish.

       5. River Otter (Lutra canadensis). The bulk of the otter's diet is composed of fish
(typically greater than 90 percent) with other aquatic organisms making up lesser  portions
(Toweill and Tabor, 1982; Newell et al.,  1987). It is assumed that otters consume a diet
composed of 50 percent trophic level 3 and 50 percent trophic level 4 fish.
                                          38

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TABLE I
SENSITIVITY OF
Chemical
Aldrin




Chlordane


DDT






Dieldrin











Endrin






SPECIES BASED ON LDjo
Species
Fulvous whistling duck
Mallard
Bobwhite
Pheasant
Mule Deer
Mallard
California Quail
Pheasant
Bullfrog
Mallard
California Quail
Japanese Quail
Pheasant
Sandhill Crane
Rock Dove
Canada Goose
Fulvous Whistling Duck
Mallard
California Quail
Japanese Quail
Pheasant
Chukar
Gray Partridge
Rock Dove
House Sparrow
Mule Deer
Domestic Goat
Mallard
Sharp Tailed Grouse
California Quail
Pheasant
Rock Dove
Mule Deer
Domestic Goat
DATA
Dc« tog/kg)
29.2
520
6.59
16.8
18.8-37.5
1,200
14.1
24.0-72.0
72,000
72,240
595
841
1,334
71,200
74,000
< 141
100-200
381
8.78
69.7
79.0
25.3
8.84
26.6
47.6
75-150
100-200
5.64
1.06
1.19
1.78
2.0-5.0
6.25-12.5
25.0-50.0

F95% Conf. Int.ll
[22.2-38.4]
[229-1,210]
[5.00-8.66]
[14.1-20.0]

[954-1,510]
[9.14-21.7]



[430-825]
[607-1,170]
[894-1,990]





[6.47-11.9]
[40.0-121]
[21.6-289]
[15.2-42.2]
[1.24-62.8]
[19.2-36.9]
[34.3-66.0]


[2.71-11.7]
[0.552-2.04]
[0.857-1.65]
[1.12-2.83]



                                 39

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TABLE I (continued)
Hexachlorobenzene

Parathion

















PCB
(Aroclor 1242)




Temephos







2,3,7,8-TCDD


Mallard
Pheasant
Fulvous Whistling Duck
Mallard
Mallard
Mallard
Mallard
Mallard
Mallard Duckling (MM)
Sharp Tailed Grouse
California Quail
Japanese Quail
Pheasant
Pheasant
Chukar
Gray Partridge
Rock Dove
House Sparrow
Mule Deer
Domestic Goat
Mallard Duck
Pheasant
Mink
Ferret
Rat
Rabbit
Bullfrog
Mallard
California Quail
Japanese Quail
Pheasant
Chukar
Rock Dove
House Sparrow
Guinea Pig
Rat
Rhesus Monkey
71,414
118
0.125-0.250
2.40
1.90
2.34
1.44[
1.44[
0.898
5.66
16.9
5.95
12.4
>24.0
24.0
16.0
2.52
3.36
22.0-44.0
28.0-56.0
2,098
2,078
1.0-8.6
>20
0.8-11.0
8.7
> 2,000
79.4
18.9
84.1
35.4
240[
50.1
35.4
0.6-2 ug/kg
22-45 ug/kg
<70 ug/kg

[93.6-148]

[1.67-4.01]
[1.37-2.64]
[1.88-2.92]
[1.13-1.83]
[1.16-1.80]
[0.770-1.05]
[3.46-9.24]
[12.2-23.5]
[3.38-10.5]
[10.1-15.2]

[16.8-34.2]
[4.00-64.0]
[1.82-3.50]
[2.43-4.66]









[38.5-163]
[15.0-23.8]
[60.6-116]
[25.5-49.0]
[110-521]
[16.7-150]
[8.85-141]



         40

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                                  TABLE I (continued)
2,3,7,8-TCDD (cont.) Dog
                   Mouse
                   Rabbit
                   Hamster
                         100-200 ug/kg
                         114-284 ug/kg
                         115 ug/kg
                         1,157-5,051 ug/kg
Toxaphene











Fulvous Whistling Duck
Mallard Duckling
Mallard
Sharp Tailed Grouse
Bobwhite
California Quail
Pheasant
Gray Partridge
Sandhill Crane
Horned Lark
Mule Deer
Domestic Goat
99.0
30.8
70.7
19.9
85.5
23.7
40.0
23.7
100-316
581
139-240
>160
[37.2-264]
[23.3-40.6]
[37.6-133]
[14.1-28.2]
[59.3-123]
[11.9-47.4]
[20.0-80.0]
[20.0-28.3]

[425-794]


Adopted from Eisler,  1986a,b and Hudson, et al. 1984.
TABLEH
TOXICITY OF ORGANOMERCURY COMPOUNDS TO SELECTED
MAMMALIAN SPECIES
Species
Dose
 Effect
Dog
Cat
Pig
Rhesus Monkey
Mink
River Otter
0.1-0.25 mg/kg
0.25 mg/kg
0.5 mg/kg
0.5 mg/kg
1.0 mg/kg
> 2.0 mg/kg
Stillbirths
Death
Stillbirths
Maternal Toxicity
Death
Death
Adopted from Eisler, 1987.
                                          41

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VI.  References

Alexander, G.  1977. Food of vertebrate predators of trout waters in north central lower
       Michigan. Michigan Academician. 10:181-195.

Aulerich, R. J., R. K. Ringer and S. Iwamoto.  1973. Reproductive failure and mortality in
       mink fed on Great Lakes fish. J. Reprod. Pert. (Suppl.) 19:365-376.

Bleavins, M. R. and  R. J. Aulerich.  1981. Feed consumption and food passage in mink
       (Mustek vison) and European ferrets (Mustela putorius furo). Lab. Animal Sci.
       31:268-269.

Bortolotd, G. R. 1984. Sexual size dimorphism and age-related size variation in bald
       eagles.   J. Wildl. Manage. 48:72-81.

Calder ffl, W. A., and E. J. Braun.  1983. Scaling of osmotic regulation in mammals and
       birds. American Journal of Physiology.  244:601-606.

Craig, R. J., E. S. Mitchell and J.  E. Mitchell.  1988. Time and energy budgets of bald
       eagles wintering along the Connecticut River.  J. Field Ornithol. 59:22-32.

Dourson, M. L. and  J. F. Stara.  1983.  Regulatory history and experimental support  of
       uncertainty (safety) factors.  Regulatory Toxicology and Pharmacology. 3:224.

Dunning, J.  B.   1984.  Body weights of 686 North American birds, Monograph #1, Western
       Bird Banding  Association.

Eisler, R.  1986a. Dioxin hazards to fish, wildlife, and invertebrates: a synoptic review.
       U.S.  Fish and Wildlife Service Biological Report. 85(1.8): 37pp.

Eisler, R.  19865. Polychlorinated biphenyl hazards to fish, wildlife, and invertebrates: a
       synoptic review.  U.S. Fish and  Wildlife Service. Biological Report.  85(1.7): 72 pp.

Eisler, R.  1987.  Mercury hazard to fish, wildlife and invertebrates: a synoptic review.
       U.S.  Fish and Wildlife Service Biological Report. 85(1.10): 90pp.

Fry, C. 1980.  The  evolutionary biology of kingfishers (Alcedinidea). In: The Living Bird,
       1979-1980. The Laboratory of Ornithology, Cornell Univ., Ithaca, pp. 113-160.

Great Lakes Water Quality Initiative. Appendix A:  Uncertainty Factors. JQ Great Lakes
       Water Quality Criteria Initiative  Technical Support Document for Human Health
       Criteria  and Values.  NTIS #PB93-15468. ERIC: 3940.

Hudson, R. H., R. K. Tucker, and M.  A. Haegele.  1984.  Handbook of toxicity of
       pesticides to wildlife, U.S. Fish  and Wildlife Service, Resource Publication #153,  90
       pp.

                                          42

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 Kozie, K. D. and R. K. Anderson.  1991.  Productivity, diet, and environmental
       contaminants in bald eagles nesting near the Wisconsin shoreline of Lake Superior.
       Arch. Environ.  Contain. Toxicol. 20:41-48.

 Lauhachinda, V.  1978. Life history of the river otter in Alabama with emphasis on food
       habits. Ph.D. dissertation. University of Alabama, Auburn,  AL. 169 pp.

 Linscombe, G., N.  Kinler and R.  Aulerich.  1982. Mink. In: J. Chapman and G. Feldhamer
       (eds.), Wild Mammals of North America: Biology, management and economics.
       John Hopkins Univ. Press, Baltimore, pp. 629-643.

 Nagy, K. A. 1987. Field metabolic rate and food requirement scaling in mammals and
       birds. Ecological Monographs.  57(2): 111-128.

 National Institute for Occupational Safety and Health.  Latest edition.  Registry of Toxic
       Effects of Chemical Substances (available only on microfiche or as an electronic data
       base). Cincinnati, OH.

 Newell, A. J., D. W. Johnson and L. K. Allen.  1987.  Niagara River biota contamination
       project:  Fish flesh criteria for piscivorous wildlife. New York State, Division of
       Environmental Contaminants. Technical Report 87-3.

 Palmer, R. S. Editor.  1988.  Handbook of North American birds:  Volume 4.  Yale
       University Press. 433 pp.

 Poole, A. F. 1989.  Ospreys:  A natural and unnatural history. Cambridge, MA: Cambridge
       University Press.

Registry of Toxic Effects of Chemical Substances.  Latest edition.  National Institute for
       Occupational Safety and Health.  Cincinnati, OH.

Stalmaster, M. V. and J. A. Gessaman.  1982.  Food consumption and energy requirements
       of captive bald eagles.   J. Wildl. Manage. 46:646-654.

Stalmaster, M. V. and J. A. Gessaman.  1984.  Ecological energetics and foraging behavior
       of overwintering bald eagles.  Ecol. Monogr. 54:407-428.

Stephan,  C.  E., D. I. Mount, D. J. Hansen, J. H. Gentile, G. A. Chapman, and W. A.
       Brungs.  1985.  Guidelines for deriving numerical national water quality criteria for
       the protection of aquatic organisms and their uses. PB85-227049.  National Technical
       Information Service. Springfield, VA.

Stokinger, H.E. 1972.  Concepts of thresholds in standard setting.  Arch. Environ. Health.
       25:153-157.
                                         43

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Toweill, D. E. and J. E. Tabor.  1982.  River otter.  In: J. Chapman and G. Feldhammer
       (eds.), Wild Mammals of North America.  John Hopkins Univ. Press, Baltimore,  pp.
       688-703.

U.S. EPA.  1980. Appendix C.  Guidelines and Methodology Used in the Preparation of
       Health Effect Assessment Chapters of the Consent Decree Water Criteria Documents.
       pp. 79347-79357 in Water Quality Criteria Documents; Availability.  45 FR 79318-
       79378.  Friday, November 28, 1980.

U.S. EPA.  1985. Section V.C.  Evaluation of Health Effects and Determination of RMCLs
       pp. 46944-46950 in National Primary Drinking Water Regulations; Synthetic Organic
       Chemicals; Inorganic Chemicals and Microorganisms. 50 FR 46936-47022.
       Wednesday, November 13, 1985.

Weil, C.S., and D.D. McCollister, 1963. Relationship between short and long-term studies
       in designing an effective toxicity test.  Agric. Food Chem.  11:486-491.
                                        44

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 CHAPTER 4
       Section VIE of Preamble to  Great Lakes Water Quality
 Guidance: General Implementation Procedures

 A. Site-Specific Modifications to Criteria

       National guidance provided in the "Water Quality Standards Handbook" (1983) (the
 Handbook) indicates that States may modify generally applicable State criteria and set site-
 specific water quality criteria for the protection of aquatic life when: the local water quality
 parameters such as Ph, hardness, temperature, color, etc., alter the biological availability
 and/or toxicity of a pollutant; and/or the sensitivity of the local aquatic organisms (i.e., those
 that would live in the water absent human-induced pollution) differs significantly from the
 species actually tested in developing the criteria. This Handbook is available in the
 administrative record for this rulemaking. Copies are also available upon written request to
 the address listed in section Xffl of this preamble.  State-wide water quality criteria for
 aquatic life may be unnecessarily stringent or underprotective in a given water body if the
 physical and chemical characteristics of the water body ameliorate or enhance the biological
 availability and/or toxicity of a given chemical. In addition, species capable of living at a
 particular site, if there were no human-induced pollution, may be more or less sensitive than
 those species represented in the development of the State-wide criteria.  Developing site-
 specific criteria for aquatic life is a way of taking unique conditions of a specific portion of a
 water body into account so that criteria adequately protect aquatic life from acute and chronic
 effects. Chapter 4 of the Handbook provides procedures for setting site-specific criteria for
 aquatic life which may be utilized as a basis for establishing water quality standards.  Using
 those procedures, the resulting chronic or acute aquatic life  criteria  may be more or less
 stringent than the otherwise applicable State criteria.

       There is presently no such specific guidance regarding site-specific modifications to
 human health water quality criteria.  Additionally, there is presently no National guidance for
 deriving wildlife water quality criteria or site-specific modifications to wildlife criteria.
However, present regulations do allow States to modify any criteria to reflect site-specific
conditions provided that the modified criteria are protective of designated uses and based on
 sound scientific rationale (40 CFR 131.11).  One of the issues that States might consider in
developing site-specific modifications to human health criteria,  for example, is local fish
consumption rates.  (See, generally, memorandum from LaJuana S. Wilcher to Regional
Water Management Division Directors, dated January 5, 1990, which is available in the
administrative record for this rulemaking.)

       National water quality criteria are based upon data from, and assumptions specifically
applicable to, the entire United States. The Great Lakes criteria/values proposed in the
proposed Guidance differ from the National  criteria in part because  they were derived using
data and assumptions relevant to the Great Lakes System. For example, certain aquatic life
criteria/values have been lowered to protect commercially or recreationally important species
within the Great Lakes System (e.g., steelhead rainbow trout).  As another example, BAFs
used in developing human health criteria/values for the Great Lakes System assume a fish

                                         45

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lipid content of five percent based on Great Lakes-specific data instead of the National
average lipid content of three percent used for the derivation of National criteria. The
purpose of using Great Lakes-specific data and assumptions in deriving criteria/values is to
more accurately calculate ambient criteria levels that are protective of aquatic life, wildlife
and humans within the Great Lakes System.

       Even though the Great Lakes criteria/values already reflect Great  Lakes-based
modifications of the National criteria, there may be local areas within the Great Lakes
System where conditions vary sufficiently from the assumptions underlying the methodologies
for deriving Tier I criteria and Tier n values to merit the application of more narrowly
applicable site-specific criteria.  Procedure 1 of the proposed Implementation Procedures
specifies the circumstances where a State may develop site-specific modifications to the Great
Lakes aquatic life, human health and wildlife criteria as well as bioaccumulation factors.
The proposed  Implementation Procedures allow modifications to be made to acute or chronic
aquatic life criteria/values in a manner consistent with Chapter 4 of the Handbook.  This
Handbook only covers site-specific water quality criteria for the protection of aquatic life.
Consistent with that guidance, site-specific modifications to acute and chronic aquatic life
criteria/values for the Great Lakes System under the proposed Guidance may result in more
or less stringent aquatic life criteria/values than those calculated using the Great Lakes
aquatic life methodology.

       The Handbook only sets forth procedures  for developing site-specific modifications to
aquatic life criteria when such modifications are appropriate because either local  water
quality parameters alter the biological availability or toxicity of a pollutant, or the sensitivity
of local aquatic organisms differ significantly from the species actually tested in developing
criteria.  Proposed implementation procedure 1, however, goes beyond the Handbook by also
allowing the Great Lakes States and Tribes to develop site-specific modifications to chronic
aquatic life criteria/values for the Great Lakes System to reflect local physical and hydrologic
conditions.  Specifically, the Great Lakes States and Tribes would be allowed to  also develop
site-specific modifications to chronic aquatic life criteria/values by showing that either
hydrologic conditions or physical conditions related to the natural features of a water body,
such as lack of a proper substrate, cover, flow, depth, pools, riffles, and the like, unrelated
to ambient water quality, preclude aquatic life from remaining in the site for 96 hours or
more.  These site-specific conditions may also be taken into account in determining whether
a discharge  must comply with the chronic whole effluent toxicity requirements specified in
proposed procedure 6. A.2.  This provision is discussed in section VHI.F of the preamble.

       As explained above in the section of this preamble on the  Applicability of the Tier I
and Tier n Criteria/Values,  the Initiative Steering Committee intended that the States be
given additional flexibility to modify chronic aquatic life criteria/values where physical and
hydrologic conditions prevent aquatic life from remaining in a specific water body for 96
hours or more. The Steering Committee was concerned that the chronic aquatic  life
criteria/values would be unnecessarily stringent in protecting aquatic life  in such  locations
because the  chronic aquatic life methodologies assume that aquatic life are exposed to
pollutants in a specific water body for at least 96 hours. Consistent with the Steering
Committee deliberations, the proposed Guidance  allows the States to develop site-specific

                                          46

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 modifications to the chronic aquatic life criteria/values to reflect local physical and
 hydrologic conditions.

       EPA believes that it is possible that there may be sites within the Great Lakes System
 where aquatic life will not remain at the site for more than 96 hours.  Consequently, aquatic
 life can be protected from suffering chronic health effects at such sites by criteria/values less
 stringent than those developed under the proposed Great Lakes Guidance. Similarly, in sites
 where conditions preclude all but a few forms of aquatic life from living in a specific site, it
 is possible that the few forms of aquatic life living at the site may be protected by less
 stringent criteria/values.  Because the physical and hydrologic condition justification for the
 exception to procedure 6. A.2 of appendix F is functionally equivalent to a justification for
 the removal of a designated use at 40 CFR  131.10(g)(2), (4) and (5), EPA expects this
 exception will typically be used for waters where a full aquatic life use is unattainable.
 States must ensure that the application of this exception does not impair the water quality of
 downstream waters.

       The proposed Great Lakes Guidance does not provide for the same flexibility in terms
 of site-specific modifications to  the wildlife  and  human health criteria/values or to
 bioaccumulation factors as is available for aquatic life criteria/values.  The proposed
 Guidance restricts site-specific modifications to human health criteria/values, wildlife
 criteria/values, or bioaccumulation factors to only those which would increase the level of
 protection for humans and wildlife. The proposed Guidance, in allowing States to adopt less
 stringent criteria/values for aquatic life, but not for human health and wildlife, is  consistent
 with the Steering Committee's proposal.

       EPA believes that although less stringent site-specific criteria/value modifications can
 be justified for aquatic life, similar justifications may not exist with respect to less stringent
 wildlife and human health criteria/values or BAFs.  For example, EPA does not believe that
 there are natural conditions in the Great Lakes System which preclude humans and wildlife
 from consuming fish and recreating in specific sites.  Similarly, even if there may be local
 populations of humans and wildlife less exposed to toxicants than assumed in deriving the
 State-wide criteria, a less stringent site-specific modification may not be appropriate given
 the mobility of humans and wildlife into and out of these localized areas.  Instead, EPA
 assumes that, due to their mobility, humans  and  wildlife feed from and recreate in all
portions of the Great Lakes System. EPA believes that these assumptions are reasonable and
appropriate in light of the goals and objectives of the Clean Water Act and the Great Lakes
Water Quality Agreement. However, EPA  requests comment on these assumptions.

       The proposed Guidance allows Great Lakes States and Tribes to adopt site-specific
 modifications allowing for application of less stringent aquatic life criteria/values where local
 water quality parameters alter the biological availability and/or toxicity of a pollutant, but
does not allow similar site-specific modifications for human health and wildlife
criteria/values.   This proposal is consistent with  the proposal of the Steering Committee.  In
those cases where the biological availability  and/or toxicity of a pollutant is decreased by
local water quality conditions (e.g., pH, hardness, alkalinity, suspended solids), a less
stringent criteria/value for aquatic life will adequately protect aquatic organisms.  The

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proposed Guidance reflects a more conservative approach with respect to humans and
wildlife by allowing only more stringent site-specific modifications.  EPA believes that this
conservative approach is appropriate because of the mobility of humans and wildlife and their
potential for exposure to these pollutants in different areas of the Great Lakes basin. In
addition, there is not adequate information to quantify the total environmental uptake by
humans and wildlife from different exposure routes. In light of these uncertainties, EPA
proposes to use an approach that may result in human health and wildlife criteria/values
which are somewhat overprotective in those cases where local water quality parameters
decrease the biological availability and/or toxicity of a water body. This approach would err
on the side of being overprotective rather than underprotective.  EPA invites comment on
whether the proposed approach for humans and wildlife is reasonable or whether less
stringent site-specific modifications should be allowed under certain circumstances.

       Specifically, EPA requests comment on whether the proposed Guidance should be
modified to allow for development of less stringent site-specific  modifications to all types of
criteria/values (including human health and wildlife) and BAFs under any of the scenarios
described below or under any other  scenarios.  Comment is requested on whether less
stringent site-specific modifications should be allowed for human health and wildlife
criteria/values where local water quality parameters decrease the biological availability and/or
toxicity of a pollutant.   EPA invites specific comment on adding to the human health and
wildlife provisions the same text as appears in  section A.I.a of procedure 1 of appendix F
for aquatic life.  EPA also invites comment on whether less stringent site-specific
modifications should be allowed for bioaccumulative pollutants where local physical or
hydrologic conditions do not allow aquatic life that may be consumed by humans or wildlife
to be present in the water body long enough to reach steady-state bioaccumulation.  EPA
further invites comment on whether less stringent site-specific modifications should be
allowed for bioaccumulation factors if reliable data shows that local bioaccumulation is lower
than the system-wide value.

       EPA also invites comment on whether it should allow in  the final Great Lakes
Guidance the development of less stringent site-specific modifications to the aquatic life
criteria/values, as proposed today. Eliminating the option would enhance consistency of
criteria in the Great Lakes System.

       The proposed Guidance for wildlife criteria/values states  that modifications may be
made on a site-specific basis to provide an additional level of protection for a species
determined to require greater protection, for any reason.  The proposed Guidance specifies
that such site-specific modifications  may be accomplished through the incorporation of an
additional uncertainty factor in the equation for the wildlife  value. The text presented below
provides additional guidance on the  equation for the calculation of the wildlife value and is in
keeping with the intent of the Initiative Committees. EPA requests comment on the use of
the following alternate text to replace  the text of procedure  1.A.2 of appendix F of the
proposed Guidance.

       Wildlife criteria or values may be modified on a site-specific basis to provide an
additional level of  protection for a species determined to require greater protection, for any

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 reason.  This may be accomplished through the use of an additional uncertainty factor in the
 equation for the wildlife value as presented below:

                        WV -  (NOAEL  x SSF x  ISF]  x
                                      WA +  (FA x  BAF)
 where:
 The terms are defined in appendix D, section n of the proposed Guidance except that:

 NOAEL = No Observed Adverse Effect Level in milligrams per kilogram body weight per
       day (mg/kg/d) determined for the taxonomic class to which the species requiring
       greater protection belongs.

 WtA = Average weight in kilograms (kg) of the species requiring greater protection.

 WA = Average daily volume of water consumed by the species requiring greater protection,
       in liters per day.

 FA = Average daily amount of food consumed by the species requiring greater protection, in
       kilograms per day (kg/d).

 BAF = Aquatic life bioaccumulation factor in liters per kilogram (L/kg) for the trophic
       level(s) at which the species requiring greater protection feeds. The BAF is chosen
       using guidelines for wildlife presented in appendix B, section V.B of the proposed
       Guidance.

 ISF = Intraspecies sensitivity factor.  An uncertainty factor to  account for differences in
       lexicological sensitivity among members of the population of the species requiring
       greater protection (may be 0.1 or less).

       The equation presented above for the calculation of a site-specific wildlife criterion
 for species requiring greater protection incorporates the use of  the NOAEL determined for
 the taxonomic class to which the species requiring greater protection belongs.  It is possible
 that the site-specific wildlife criterion may be based on  a species from a different taxonomic
 class than the wildlife value used to derive the State-wide wildlife criterion.  However, site-
 specific modifications may only be made when the site-specific wildlife criterion which
 results is more stringent man the State-wide wildlife criterion.  In addition, the above
 equation for the wildlife value includes an intraspecies sensitivity factor (ISF) to provide
 additional protection to individuals in a population since the proposed wildlife methodology is
 derived to protect wildlife populations, not individuals within the population.  Therefore,
 EPA highlights the use of site-specific modifications for the protection of individuals within a
population for species requiring greater protection for public comment.

       Section n.K of today's preamble states that EPA has initiated informal consultation
with the FWS to ensure that the requirements in part 132 are not likely  to cause jeopardy for

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threatened or endangered species in the Great Lakes System. EPA invites comments on
whether procedure 1 in appendix F to part 132 should contain specific text requiring
modification on a site-specific basis of aquatic life and wildlife criteria/values to provide
protection appropriate for threatened or endangered species.

       Individual Great Lakes States may make a decision to modify any aquatic life, human
health or wildlife criterion/value consistent with the requirements of this guidance.  Site-
specific modifications to criteria must  be submitted to EPA for approval or disapproval in
accordance with section 303(c) of the  Clean Water Act and 40 CFR 131.20. In addition, the
proposed Guidance would require that the State share information concerning site-specific
modifications to Great Lakes criteria/values with other Great Lakes States.  The State must
notify the other Great Lakes States at  the time a State proposes any site-specific modification
and supply a justification for any less  stringent site-specific modification. The State may
send a notice to the appropriate State agency designees and/or notify the EPA Region V
Clearinghouse to comply with this requirement.  The purpose of the notice is to allow other
Great Lakes States to comment on proposed site-specific modifications to criteria/values since
a primary objective of today's proposed Guidance is to provide consistency among the Great
Lakes States.

      EPA invites comment on two possible alternatives to the proposed procedure 1  of
appendix F. Under the first alternative, site-specific modifications as provided in procedure
1 would be available only for tributaries and connecting channels, not the open waters of the
Great Lakes. This first alternative was developed by the Technical Work Group, which felt
that the Great Lakes criteria provide appropriate protection for the open waters of the Great
Lakes and that  the proposed procedure 1 should only be  used for rather small localized areas
to provide  needed additional protection of specific subpopulations within those areas and, for
aquatic life, limited less stringent modifications.  The reason for the Work Group's proposal
was to ensure that a consistent set of requirements is applied throughout the open  waters of
the Great Lakes.

      Although EPA recognizes that  one of the goals expressed in the legislative history of
the Great Lakes Critical Programs Act of 1990 is to promote consistency in Great Lakes
water quality standards, EPA does not view this goal as overriding the authority specifically
reserved to States and Tribes in section 510 of the Clean Water Act to enact more stringent
requirements than necessary to implement  Clean Water Act requirements. Furthermore,
Article PV(a) of the Great Lakes Water Quality Agreement also clearly provides that the
Agreement is not intended to preclude adoption of more  stringent requirements.
Consequently, EPA is not authorized under the Clean Water Act to prohibit States from
adopting more stringent criteria/values for the open waters of the Great Lakes System.  For
these reasons, EPA is not proposing this first alternative  in today's proposed Guidance.
Nevertheless, EPA invites comment on this first alternative, and on EPA's interpretation of
the Clean Water Act.

      A second alternative would provide that the site-specific modification procedures in
procedure 1 of appendix F  would differ for pollutants that are not bioaccumulative chemicals
of concern (BCCs).  For non-BCCs, this alternative approach would  allow site-specific

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 modifications for human health and wildlife criteria/values that are either more stringent or
 less stringent than the criteria/values derived using the proposed Guidance methodologies,
 depending on local considerations (e.g., water quality characteristics). This alternative
 approach would provide additional flexibility to the States in conducting  site-specific
 modifications for non-BCCs.

       This second alternative was not viewed favorably by the Great Lakes Steering
 Committee.  EPA is proposing today that only those site-specific modifications which result
 in more stringent human health and wildlife criteria/values be allowed under the proposed
 Great Lakes Guidance, consistent with the Steering Committee proposal. However, EPA
 invites comment on this possible alternative approach.
D.  Additivity

1.  Introduction

       Traditionally, EPA has developed numerical criteria on a single pollutant basis.
However, many instances of contamination in surface waters involve mixtures of two or
more pollutants.  Such mixtures can interact in various ways which may affect the magnitude
and nature of risks or effects on human health, aquatic life and wildlife.  With respect to
impacts on aquatic life, the interactive effects of discharged pollutants on organisms is
ascertained through direct exposure of test organisms to a point source effluent in whole
effluent toxicity (WET) tests as described in procedure 6 of appendix F of the proposed
Guidance.  The use of such tests to determine additive pollutant effects on aquatic organisms
is a well-established component of existing Clean Water Act regulatory programs.  EPA
currently has no guidance regarding consideration of additive effects of pollutants on wildlife.

       EPA has considered mechanisms for assessing effects resulting from human exposure
to pollutant mixtures.  On September 24, 1986, the EPA published "Guidelines for the
Health Risk Assessment of Chemical Mixtures (51  FR 34014)," which is available in the
administrative record for this rulemaking.  These guidelines set forth principles and
procedures for human health risk assessment of chemical mixtures. Although the calculation
procedures in these guidelines differ for carcinogenic and non-carcinogenic effects, both
procedures assume dose additivity in the absence of information on specific  mixtures. Dose
additivity is based on the assumption that the components in a mixture have the same mode
of action and elicit the same types of effects. Because information on the interaction of
pollutants and on the modes of action  is so sparse,  EPA recommends in the 1986 guidelines
that risk assessments of mixtures be based on an assumption of additivity, as long as the
components elicit similar effects. Dose additivity could result in errors in risk estimates if
synergistic  or antagonistic interactions occur (i.e., additivity assumptions could result in
overestimates or underestimates of the actual risks).  Thus,  the assumption is not a "worst-
case" assumption, but a reasonable assumption within the bounds of possibility when specific
information on pollutant interaction is not available.
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       In an effort to address the concurrent human exposure to combinations of
carcinogens, three Great Lakes States (Illinois, Minnesota and Wisconsin) assume in criteria
development that the risk of a combination of carcinogens in a mixture is equal to the sum of
risks associated with exposure to each individual pollutant in the mixture. These three States
have adopted an acceptable cancer risk level of 10"s for exposures to individual pollutants. In
Minnesota and Wisconsin, the total risks associated with exposure to mixtures is not to
exceed 10"5 while Illinois allows a total cancer risk level of 104 for exposure to mixtures.

       The Great Lakes Water Quality Agreement addresses  this issue in Annex 12, which
states that "The Parties shall establish action levels to protect human health based on
multimedia exposure and the interactive effect of toxic substances."  In addition, Annex 12
of the Agreement recommends that research efforts on the interactive effects of residues of
toxic  substances on aquatic life, wildlife, and human health be intensified.  A supplement to
Annex 1 of the Agreement also provides for the development of specific objectives
addressing synergistic and additive effects of pollutants.

2.  Approaches Considered

       The Committees of the Initiative sought to develop a consistent approach  to additivity
within the Great Lakes States. Their deliberations resulted in proposals for the use  of
additivity for the protection of aquatic life, wildlife and human health. EPA evaluated the
Committees' proposals as well as other alternatives; both the Committees' proposals and
alternatives are discussed below.

       EPA's traditional approach is to address each pollutant on an individual basis in the
derivation of criteria and values.  However, EPA  has provided guidance in the past on how
to take additivity into account for the protection of aquatic life and human health. With
respect to the proposed Great Lakes Water Quality Guidance, EPA  invites comment on the
additivity-related issues discussed below and on whether a specific procedure, should be
either required or set fourth as a guidance in the final rule.

       a.  Aquatic Life. As proposed by the Committees of the Initiative, the proposed
Guidance accounts for additive effects on aquatic life through establishment of whole-effluent
toxicity (WET) limitations.  WET requirements are proposed under procedure 6  of appendix
F of the proposed Guidance.

       b.  Human Health - Carcinogens.  For carcinogenic effects on human health, the
1986 guidelines for mixture recommend that in the absence of contrary information  it be
assumed that the total cancer risk posed by a mixture of chemicals is the sum of risks posed
by exposures to individual chemicals. Since information on the interaction of pollutants in a
mixture is generally rather limited, the 1986 guidelines recommend the use of the additivity
assumption under most circumstances.  However,  the guidelines indicate a preference for
relying on actual data on the interaction of pollutants in mixtures whenever adequate data are
available. Therefore, EPA recommends that in those cases where it can be demonstrated that
the carcinogenic risks of a mixture are not additive, the additivity assumption should not be
used.

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       In its December 16, 1992, report, "Evaluation of the Guidance for the Great Lakes
 Water Quality Initiative," the EPA's Science Advisory Board (SAB) stated that additivity
 should not be used as a default, but rather multiple carcinogens should be considered on a
 case-by-case basis. This is because additivity assumes a common mechanism of action and
 carcinogens are known to act by a wide variety of mechanisms and to target different organs.
 The SAB report goes on to say that for compounds that act at the same receptor (such as
 dioxin, furans and PCBs) an assumption of additivity might well be defensible.  EPA invites
 comment on whether the assumption of additivity for carcinogens should be limited to those
 situations when adequate data are available on  the mechanisms of action.

    EPA invites comment on whether the narrative criteria of the States and Tribes providing
 that waters be free from substances that injure or are toxic to humans, animals or plants
 should be interpreted to account for the additive effects of chemicals. The purpose of this
 approach would be to prevent the total risk associated with carcinogens  in ambient waters
 from exceeding a non-appreciable level. As discussed elsewhere in the  proposed Guidance,
 EPA is proposing criteria/values for single pollutants based on a 10"5 cancer risk level.  EPA
 believes that the use of a risk level on total risk associated with chemical mixtures would
 enhance protection of human health, and consistency in addressing additive impacts
 throughout the  Great Lakes System.  It would also be consistent with the provisions of the
 Great Lakes Water Quality Agreement calling for consideration of the interactive effects of
 toxic substances.  Insofar as it may require greater reductions of pollutant discharges than
 would be required through implementation of individual chemical criteria alone, it would also
 further the "virtual elimination" goal of the Agreement.  EPA requests comments  on the
 possible use of 10"5 as a cap on the cancer risk associated with mixtures and on alternative
 risk levels (e.g., 10"*) that may be considered.  A specific option that would require
 interpretation of narrative criteria to establish a 10"5 cap on cancer risk associated  with
 chemical mixtures is set forth in  section 3 of this preamble discussion.

       EPA also requests comments on whether the additivity concept should be applied only
 to a limited (i.e., finite) number of the carcinogens in ambient waters that individually pose
 the greatest cancer risk to exposed populations rather than to all detected carcinogens.  For
 example, the narrative criteria could be interpreted such that the cumulative cancer risk posed
 by the presence of five (or some other number of) carcinogens in any given waterbody  or
 segment would  not exceed 10"5.  Such a modification would reflect the fact, recognized in
EPA's 1986 Guidelines for the Health Risk Assessment of Chemical Mixtures, that as the
number of pollutants covered by the additivity  assumption increases, the uncertainty
associated with the resulting risk assessment is also likely to increase. This approach could
also greatly ease the administrative burden of preparing total maximum daily loads (TMDLs)
and water quality-based effluent limits (WQBELs) based on the additivity assumption, since
it would provide a cut-off to what otherwise might be an extended inquiry and would relieve
regulatory authorities of the burden of identifying risks and sources associated with
carcinogens that pose a relatively insignificant risk to human health.  Finally, EPA requests
comments on whether a separate water quality  criterion (WQC) should be established for
carcinogenicity  (e.g., total cancer risk for ambient waters not to exceed  10**, 10~5, or some
other cancer risk level) rather than the approach discussed above for implementing narrative
criteria.

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       These alternatives differ considerably from the proposal of the Committees of the
Initiative with respect to considering additivity for carcinogens.  The Committees proposed
that the additivity assumption be applied only with respect to facilities otherwise requiring
WQBELs for individual carcinogens, and only as to those carcinogens requiring WQBELs.
Thus, the Committees did not propose application of the additivity assumption in setting or
interpreting ambient water quality criteria. Rather, their proposed approach would have
resulted in further limitations beyond WQBEL levels so that the carcinogens covered by
WQBELs from a given facility would not, after mixing with receiving waters, represent a
total cancer risk greater than  10"5.  Thus, the Committees' approach did not address
carcinogens for which WQBELs were not needed.  In addition, because not all sources
discharging a pollutant for which WQBELs are needed necessarily need WQBELs in order to
provide for attainment of water quality standards, not all sources discharging a given
carcinogen would have the additivity assumption applied to their discharges.

       Although EPA agrees  that the approach proposed by the Committees of the Initiative
offers certain administrative advantages as compared with other alternatives, EPA is
concerned that the Committees' approach could be inequitable in its application.  The full
text of the proposal of the Committees is reproduced below under section 4 of this preamble.
EPA invites comment on the possible use of that approach in the final rule to account for the
additive effects of carcinogens in the Great Lakes.

       c.  Human Health - Non-carcinogens. The 1986 EPA  guidelines on chemical mixtures
acknowledge that additivity of effects for non-carcinogens is most appropriate when
pollutants in a mixture elicit the same type of effect by the same mechanism of action.
However, because information on the mechanism of action is rather limited for many
pollutants, the 1986 EPA guidelines on chemical mixtures recommend that when two or more
compounds produce adverse effects on the same organ system (i.e.,  target organ) the effects
should be considered additive.  The 1986 guidelines additionally state that additivity for
dissimilar effects does not have strong scientific support. Thus, the underlying assumption in
the 1986 guidelines is that the components of a mixture which produces adverse effects on
the same target organ are additive.  This approach could overestimate or underestimate the
actual risks  due to possible antagonistic or synergistic interactions among  components in a
mixture.

       The  1986 guidelines recommend the use of a hazard index (HI) approach for non-
carcinogenic toxic agents. The hazard index indicates if there is a concern  with a mixture by
providing a rough measure of likely toxicity.  However, it does not define dose-response
relationships (i.e., its numerical value is not a direct estimate of risk).

       EPA solicits comment on the HI  approach for  applying additivity to non-carcinogenic
effects, as described in the 1986 guidelines.  This approach assumes that  multiple,
simultaneous exposures to a chemical could result in an adverse health  effect and that the
magnitude of the effect is proportional to the sum of the ratios of the actual exposures to
"acceptable" exposures.  When  the HI exceeds unity (i.e., 1) a potential for adverse health
effects exists.  While any single chemical with an exposure level greater than  the toxicity
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 value (i.e., threshold or Reference dose (RfD)) will cause the HI to exceed unity, for
 mixtures, the HI can also exceed unity even if no single chemical exceeds its RfD.

       The hazard index approach assumes dose addition for those compounds that induce
 the same target organ response and, therefore, a separate hazard index should be developed
 for each end point.  Dose addition (additivity) for dissimilar effects does not have strong
 scientific support.  For estimating the "HI" of a mixture of non-carcinogens based on
 additivity, the following equation may be applied:

                             HI = -JL+_£*_+ ...
                                  RfD,  RfD2
Where, for i =  1 through n:
       EJ = exposure level of the chemical in the mixture.
       RfD; = The Reference dose for that chemical.

       Since publication of the 1986 guidelines, EPA has published a "Technical Support
Document on Risk Assessment of Chemical Mixtures (November 1988)", which discusses the
hazard index approach as well as an alternative "toxicity equivalency factor" (TEF)
approach.  This  document is available in the administrative record for this rulemaking. The
"toxicity equivalency factor" approach was not discussed in the 1986 guidelines but has since
been recommended by EPA for risk assessment of certain chemical classes.  One advantage
of the TEF approach is that it allows the use of data to assess and quantify the toxicity of
mixtures that are not used to quantify the risk from exposure to single chemicals (i.e., acute
data, data from atypical routes of environmental exposure and in vitro data).  The 1988
Technical Support Document states that the TEF approach should be applied only to
compounds that  have the same mode of action or act independently.  The approach described
in the 1988 Technical Support Document is more restrictive than die 1986 guidelines in the
use of the additivity assumption for non-carcinogens but it is consistent with the proposal for
the use of TEFs made by the Committees of the Initiative. EPA also believes that the
approach in the  1988 Technical Support Document is not inconsistent with the original 1986
guidelines which state: "No  single approach can be recommended to risk assessments for
multiple chemical exposures."

      The preferred approach presented in the 1986 guidelines for conducting risk
assessment of mixtures is to use in vivo toxicity data on the mixture itself based on the route
of exposure and  duration period of concern.  However, this approach is not practical in most
cases because adequate toxicity data are available on very few complex mixtures.  The
"toxicity equivalency factor" approach involves estimating the potency of less well-studied
components in a mixture relative to the potency of better studied components, using data
from comparable types of in vitro and short-term in vivo assays.  So far, this approach has
been used only to estimate the toxicity of mixtures of chlorinated dioxins and dibenzofurans
by using extensive, data on the in vitro activity of these compounds. Today's proposal
requests comments on whether EPA should consider the "toxicity equivalency factor"
approach for these chemical classes and for any other mixtures for which TEFs may

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reasonably be calculated in the future as this area of research progresses and EPA is able to
develop additional TEFs.

       EPA specifically solicits comment on two possible approaches to addressing additivity
for non-carcinogens, set forth in sections 3 and 4 of this preamble. Both would require that
mixture of CDDs and CDFs be considered additive, in accordance with specific TEFs
described in more detail in section 2.d. of the preamble.  In addition, the option described in
section 3 would require use of bioaccumulation equivalency factors (BEFs) (discussed in
detail below) to account for differences in bioaccumulation potential of different CDDs and
CDFs.  The alternative set forth in section 3 would require generally that noncancer effects
be considered additive for those pollutants for which available scientific information supports
a reasonable assumption that the pollutants produce the same adverse effects through the
same mode of action, and for which TEFs and BEFs may reasonably be calculated.  Thus,
this option would establish a general requirement for States and Tribes to develop specific
additivity protocols for classes of pollutants when sufficiently supported by scientific
information.

       The second option which EPA specifically solicits comment on is set forth in section
4.  It would require application of additivity assumptions only for those pollutants for which
TEFs are set forth as part of the Great Lakes Guidance.  Pollutants covered initially would
include CDDs and CDFs, but more pollutants could be addressed through future revisions to
the rule. This option would best promote consistency among the Great Lakes States and
Tribes, but may involve more lag time between availability of scientific support for
application of additivity and use in  water quality management than would the option set forth
in section 3.

       d.   TEFs and BEFs for Chlorinated Dibenzo-p-dioxins (CDDs) and Chlorinated
Dibenzofurans (CDFs).  Chlorinated dibenzo-p-dioxins and dibenzofurans (CDDs/CDFs)
constitute a family of 210 structurally related chemical compounds. During the late 1970s
and early 1980s, EPA encountered  a number of incidents of environmental pollution in which
the toxic potential of CDDs and CDFs figured prominently. Initially, concern was focused
solely on 2,3,7,8-TCDD, which was produced as a low level by-product during the
manufacture of certain herbicides.

       During the past 20 years, many  studies have been conducted to elucidate the  toxic
effects of 2,3,7,8-TCDD. The data obtained from these studies are summarized in a number
of reviews (U.S. EPA, 1984; U.S. EPA, 1985; U.S. EPA, 1988; WHO, 1977; NRCC,
1981), which are  available in the administrative record for this rulemaking. EPA is currently
engaged in a major effort to generate more data on dioxin toxicity, and to update its analysis
of existing data.  While research efforts to date have not answered all of the questions,  the
data do show that 2,3,7,8-TCDD can produce a variety of toxic effects, including cancer and
reproductive effects in laboratory animals at very low doses.

       Data on the toxicity of other CDDs and for CDFs is considerably more limited.
These data are summarized in two EPA documents entitled "Interim Procedures for
Estimating Risks Associated  with Exposures to Mixtures of Chlorinated Dibenzo-p-Dioxins

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 and -Dibenzofurans (CDDs and CDFs)", (October 1986), and "1989 Update to the Interim
 Procedures for Estimating Risks Associated with Exposures to Mixtures of Chlorinated
 Dibenzo-p-Dioxins and-Dibenzofurans (CDDs and CDFs)", (March 1989) (the "1989 TEF
 Update"), which are available in the administrative record for this rulemaking.  While data
 available from long-term in vivo studies are limited for the majority of CDDs and CDFs, a
 much larger body of data is available on short-term in vivo studies and a variety of in vitro
 studies. These experiments cover a wide variety of end points; e.g., developmental toxicity,
 cell transformation, and enzyme induction (aryl hydrocarbon hydroxylase [AHH]). While the
 doses necessary to elicit the toxic response differ in each case, the relative potency of the
 different compounds compared to 2,3,7,8-TCDD is generally consistent from one end point
 to another.

       This information, developed by researchers in several laboratories around the world,
 reveals a strong structure-activity relationship between the chemical structure of a particular
 CDD or CDF congener and its ability to elicit a biological or toxic response in various in
 vivo and in vitro test systems.  (Bandiera et al., 1984; Olson et al., 1989;  U.S. EPA 1989;
 NATO/CCMS 1988a,b).  Research has also revealed a mechanistic basis for these
 observations. That is, a necessary (but not sufficient) condition for expression of much of
 the toxicity of a given CDD or CDF congener is its ability to bind with a particular protein
 receptor located in the cytoplasm of the  cell. This congener receptor complex then migrates
 to the nucleus of the cell, where it initiates reaction leading to expression of toxicity (Poland
 and Knutson, 1982).

       Based on this type of information, scientists suggested the development of numerical
 factors ("toxic equivalency factors" or "TEFs") that could be used to equate the toxicity
 posed by various CDDs and CDFs to 2,3,7,8-TCDD for purposes of conducting risk
 assessments including mixtures of the chemicals.  EPA developed an interim procedure that
 was reviewed and approved by EPA's Science Advisory Board,  and published as a
 monograph of EPA's Risk Assessment Forum in 1987.  The procedure was modified in
 certain respects in the 1989 TEF Update, and has been adopted  for international use by the
 North Atlantic Treaty Organization.

       EPA solicits comment on whether EPA  should require use of the specified TEF-based
 approach to equate mixtures of CDDs and CDFs to a concentration of  2,3,7,8-TCDD for
purposes of implementing the human health and wildlife criteria for 2,3,7,8-TCDD. Specific
 options are set forth in  sections 3 and 4  of this preamble.  The TEFs are the same as those
 set forth in EPA's 1989 TEF Update, and that Update provides the technical basis for the
proposal.  EPA also invites comment on whether other TEFs should be used rather than
 those listed in the 1989 TEF Update.

       The CDD/CDF TEFs address the toxicity of various chemicals  as compared to
2,3,7,8-TCDD, but do not address differences in bioaccumulation potential between the
 chemicals.  Because the criteria for 2,3,7,8-TCDD are largely driven by the relatively large
bioaccumulation factor for the chemical, and because available information suggests mat
other CDDs and CDFs  have different bioaccumulation factors, EPA believes that it may be
appropriate to use factors  accounting for the different BAFs in converting concentrations of

                                         57

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CDDs and CDFs to equivalent concentrations of 2,3,7,8-TCDD.  The option set forth in
section 3 incorporates this approach. The technical rationale for the particular
"bioaccumulation equivalency factors" (BEFs) selected is provided in a "Draft Technical
Support Document for Bioaccumulation Equivalency Factors," which is available in the
administrative record for this rulemaking.

       The Committees of the Initiative did not propose use of bioaccumulation equivalency
factors; their proposal would have assumed that BAFs for all CDDs and CDFs are identical
to that calculated for 2,3,7,8-TCDD.  Because available information on BAFs for other
CDDs and CDFs suggests that BAFs for those chemicals are generally smaller than for
2,3,7,8-TCDD, the Committee's proposal  would be a conservative, as well as a simplifying,
approach. EPA solicits comment on this option, set forth in section 4 of this preamble.

       e.  Wildlife.  As stated earlier, EPA has no present policy on the use of additivity for
wildlife effects.  EPA solicits comment, however, on whether additivity with respect to
wildlife effects should be treated in a manner consistent with the options described above for
noncancer human health effects and for mixtures of CDDs and CDFs. EPA believes that an
argument can be made that the TEFs for CDDs and CDFs developed for use in human health
risk assessments should generally be applicable to wildlife, since the TEFs are based largely
on animal studies.  Using the TEF approach, the total allowed exposure level for mixtures of
these congeners would not exceed the level established by the wildlife criteria for 2,3,7,8-
TCDD, based on 2,3,7,8-TCDD equivalents. Two specific alternatives regarding application
of additivity principles to wildlife effects are set forth in sections 3 and 4 of this preamble.
EPA requests comment on these options, and on possible alternatives to them.

       In developing this proposed Guidance, the use of TEFs for polychlorinated biphenyls
(PCB) congeners for wildlife was considered.  In December 1990, EPA's Risk Assessment
Forum held a workshop  to specifically address the use of TEFs for PCBs (Risk Assessment
Forum, Workshop Report on Toxicity Equivalency Factors for Polychlorinated Biphenyl
Congeners, June 1991, EPA/625/3-91-020). This workshop concluded that the application of
TEFs to PCBs is not as straightforward as it is in the case of CDDs and CDFs, but that
TEFs for dioxin-like PCB congeners are feasible and may be considered additive with those
for CDDs and CDFs. Further, the workshop concluded that current dioxin-like TEFs appear
to be useful in assessing traditional measures of wildlife toxicity.  The workshop, however,
recommended that a TEF scheme for PCBs should be seen as an interim procedure and
promising bioassay approaches should also be vigorously pursued.

       On March 19-20, 1992, a Dioxin Ecotox Subcommittee of the Ecological Processes
and Effects Committee of the Science Advisory Board met to review EPA's research
proposals to support the development of an ambient aquatic life water quality criterion for
2,3,7,8-TCDD.  At that meeting, the Subcommittee addressed the general issue of research
needed to support the use of TEFs for aquatic life and wildlife. In their final report dated
August 1992, the Committee stated that the TEF approach appears promising for aquatic life
and wildlife but more studies are needed to show phylogenetic variability.  The Committee
concluded that at the present time there are insufficient data available to judge the reliability
and the accuracy of the TEF approach.

                                         58

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       A recent study of the potencies of CDDs, CDFs and PCBs relative to 2,3,7,8-TCDD
for producing early life stage mortality in rainbow trout calculated TEFs for each of these
classes of chemicals (Walker and Peterson, 1991). The TEFs calculated in this study for
CDDs and CDFs were similar to those proposed by Safe (1990).  However, the TEFs for the
PCS congeners were 14 to 80 times less than those proposed in Safe (1990). The results of
the Walker and Peterson study illustrate the significant uncertainties in applying TEFs across
species and endpoints for PCB congeners.  Further, another recent study concluded that the
TEFs proposed in Safe  (1990) for the "dioxin-like" PCBs overestimate the potency of these
compounds by a factor of 10-1,000 (DeVito et ah, 1992).

      EPA solicits comments on whether TEFs for PCBs should be included together with
those for CDDs and CDFs in the use of the additivity concept for wildlife effects. Table
Vm.D-1 presents TEFs for PCB congeners from Safe, 1990.  EPA specifically requests
comment on the inclusion of these TEFs for wildlife in the Great Lakes Guidance.
Table Vm.D-1
Toxic Equivalency Factor Values for PCBs

                          IUPAC #                 TEF Value

(a) Coplanar PCBs
3,3',4,4',5-PeCB          126                      0.1
3,3',4,4',5,5'-HxCB       169                      0.05
3,3',4,4'-TCB             77                       0.01

(b)Monoortho Coplanar PCBs
2,3,3',4,4'-PeCB          105                      0.001
2,3,4,4'-PeCB             114                      0.001
2',3,4,4',5-PeCB          123                      0.001
2,3',4,4',5-PeCB          118                      0.001
2,3,3',4,4',5-HxCB        156                      0.001
2,3,3',4,4',5-HxCB        157                      0.001
2,3',4,4',5,5'-HxCB       167                      0.001
2,3,3',4,4',5,5'-HpCB      189                      0.001
                                         59

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3.  Request for Comment on Approach Considered for Implementing the States' Narrative
Criteria

       The text presented below represents one approach that would specify that the narrative
criteria be interpreted to account for the additive effects of chemicals.  EPA requests
comments on whether the language below should be added to the Implementation Procedures
of the final Guidance.

       The following procedures establish the manner in which the additive effects of
chemical mixtures shall be treated when interpreting the narrative criteria of the States and
Tribes requiring that all waters be free from substances that injure or are toxic or produce
adverse physiological responses in humans, animals or plants.

       A.  Aquatic Life Effects.  Whole-effluent toxicity requirements established under
procedure 6 of appendix F of part  132 shall be used to account for additive effects to aquatic
organisms.

       B.  Wildlife Effects.  The effects of individual pollutants shall be considered additive
for chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans, and for other pollutants for
which available scientific information supports a reasonable assumption that the pollutants
produce the same adverse effects through the same mechanism of action, and for which toxic
equivalency factors and bioaccumulation equivalency factors may reasonably be calculated.
For chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans, additivity shall be
accounted for in accordance with section E.  For other pollutants, toxic equivalency factors
and bioaccumulation equivalency factors shall be developed and thereafter applied in a
manner similar to that described in section E based either on a relationship to 2,3,7,8-TCDD
or to  some other chemical, as appropriate.

       C.  Human Health - Non-cancer Effects.  The effects of individual pollutants shall be
 considered additive for chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans, and for
other pollutants for which available scientific information supports a reasonable assumption
that the pollutants produce the same adverse effects through the same mechanism of action,
and for which toxic equivalency factors and bioaccumulation equivalency factors may
reasonably be calculated.  For chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans,
additivity shall be accounted for in accordance with section E.  For other pollutants, toxic
equivalency factors and bioaccumulation equivalency factors shall be developed and thereafter
applied in a manner similar to that described in section E based either on a relationship to
2,3,7,8-TCDD or to some other chemical, as appropriate.

       D.  Human Health -  Cancer Effects.  The incremental cancer risk of each carcinogen
 shall be considered to be additive  and the total cancer risk shall not exceed 10"5.  However,
the State or Tribe may determine, based on information submitted by a permittee or
otherwise available to the State or Tribe, that the carcinogenic risk for a given mixture is not
additive.
                                           60

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       E.  Toxicity Equivalency Factors.  The following TEFs shall be used when
implementing human health or wildlife criteria for 2,3,7,8-TCDD. The concentration of
each CDD and CDF in an effluent shall be converted to a 2,3,7,8-TCDD equivalent
concentration by multiplying the concentration of the CDD or CDF by the TEF shown in
Table Vffl.D.2 below, and multiplying that product by the bioaccumulation equivalency
factor in Table vm.D.3 below.  All resultant concentrations shall be added to produce an
equivalent 2,3,7,8-TCDD concentration. The equivalent 2,3,7,8-TCDD concentration shall
be used to establish TMDLs (including wasteload and load allocations) pursuant to procedure
3. This equivalent 2,3,7,8-TCDD concentration shall also be used as the concentration of
2,3,7,8-TCDD for purposes of assessing the total cancer risk of carcinogens pursuant to
section 4.D.
Table Vffl.D-2
Toxic Equivalency Factor Values for CDDs and CDFs

Congener	TEF

2,3,7,8-TCDD                                     1.0
1,2,3,7,8-PeCDD                                   0.5
1,2,3,4,7,8-HxCDD                                0.1
1,2,3,6,7,8-HxCDD                                0.1
1,2,3,7,8,9-HxCDD                                0.1
1,2,3,4,6,7,8-HpCDD                               0.01
OCDD                                            0.0001
2,3,7,8-TCDF                                     0.1
1,2,3,7,8-PeCDF                                   0.05
2,3,4,7,8-PeCDF                                   0.5
1,2,3,4,7,8-HxCDF                                 0.1
1,2,3,6,7,8-HxCDF                                 0.1
2,3,4,6,7,8-HxCDF                                 0.1
1,2,3,7,8,9-HxCDF                                 0.1
1,2,3,4,6,7,8-HpCDF                               0.01
1,2,3,4,7,8,9-HpCDF                               0.01
OCDF                                            0.001
                                       61

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Table Vm.D-3
Bioaccumulation Equivalency Factors (BEFs)
Congener	TCDD BEF	

2,3,7,8-TCDD                                     1.0
1,2,3,7,8-PeCD                                    £0.8
1,2,3,4,7,8-HxCDD                                <0.3
1,2,3,6,7,8-HxCDD                                £0.2
1,2,3,7,8,9-HxCDD                                £0.2
1,2,3,4,6,7,8-HpCDD                               £0.03
OCDD                                            £0.02
2,3,7,8-TCDF                                     1.2
1,2,3,7,8-PeCDF                                   0.3
2,3,4,7,8-PeCDF                                   1.8
1,2,3,4,7,8-HxCDF                                £0.3
1,2,3,6,7,8-HxCDF                                £0.3
2,3,4,6,7,8-HxCDF                                £0.5
1,2,3,7,8,9-HxCDF                                £0.5
1,2,3,4,6,7,8-HpCDF                               £0.003
1,2,3,4,7,8,9-HpCDF                                £0.1
OCDF                                            £0.005

Notes:
1. *BEF x rc^AF = "BAP
2. *BAF = lipid-based bioaccumulation factor for total congener concentration
      in water.
       The TEFs provided in Table VHI.D-2 are the same as those set forth in EPA's 1989
TEF Update.  However, this Table has been reorganized to make it consistent with Table
VTQ.D-3 above (which lists the BEFs for specific congeners and does not include CDDs and
CDFs with TEF values of zero).

4. Request for Comment on Alternative Approach

       The text presented below represents the proposal for additivity of the Committees of
the Initiative, modified by EPA to delete the application of TEFs for PCBs to wildlife.  EPA
requests comments on whether the language below should be added to the implementation
procedures of the final Guidance.

       The toxic action of some pollutants in mixtures is additive in their effects on
organisms. The following procedure establishes the manner in which the additive effects of
chemical mixtures shall be treated. This provision shall be applied to point source discharges.
                                        62

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       A. Aquatic Life Effects.  Whole-effluent toxicity requirements established under
 procedure 6 of appendix F of part 132 shall be used to account for additive effects to aquatic
 organisms.

       B. Wildlife Effects.  When establishing wasteload allocations (WLAs) for the
 protection of wildlife, the effects of individual pollutants shall be considered additive for the
 pollutants for which toxicity equivalency factors (TEFs), as provided in section E of this
 procedure, are available.

       C. Human Health - Non-cancer Effects.  When establishing wasteload allocations
 (WLAs) for the protection of human health for non-carcinogens, the effects of individual
 pollutants shall be considered additive for the pollutants for which toxicity equivalency
 factors, as provided in part F of this procedure, are available.

       D. Human Health - Cancer Effects.  When establishing wasteload allocations
 (WLAs) for the protection of human health for carcinogens, the following shall apply:

       (1) Except as noted in (2) below, in cases where an effluent contains detected levels
 of more than one pollutant for which a Tier I criterion or Tier n value exists and for which
 a water quality-based limitation is required under Procedure 5, the incremental risk of each
 carcinogen shall be considered to be additive and the total cancer risk shall not exceed
 The wasteload allocation (WLA) for each carcinogen  shall be established in a permit to
 protect against potential additive  effects associated with simultaneous,  multiple-chemical
 human exposure such that the following condition is met:
Where:
Cj...n = the monthly average effluent limitation expressed as concentration of each separate
carcinogen in the effluent.

WLA,...n = the wasteload allocation concentration calculated for each substance at each
permitted facility independent of other carcinogens that may be present in the receiving
waters based on the human cancer criterion for each respective carcinogen.

(2) If the permitting authority determines, based on information submitted by the permittee,
that the carcinogenic risk for a mixture is not additive, the permitting authority may establish
wasteload based on that information.

       E.  TEFs applied to Wildlife Effects.  The permitting authority shall use toxicity
equivalency factors when establishing wasteload allocations for the protection of wildlife for
chlorinated dibenzodioxins (CDDs) and chlorinated dibenzofurans (CDFs). The
concentration of each CDD and CDF in an effluent shall be converted to a 2,3,7,8-TCDD
equivalent concentration by multiplying the concentration of the CDD or CDF by the TEF
shown in Table Vffl.D.4.  All resultant concentrations shall be added to produce an

                                          63

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equivalent 2,3,7,8-TCDD concentration. The equivalent 2,3,7,8-TCDD concentration shall
be used to establish a wasteload allocation consistent with procedure 3.  Whenever one or
more CDDs and/or CDFs are present in an effluent, the permitting authority shall establish a
wasteload allocation for 2,3,7,8-TCDD. The permittee shall be considered in compliance
only if the sum of the effluent concentration times the TEF for all the CDDs and CDFs are
less or equal to the wasteload allocation for 2,3,7,8-TCDD.  If there are carcinogens other
than CDDs and CDFs in the effluent, the sum calculated for the equivalent 2,3,7,8-TCDD
concentration must be used in the formula in D(l) above for C*, where k represents 2,3,7,8-
TCDD.

       F. TEFs applied to Human Health - Cancer Effects.  The permitting authority shall
use toxicity equivalency factors when establishing wasteload allocations for human health-
based criteria for CDDs and CDFs.  The concentration of each CDD and CDF in an effluent
shall be converted to a 2,3,7,8-TCDD equivalent concentration by multiplying the
concentration of the CDD or CDF by the TEF shown in Table Vm.D.4. All resultant
concentrations shall be added to produce an equivalent 2,3,7,8-TCDD concentration.  The
equivalent 2,3,7,8-TCDD concentration shall be used to establish a wasteload allocation
consistent with procedure 3.  Whenever one or more CDDs and/or CDFs are present in an
effluent, the permitting authority shall establish a wasteload allocation for 2,3,7,8-TCDD.
The permittee shall be considered in compliance only if the sum of the effluent concentration
times the TEF for all the CDDs and CDFs are less or equal to the wasteload allocation for
2,3,7,8-TCDD.  If there are carcinogens other than CDDs and CDFs in the effluent, the  sum
calculated for the equivalent 2,3,7,8-TCDD concentration must be used in the formula in
D(l) above for Q, where k represents 2,3,7,8-TCDD.
                                        64

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 Table Vffl.D-4
 Toxic Equivalency Factor Values for CDDs and CDFs
 Compound
Tef Value
 1.  Dioxins
 Mono-, Di-, and TriCDDs
 2,3,7,8-TCDD
 other TCDDs
 2,3,7,8,-PeCDD
 other PeCDDs
 2,3,7,8-HxCDDs
 other HxCDDs
 2,3,7,8-HpCDD
 other HpCDDs
 OCDD

 2. Furans
 Mono-, Di-, and TriCFDs
 2,3,7,8-TCDF
 other TCDFs
 2,3,4,7,8-PeCDF
 1,2,3,7,8-PeCDF
 other PeCDFs
 2,3,7,8-HxCDFs
 other HxCDFs
 2,3,7,8-HpCDFs
 other HpCDFs
 OCDF	
0
1
0
0.5
0.0
0.1
0.0
0.01
 0.0
0.001
0
0.1
0.0
0.5
0.05
0.0
0.1
0.0
0.01
0.0
o.oor
5. Request for Comments

      EPA requests comment on each element of the text for the two approaches to
additivity presented in sections 3 and 4 above, including all subjects and issues raised in the
preamble discussion whether or not specific regulatory text has been provided in the
proposed Guidance, and any suggested alternative requirements or combinations of
requirements to address these elements and issues in the final rule. EPA may promulgate
final rules based on any of the issues or subjects  discussed in this preamble or based on a
combination of possible requirements to address these subjects and issues.
                                       65

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CHAPTERS
       Portions  of Appendix F to Part 132—Great Lakes  Water
Quality Initiative  Implementation Procedures

Procedure 1: Site-specific Modifications to Criteria/Values

       A. Requirements for Site-specific Modifications to Criteria/Values
Criteria or values may be modified on a site-specific basis to reflect local environmental
conditions as restricted by the following provisions. Any such modifications must be:
protective of designated uses and aquatic life, wildlife and human health; and submitted to
EPA for approval/disapproval.  Li addition, any  site-specific modifications that result in less
stringent criteria must be based on sound scientific rationale.

       1.  Aquatic Life.  Aquatic life criteria or values may be modified on a site-specific
basis to provide an additional level of protection, pursuant to authority reserved to the States
and Tribes under Clean Water Act section 510.

       a. Less stringent site-specific modifications to chronic or acute aquatic life criteria or
values may be developed when:

       i. The local water quality parameters such as pH, hardness, temperature, color, etc.,
alter the biological availability and/or toxicity of a pollutant; and/or

       ii.  The sensitivity of the local aquatic organisms  (i.e., those that would live in the
water absent man-induced pollution) differs significantly  from the species actually tested in
developing the criteria.

       Guidance on developing site-specific criteria in these instances is provided in Chapter
4 of the U.S. EPA Water Quality Standards Handbook.

       b.  Less stringent modifications also may be developed to the chronic aquatic life
criteria or values to reflect local physical and hydrological conditions.

       2.  Wildlife.  Wildlife criteria or values may be modified on a site-specific basis to
provide an additional level of protection, pursuant to authority reserved to the States and
Tribes under Clean Water Act section 510. This may be accomplished through the use of an
additional uncertainty or other documented factor in the equation for the Wildlife Value.

       3.  Bioaccumulation.  Bioaccumulation factors may be modified on a site-specific
basis to larger values than derived pursuant to authority reserved to the States and Tribes
under Clean Water Act section 510. Bioaccumulation factors shall be modified on a site-
specific basis where  reliable data shows that local bioaccumulation is greater than the system-
wide value.
                                         66

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       4. Human Health.  Human health criteria or values may be modified on a site-
 specific basis to provide an additional level of protection, pursuant to authority reserved to
 the States and Tribes under Clean Water Act section 510.  Human health criteria or values
 shall be modified on a site-specific basis to provide additional protection appropriate for
 highly exposed subpopulations.

       B.  Notification Requirements.  When a State proposes a site-specific modification to
 a criterion or value as allowed in section A above, the State shall notify the other Great
 Lakes States of such a proposal and, for less stringent criteria, supply appropriate
justification.

       C. References. U.S. EPA.  1983. Water Quality Standards Handbook. Chapter 4.
 U.S. Environmental Protection Agency, Office of Water Resource Center (RC-4100), 401 M
 Street, S.W., Washington, D.C. 20460.

 Procedure 4: Additivity

       [Reserved]
                                         67

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          APPENDIX A:








     INTRODUCTORY MATERIAL



   AND OUTLINE FROM PREAMBLE



        TO GREAT LAKES



WATER QUALITY GUIDANCE PACKAGE
               in



58 Federal Register 20802-21047



    Friday, April  16,  1993



    40 CFR parts 122 et al.

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20802
                Federal Register / Vol. 58. No. 72 / Friday.  April 16. 1993 / Proposed Rules
ENVIRONMENTAL PROTECTION
AGENCY

40 CFR Parts 122,123,131, and 132

[FRL 4205-61

RJN2040-AC08

Proposed Water Quality Guidance for
the Great Lakes System

AGENCY: U.S. Environmental Protection
Agency.
ACTION: Proposed rule.

SUMMARY: This document provides
opportunity for comment on the
proposed Water Quality Guidance for
the Great Lakes System ("Guidance")
developed under section 118(c)(2) of the
Clean Water Act (CWA). as amended by
section 101 of the Great Lakes Critical
Programs Act of 1990 (CPA). This
Guidance, once finalized, will
minimum water quality standards,
antidegndation policies,mni*
implementation procedures for waters
within the Great Lakes System in the
States of New York. Pennsylvania. Ohio.
Indiana. Illinois. Minnesota. Wisconsin,
                    mg the waters
within the jurisdiction of Indian tribes.
Today's proposal also is intended to
satisfy the requirements of section
118(c){7)(C) of the dean Water Act that
EPA p"h|t«h 
-------
                Federal Register  / Vol 58. No. 72  / Friday. April 16. 1993  /  Proposed Rules
                                                                                                               20803
  c. Sums of Negotiations With Canada on
    Revising tne Specific Objectives
C Governors' Toxics Agreement

D. Great Lakes Water Quality Initiative
l Formation of Great Lakes Water Quality
    uuua&ve
2. Great Lues Critical Pragnms Act of 1990
3. Process After the CPA
E Elemeno of the Guidance
1 Water Quality Criteria for the Protection of
    Aquatic Life
2 Water Quality Criteria far the Protection of
    Human Health
3 Wat* Quality Criteria for the Protection of
    Wildlife
4. ff"*Tif'ii'f"**¥ttT*Ti Facton
5. AntifwaraflatioTi
6. Implementation Procedures
F. Science Advisory Board Review

G. Other Protrams to Protect and Reeton the
Great Laos
1. Gnat Lakes Five Year Strategy
2. Gnat Lake* Foliation Prevention Actiae
    Plan
3. Lakewide 1 lanagamenrt Fteaa (LaMPi)
4. Remedial Action Flaw PtAP»
1 frtilMiiiiaeail lieillniaiili
6. AaMapawfc Depoattioa
7. Storm Water
ft. Combmed Saver Overflows (CSOa)
9. Dtschejgae of Oil and Handout Poibtiai
10. NflBpoiBi Soim?M CBT PQUBDJOB
11. Gn« Lakes Fish AcMaoriM
12.1
13. Gnat Lakes Toxic
H. References
A. Scope and Purpose


C Adoption of Criteria, Methodologies, and


D. Application of Methodologies. Polids*.
 1. The Two-Ttand Approach
 2. Application of Tier II
 3. Application ofTia
 E. Applicability of the Water Quality
 Uiioanca
 1. Criteria and Values
 F. Excluded Pollutants

 G. Pollutants of Initial Focus for Criteria
 Development, and Bioaccumulative
 Chemicali of Concern
 H. Adoption Procedures

 I. Interpreuuon of "Consistent With"

 ). Precedential Effect of Elements of the
•Guidance

 JC Endangered Species Act

 L. Request for Comments

 m. Aquatic Life
 A. Introduction and Purpose

 B. Tier I Criteria

 2. Selection of PoUntanta for Application of
     Tier 1 Criteria. Methodology
 3. Tier I Numeric Criteria
 4. Potential Change* to National Guidelines
 CTiernVa
   b. Applicability of the topoMd Guidaoce
   c. h.irtlftratmB for the Propoeed Approach
   d. Other Options Cousidcnd
 2.inrpitnntttioaPn
                                                                                  b.ADE
                                                                                  C.DUS
                                                                                5. Exposure Assumptions
                                                                                  a. Body Weunt
                                                                                  b. Duration of Exposure
                                                                                  c. Incidental Exposure
                                                                                  a. rvinirmg Water Cossumpuoc
                                                                                  e. Fish O"1 •""option
                                                                                  f- Fifttrn?""*'******* *?««^"f (PAF)
                                                                                  g. Relative Source Contribution
                                        Gnat Lake* watatQaeiHy Agresniein mil
                                        Gnat Lite Qtttaai Fwsjnms Ad of 1990
                                        1. Tlat 1 Aqattk Uh Qttstm ad
                                        2, Tier D
                                          a,
                                          b.
                                        JV.l
                                                      WMh the dean Water Act
                                                       WttB the Gnat Lakae
                             Water Act
                 Wttk the Gnat Ukw
   a. Appiicabllrty of the Proposed Guidance
   b. Justification for the Propoeed Approach
   LWet-wseiherltoiittSoQraeDischjDgM
   iL ExcAtded Polhttasts
                                            EPA
                                         •. AdoptioB of Wat* QemlUjr
                                         V.HumaaHfahh
                                         A. Introduction
                                         B. Critaria Methodologies
                                         1. Endoouts Addressed by thi* Human
                                             Health Methodologies
                                         2. Macbmsm of A
                                           a. Cancer

                                          3.ChotteoflUskUvel
                                          4. Acceptable Dose
                                           a. RAD
                                                                                6. Minimum
                                                                                    TiarD
                                                                                  a. Carcinogens
                                                                                  b. NontV^ f^^^^A • ^iV^^ latf «A^^
    uonsooDejsci mn IBS wws Luav water
    Quality AenseBiejt
E.lteTiewoftttfGreatUkeiatUanoebytDe
EPA Science Advisory Board (SAB)

F.Utantamt

VLWdlifi
                                                                                     Animal
                                                                                                 Wild i
                         i for BAFs
                         I BAFs
    b.StaadsfldUnidVahMe
    L Standard Lipid Vain* for Homta Health
     BAFs
    IL Standard UpidVabe far WUolife BAFs
    11LI
    c. Food Chain MuhrpUs
    dEftsct of Metabolism on BAFs
    e. Biotvathttlttv
    f. Other Uees of BAFs
  4. SAB I
  5. Rail
                                                                                  3. The Gnat Lake* Water Quality Initiative
                                                                                     WUdlifs Critsni MetboaokfT
                                                                                    a. Panmctan of the Hexard Compooant of
                                                                                     tbe GLWQI WUdhii Critaria
                                                                                    L LOAEL to NQAEL Bxrnpoktions
                                                                                    iiL Species SeMTthrtty Fmctor
                                                                                    iv.lntmpecieeVariaWltty
                                                                                    v. AUeiiiau*e Formula for Haxard
                                             LAppnacfaUaedto
                                               Spec^Identtfledforl

                                             iii. Exposun Bootes Considered
                                           C Additional I

                                           1. UM OI HVDDil& HMnA Ptf«MlfBl
                                               Denva&on
                                            3. Acceptable Endnoma for Toaddty Studies
                                            4. Use of an Acute to Cbronic Conversion
                                               Ratio
                                                          A-2

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20804
  Federal Register  /  Vol. 58, No. 72  /  Friday, April is. 1993  /  Proposed Rules
0. Chemical Selection for Wildlife Criteria
Derivation

£. Tier I Wildlife Criteria and Tier 0 Wildlife
Values

F. Companion With the CWA and
Relationship to National Guidanc*
l. Relationship to E»*m"B National Guidance
2. Relationship to Current Efforts to Provide
    National Guidance for the .Development
    of Wildlife Criteria
G. Comparison of Wildlife Criteria and
Methods to National Program and to Gnat .
Lake* Water Quality Agreement
1. "No Lees Restrictive" Than the CWA and
2. Confonnance With the Gnat Lakes Water
    Quality Agreement
H. Bibliognpby

Vu. A tttttntffWiOttftfi
A. General Discussion/Background
t. Federal Antideandation Policy and
    History
  a. History of the Federal Antidegndanon
    Policy
  b. Existing National Antidegndation Policy
  cCnttLakeaStatae Experience
  dAlls«natrn Approaches to A Meeting
    Lowering of Water Quality
B. Geaenl Outline of GLWCJ
                           h. Relationship of EEQ to Implementation
                             Procedure 8
                         E. Oe Minimis Lowering of Water Quality
                         1. Background
                         2. Detailed Description of De Minimis Test
                           a. Specific Tests Included in De Mimims
                             Deffloostnbon
                           b.£xamples
                           i. Example 1
                           il. Example 2
                           iii. Example 3
                         3. Issue*
                           a. Use of Assimilative Capacity in De
                             Miaimis Decision
                           b. Fixing Assimilative Capacity at a Date
                             Certain and Choice of Date
                           c. Demonstntion That No Ambient Change
                             Occurs  as a Result of Increased Loading
                           d Use of the Margin of Safety Specified in
                             the Implementation Procedures as a
                           e. Multiple De Miaimis Lowering of Water
                             Quality by a Single Source
                         F. Antidegndation Demoastntioo
                         l.Backi
                                                  id and R
                         2. Hienochy of Antidegndation
                             Demonstntions
                         3. Mentifiration of Prudent tad Feasible
                             Pollution PnnaUua Atternatiree to
                             Proven* or Reduce the Signif
                             Lowering of Water Quality
                           a-SobatitntioaofBCCswithNoB.
H. Offsets
I. Inoorpontion Into State Water Quality
Standards
VUl. General Implementation Procedures
A. Site-Specific Modifications to CTitena

B. Variances From Water Quahtv Standarcs
for Point Sources
1. Current EPA Policy
2. GLWQ1 Proposal (40 CFR part 132.
    Appendix F, Procedure 2)
3. Applicability
4. Maximum Timefreme
5. Conditions to Gnnt a Variance
6. Timeinme to Submit Application
7. Public Notice of Preliminary Decision
8. Final Decision on Variance Request
9. Incorporating State- or Tribal-approved
    Variance Into Permit
10. Renewal of Variance
11. EPA Approval
12. State or Tribal Water Quality Standards
    Revisions
13. Consietency With the CWA and
    finnflnreitnne With the GLWQA
  a-Consistency With the Clean Water Act
  li Puiii	• Tiriih llii Piiai I it ii
    Water Quality Agnement
14. Gjrtto Considered

C Total Mexmwm Daily Loads
                              of

                anAntio^egndation
  a. BetaMshTnat the Action May
    SigulAtuuy Lower Wetar Quality
  b. GbancMrisD toe Receiving Water
C Activities Covered by the Great Lakes
                                          b. Appttceiion of Water Conservation
                                            Method*
                                          e. Weete Sown Reductions Within Procest
                           d-IUcyi
                                                         of Waste By
                             Either Liquid. Solid, or Gaseous
1.
   Outstanding National Reeouroe Waten.
   and Other H	of Waten
  a. fixieting Federal Policy
  D.GLWQI Guidance
2, Significant Lowering of Water Quality
3. Coven All Pollutants Soureet (Poiat aad
       ihQualitvWatan    4. Ali«nMtr»» or Enhanced Tnatment
                                            Atenstivee That Eliminate the
                                            Sigirtflnem Lowering of Water Quality
                                        S. Social or Economic Development
 5. Discharges of FU1 Material in Wetlands
 D. Existing Effluent Quality
                                          b. Net Positive bapect
                                          c Other Developments
                                        6. Special Remedial Action Provision
                                        7.
 2. Options far EEQ Controls
   a. Option L-EBQ as Numeric Mass Loading
                            a. Other Options Considered far
                              Determining if Significant Lowering of
                              Wegr Quality is Neceesary
                            b. Rfjniimuic Recmety
                            t Beet Available Technology
     to
 to Options lor 2
   %f THf^haWM
EEQ
   a. Puniahment of Good Perfannen
   b. Statistical Procedures
   c Dan Availability and Repneentativeness
   d ApplasatioB to MunicipaUties
   a. Reetrictions on Actions Venus
     Limitations en Pollutants
   t Statutory Authority far EEQ
   g. Ability to Accommodate a Return to
     Increaeid Production Levels Under
                                            AgMbut the Significant Lowering of
                                            Water Quality
                                        G. Special Antiojegradatioa Provisions far
                                        LakeSoperior
                          Z.Efiect
                            a. Relationship to Other Antidegndation
                              National Reeoune Waten
                            c. l^ki Superior Biaaacamulative
                              Substances of Immediate Concer
                                                                                                    to TMDL
                                                                            TMDLs
  b.
  c
  dPolbmuttTcinsport
 3. Development of the Proposed Guidance
  a. The Proposed Guidance
  b. Overview of Option A and Option B
 4. General ^'it******^** of Application
  a. General Condition 1
                                                                    c. General Condition 3
                                                                    d General Condition 4
                                                                                  f ff
                                                                                            JWHlMftff y
                                                                    t rif
                                                                                  {.General Condition 10
                                                                                  k. General Condition 11
                                                                                5. Special Provisions for BGCi
                                                                                  a. Reason far Restricting Disch
                                                                                  cNewSoutoes
                                                                                         g
                                                                                                             rge of BCCs
                                                                                                     g the Ten Year
                                                                                    PhaeeOut
                                                                                   e. Exception to the Tea Year Phase Out of
 6. TMDLa far Open Waten of the Great Lakes
   a. Point Source Mixing Zones far Chronic
     Criteria and Values
               I^KJ Allpcationi
                  kAcuta Effects
                                                                    c Protection
                                                                                  dProcadune When High Background
                                                                                    ComamUal ions an Present
                                                                                  e. Margin of Safety
                                                                                  L Chronic Criteria and Values
                                                                                  iL Aeote Criteria and Values
                                                                                 7. TMDLs far Discharge* to Tributaries
                                                                                  a. Steady State Maas Balance Approach
                                                                                    Common to Both Options
                                                         A-3

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                 Federal Register / Vol.  58. No. 72  / Friday.  April  16. 1993 / Proposed Rules
                                                                                                                  20805
  b. Design Fiows Common to Both Options
  c. Overview of Option A
  i. Load Inventory
  ii. Loading Capacity
  iii. Basin Margin of Safety
  iv. Load Reduction Targets
  v. Basis Allocations
  vj. Site-specific Cross-checks
  vii. Establish Final Allocations
  viii. Monitoring Provisions
  d. Overview of Option B
  i. Source-specific TMDLs
  ii. Mixing Zone Capacity
  iii Background Loadings
  iv. Formula Modification Baaed on Mixing
   Zone Studies
  v. Limitation of Use of Source-specific
   TMDL Formula
  e. Pollutant Degradation
8. Pollution Trading Opportunities
9. State Adoption
10. Summary of Other Options Considered
11* Request for Comments
D.Additrvtty
1. IttlfDOUCtiOP
2. Approaches Considered
  a. Aquatic Ufc
  b. Hunan Health-Carcinogens
  d. TEFs and BBFs for Chlorinated Dibenzc-
   p-dioxins (CDDs) w* Chlorinated
   DuMnaofarans(CDFs)
  e. Wildlife
3. Requaat for Comment on Approach
   Considered far Implementing the States'
4. Request to Comment on Alternative
    Approach
B. Reasonable Potential for Exceeding
Numeric Water Quality Standards
1. Existing National Rules and Guidaa
    Standard
             Above the Water Quality
                    •1 iv Excursion
    Above the Water Quality Standard
  c No Reasonable Potential for Excursions
    Above tot Water Quality Standards
  d. Inadequate Information
2. Proposed Procedun 5
  a. Developing Preliminary Effluent
    Limitations
  b.Determmij
tg Whether Then is
i Potential to Exceed the
    Pralimittary EfQuent Limitations
  L Detennining Reasonable Potential Where
    Ten or Mora *™f"nrt Data Points are
    Available and the Effiuant Flow Rate is
    Less than the 7-day. 10-year Flow Rate
    or the Diacbarge is to Open Watam of the
    Great Lakes
                                           e. Consideration of Intake Water Pollutants
                                             When Determining Reasonable Potential
                                           i. Introduction
                                           ii. Current National Approach
                                           (A) Net/Gross Credits for Tedmoiogy-basec
                                             Limits
                                           (B) Consideration of Intake Water
                                             Pollutants for Water Quality-based
                                             Limits
                                           (1) TMDLs
                                           (2) Variances From Water Quality
                                             Standards
                                           (3) Modifications to Designated Uses
                                           (4) Site-specific M"dificatifff« to Criteria
                                           (S) Additional Examples of Application of
                                           iii. Proposed Guidance
                                           iv. Alternative Options Considered
                                           (A) Option 1
                                           (B) Option 2
                                           (Q Option 3
                                           fD) Option 4
                                           v. Request for Public Comment
                                           L Other Applicable O
                                         F. Whole BIHutnt Toxidty
                                         1. Background
                                         2. Current National Guidance
                                           b. Bxiating Technical Guidance
                                         3. Great Lakes Guidance
                              L Acute Taaddty Control
                              iL Chronic Taxidty Control
                              ULIfameric end Narrative Crlt
                              b. WET Test Methods
                              c Permit Conditicas
                              L Data Indicates the Reeeonabk
                                for WET
                              » h»«Ml>lf4a«« pm fo Prtff »»'"• the
                                Reasonable Potential for WET
                              UL Datafaidicatea No Reasonable Potential
                                for WET
                              d. K<*%wnaM+ PiHi*ntial Peiei miff********
                              L Characterizing Acute and Chronic
                                Toxidty Values
                              iL Specific Conditions far Acute Toxidty
                              iii. Specific Conditions far Chronic
                                Taxidty
                              e. State and Tribal Adoption of Guidance
                                          1. Expression of WQBELS as Cottoantratioc
                                             and Mats Loading Rates
                                          2. Piumlurai to Calculate Matt Loading
                                             Limits
                                          3. Special Provisions Applicable to Wet-
                                             weather Discharges
                                          R WQBELS Below the Level of
    Where Ten or More EtBuent Data Points
    are Available and the Efiluent Flow Rate
    is Bqual to or Greater Than the 7-day. 10-
    year Flow Rate
   lif  jt~~ mtiihij ffeeannahln Ptrtmtial
    Where Then is at Least One but Less
    Than Ten Data Points Available
   c Determining the Need far Water Quality-
    based **B"""> tr**!!*^******* in the
    Absence of Effluent Monitoring Data for
    ASpedfic Facility
                                                                     3. Determinations of Cosu
                                                                     4. Estimated Facility Compliance Costs
                                                                       a. Basic Considerations
                                                                       b. POTW Cosu
                                                                       c. Monitonng Costs
                                                                     5. Extrapolation of Total Compliance-Costs
                                                                         for Sample to the Great Lakes
                                                                         Community of Point Sources
                                                                     C Limitations of the Analysis
                                                                     1. Limitations in Scope
                                                                     2. impact of Tecnnical Assumptions
                                                                     D. Findings
                                                                     l. General Observations
                                                                     2. Specific Findings
                                                                     E. Provisions in the Proposed Guidance
                                                                     Available for Use at States' Discretion to
                                                                     Mitigate Cfftnp*'if*t* Costs
                                                                     1. Additional Time to Collect Data to Derive
                                                                         a Numeric Tier I Criteria or a New Tier
                                                                         D Value
                                                                     2. Variances From Water Quality Standards
                                                                     3. Mixing Zones
                                                                     4. Reasonable Potential to Exceed Water
                                                                         Quality
                                                                     5. Designated Use Modification
                                                                     6. Site-specific Criteria
                                                                     7. Total Maxmram Daily Load (TMDLVWaste
                                                                         Load Allocation (WLA)
                                                                     a. Cfflp'rtnrt fcheriiiiai
     for Pollutants for Which Gnat Lake* Tier
     D Vatoea an Not Available
                             2. Gnat Lake* Guidance
                             3. State and Tribal Adoption Requir
                             4. Options Considered
                             I f"f*rfjiltml*r» Schfthllff

                             DC. Executive Order 22291
                             A. Introduction and Rationale for 1
                             Costs and Benefits for the Gnat Lakes Water
                             Quality Guidance

                             B. Overview of Protected Costs Attributable
                             to the Gnat Lakes Water Quality Guidance

                             2! Methodology for Estimating Costs to Point
                                 Sources Attributable to the Great Lakes
                                 Water Quality Guidance
F. Sensitivity Analysis
l.TterlBCCa an Pound Bineccumulating

  a. Step 1-foUatioB Pnvention
  b. Step 2~Ah«nativecr Enhanced
    XfMtfflflBt
  cStepj-Sodal/Economichnpact
  d. Summary
3. Futun '"MtilHiit of BCCs
4. Blimination of Mixing Zones far BCCs
5. Prevalence of Tier 0 BCCs and Potential
    BCCs
6. Evaluation of Intake Pollutant Options
7. Summary
G. Futun Analyses

H. Cost-effectiveness
1. mtroduction
2. Pollutant '•"t'*iiig« Reductions
3. Toxidty-Weighted '•"•^"g' Reduction
4. Cost-effectiveness
5. Sensitivity Analysis
L Overview of Projected Benefits Attributable
to the Gnat Lakes Water Quality Guidance

 2. Qualitative Assessment of Benefits
    Associated With the Great Lakes Water
    Quality Guidance
  a. Sensitivity and Unique Attributes of
                                                                                      b.Natun of Toxic PoUB
                                                                                                                      •dbv
                                                                                        the GLWQG ""* ****p*"^Tfon* for Risk
                                                                                        Reduction
                                                                                      c. Overview of Exposed and Sensitive
                                                                                        Popuktions
                                                                                    3. Eormnmic Concepts Applicable to the
                                                                                        Quantitative Benefits Analysis
                                                                                      a. The Economic Concept of Benefits
                                                                                      b. Benefit Categories Applicable to the
                                                                                        GLWQG
                                                                                    4. Limitation of the Benefits Analysis
                                                                                      a. Causality: Linking the GLWQG to
                                                                                        Beneficial Outcomes

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2QS06          Ttdeal togiMer  /  Vol. 58. No. 72  /  ftiday. April  16. 1993 / Proposed Rules
  b. Temporal. Spatial and Tr	
  i. The Tune Path to Ecosystem Recovery
    From Near-term H**tli«M'« in Toxic
  ii- The Geographic Scop* of Conumiiution
    •ad of Be
genaranng ActivitiM
    	      „   tungAc
    Throughout the Great lakes Watershed
    Ecosystem
  iii. Existing Data Sources
  c. Baseiine and Benefits Attribution Issues
  d. Contingent Valuation Method lames
  i. Using CVM to Estimate Use -
    (Recreational) Benefits
  ii. Using CVM to Measure Nonuse Values
5* Cost^uacti veness of the Proposed
    Guidance at Three Sites
6. Future Anaiysu

X. Regulatory Flexibility Act

XL Papmmrk Rfducaon Act

XV. JudJdoJ Jtewew of Provisions Not
XUL Supporting Documents
AppaadixtDtbaPn
Watar Quality Initiative Technical Support
Document far Wildlife Criteria
                                                     A-5

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           APPENDIX B:



           APPENDIX A



       UNCERTAINTY FACTORS







               to








              DRAFT



   Technical Support Document



        Methodologies for



Hunan Health Criteria and Values



     Great Lakes Initiative







          January 1993

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A.   INTRODUCTION
     Uncertainty factors (also called safety factors)  are intended
     for  use in extrapolating toxic  responses  thought to have a
     threshold  (i.e.,  noncarcinogenic  effects).     "Uncertainty
     factor"  is defined as a number  that  reflects the degree or
     amount   of  uncertainty  that  must   be   considered  when
     experimental  data in .animals  are  extrapolated to man  (EPA,
     1980).    In  addition,  uncertainty  factors  are  used when
     extrapolating from small populations of humans to  the  entire
     heterogeneous human population and when extrapolating  from a
     single  animal  species to wildlife communities.   The use of
     uncertainty factors in extrapolating animal toxicity data to
     acceptable exposure levels for  humans has been the cornerstone
     of regulatory toxicology (National Academy of Sciences,  1980).
     This  appendix will provide the risk assessor with  additional
     guidelines, rationale and information concerning the selection
     of uncertainty factors.

     Because  of the  high  degree  of judgment  involved  in the
     selection  of  uncertainty   factors,   the  risk   assessment
     justification  should include  a  detailed discussion  of the
     selection  of the  uncertainty factors  along with the data to
     which they are applied.

     This  report  is organized  with  the  recommended uncertainty
     factors listed in Part B for quick reference,  and a  discussion
     of those factors and their support in Part C.  Also included
     in Part C is  a  discussion  of the exposure  duration terms
     "subacute", "subchronic", and  "chronic".


B.   RECOMMENDED UNCERTAINTY FACTORS

     1.   A 10-fold factor is recommended when extrapolating from
          valid  experimental  results   from  human  studies  of
          prolonged exposure.

     2.   A 100-fold factor is recommended when extrapolating from
          valid  results  of  long-term  studies  on  experimental
          animals with  results of  studies of human exposure not
          available or scanty (e.g., acute exposure only).

     3.   A factor of  up to 1000 is  recommended when extrapolating
           from animal  studies  for which the exposure duration is
          less than chronic (i.e.,  less than 50% of the lifespan)
         -or-when other significant deficiencies in study quality
          are present,  with no useful  long-term or  acute human
          data.

     4.   An additional uncertainty factor or between l and 10 is
          recommended depending on the severity and sensitivity of


                               B-l

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          the adverse effect when extrapolating from a LOAEL rather
          than a NOAEL.

     5.   An  additional  uncertainty factor  of up  to 10 may be
          applied when there are limited or incomplete subacute or
          chronic toxicity data, such as with short-term repeated
          dose animal studies where the exposure regime involves a
          limited period that  is markedly short-term relative to
          the lifespan of  the test species  (e.g.,  28-day rodent
          NOAEL).


C.   DISCUSSION
     Dourson  and  Stara  (1983)  reviewed  available  literature on
     uncertainty  factors  which are used to  estimate  acceptable
     daily intakes (ADIs) for toxicants.   They found that the use
     and  choice  of  these  factors  is   supported  by  reasonable
     qualitative biological premises and  specific biological data.
     Therefore,  in the absence of adequate chemical-specific data,
     uncertainty factors for criteria derivation may be selected
     according to reasonable assumptions  and approximations rather
     than total  arbitrariness.  They presented a set of guidelines
     for the use of uncertainty factors based  on those utilized by
     the  FDA,  WHO,  NAS,  and  EPA, indicating  consistency  and
     widespread acceptance among the scientific community.  Those
     guidelines  have  been adapted herein for use in risk assessment
     under  the  Great  Lakes  Initiative.   Their  rationale  and
     experimental  support  are  discussed below.   The  guidelines
     should   not   be  misconstrued  as  being  unalterable  and
     inflexible.  They are  intended to help ensure appropriateness
     and consistency of risk assessments. They should be regarded
     as general  recommendations, with the realization that the data
     for  a  particular  chemical may  be such that a  different
     uncertainty factor would be more appropriate.

     1.   A 10-fold factor is recommended when extrapolating from
     valid experimental  results from human studies  of  prolonged
     exposure.  People of  all  ages, states of health,and genetic
     predispositions may  be exposed to environmental contaminants.
     The 10-fold factor is intended to offer  protection for the
     sensitive subpopulations (the  very young, the aged, medically
     indigent, genetically predisposed,  etc.), since the observed
     no-  effect  level  is  generally based   on  average  healthy
     individuals.    Experimental support for this 10-fold factor
     is provided by log- probit analysis  and the study of composite
     human sensitivity (Dourson and Stara, 1983).

     However,  Calabrese  (1985)  has  presented  data  on  human
     variability  in  several  physiological   parameters  and  in
     susceptibility to several diseases,  and concluded that human
     variation may range up to two or three  orders  of magnitude.
     While human variation in the metabolism of various xenobiotics

                               B-2

-------
may  have a 1000-fold range, Calabrese (1985) noted that  the
vast majority  of the responses addressed  fell clearly within
a  factor of 10.   Another study on key human pharmacokinetic
parameters indicates that  the  10-fold factor  to encompass
human  variability  may  only  capture the variability  among
normal healthy adult humans.  That report recommends  further
study  to determine  the degree  of additional susceptibility
among sensitive subpopulations  (EPA,  1986).

Given the heterogeneous and highly outbred state of the  human
population,   and   the  multifactorial  nature   of   disease
susceptibility, reliance on the adequacy of the 10-fold factor
for   extrapolation   to   "safe"  levels   appears  somewhat
precarious.   But  because of  its  history  of use and  current
widespread acceptance,  this factor may continue to be used
until the  availability of new data indicating quantitatively
a more acceptable factor.

2.   A 100-fold factor is recommended  when extrapolating from
valid results  of long-term  studies on experimental animals
with results of studies of  human  exposure not available or
scanty  (e.g..  acute exposure  only).  This  represents the  10-
fold factor for intraspecies  extrapolation (see C.I)  and an
additional  10-fold  uncertainty factor for extrapolating data
from the average animal to  the average man.

The  100-fold uncertainty factor  has  been justified for  use
with the  risk  extrapolation  for  food   additives.    That
justification  has  been based on differences in body  size,
differences  in food requirements  varying  with  age,  sex,
muscular expenditure, and  environmental  conditions within a
species, differences in water balance of exchange between  the
body and its environment among species, and differences  among
species  in susceptibility  to the toxic  effect of a  given
contaminant  (Bigwood,  1973).    The use of  the  100-fold
uncertainty  factor  has  also been  substantiated  by  citing
differences  in susceptibility between animals and humans to
toxicants,   variations   in   sensitivities  in   the    human
population,  the  fact that  the  number of  animals  tested is
small compared with the size of  the human  population that may
be exposed, the difficulty in estimating human intake,  and the
possibility of synergistic action among chemicals  (Vettorazzi,
1976).

On a dose per unit  of body weight  basis, large animals (e.g.,
man)  .are-generally more sensitive to  toxic effects than  small
animals  (e.g., rats, mice).  This principle is attributed to
the  relationship between animal  size and pharmacokinetics,
whereby  the tissues of a  large  animal   are  exposed  to a
substance (mg/kg dose) for a much longer time  than the tissues
of a small  animal.   This  principle has  been  demonstrated
experimentally. The pharmacokinetic processes underlying this

                          B-3

-------
phenomenon  include:    in general, large  animals metabolize
compounds more  slowly than do  small  animals;  large animals
have many more susceptible cells; in large  animals, substances
are distributed more  slowly and tend to persist longer; the
blood volume  circulates  much more rapidly in small animals.
Thus, for the same mg/kg dose, human  tissues are  exposed to a
substance for a much longer time than rodent tissues  (National
Academy of Sciences, 1977).

Experimental  support  for the additional 10-fold uncertainty
factor  when  extrapolating  from  animal  data  to humans  is
provided by studies on body-surface area dose equivalence and
toxicity  comparisons  between humans  and different  animal
species  (Dourson  and Stara,  1983).   On a dose  per unit of
body-surface area basis,  the effects seen in man are generally
in the same range as those seen in experimental animals.  An
interspecies adjustment factor accounts for differences in mg
per kg body weight doses due to different body-surface areas
between  experimental  animals  and man.   The factor may be
calculated by dividing the average weight of a human (70 kg)
by the weight of the test species (in kg)  and taking the cube
root of  this value.   Thus on  a body weight basis, man is
assumed to be more sensitive than the experimental animals by
factors  of  approximately  5  and 13   for rats  and  mice,
respectively. For most experimental animal species (i.e., all
species  larger  than  mice),  the  10-fold  decrease  in  dose
therefore appears to incorporate  a  margin of safety.   For
mice, the  interspecies adjustment factor  suggests  that the
additional  10-fold   uncertainty  factor   for  interspecies
extrapolation to  humans  is not  large enough  (Dourson  and
Stara, 1983). Nevertheless, the additional 10-fold factor is
considered  adequate  to  adjust from  mice to  humans  when
chemical-specific data are not available.

3.   A factor of UP to 1000 is recommended when extrapolating
 from animal studies for which the exposure duration is less
than chronic  i.e..  less than 50% of the  lifesoan)  or when
other significant deficiencies  in study duality are present.
with no useful long-term  or acute human data.  This represents
the 10-   fold  factors  for  intraspecies and  interspecies
extrapolation (see  c. 2), and an additional uncertainty factor
of up to 10-fold for extrapolating from less than chronic to
chronic animal exposures (or when the data are significantly
flawed in some other way).  Injury from chronic exposure may
occur in at least three ways:  by accumulation of the chemical
to a.critical concentration at  sites of action sufficient to
induce  detectable  injury;by accumulation  of injury  until
physiological reserves can no onger compensate (i.e., repair
is never complete); or after  a  long, latent period beginning
with an  exposure  that has an unrecognized biological effect
and precipitates the eventual appearance  of injury  (National
Academy of Sciences, 1977).  Obviously,  sufficient duration of

                          B-4

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 exposure is necessary in order for the effects seen in chronic
 toxicity to become manifest.  Subchronic toxicology  studies
 may not offer reliable means for assessment of long-term toxic
 effects in  animals,  let along extrapolation  to  chronic
 effects in man (National Academy of Sciences, 1977) . However,
 it  is often the case  that  a good quality,  chronic exposure
 study for a particular chemical is unavailable.  The intention
 of this additional uncertainty factor is to enable the use of
 subchronic  or flawed studies to protect against the  risk of
 adverse effects which  might only appear with chronic  dosing.

 Experimental  support for the additional uncertainty factor is
 given by literature reviews which compare subchronic NOAELs
 and chronic NOAELs for many compounds (McNamara, 1971; Weil
 and  McCollister,  1963).    The  studies  reviewed by  those
 investigators employed a variety of  rodent and non-rodent
 species.  The duration of the subchronic exposures was  usually
 90 days, but  ranged  from 30 to 210 days.  Wide  variations in
 endpoints and criteria for adverse effects were encountered in
 these literature reviews.   However, their findings do give a
 rough indication of the general subchronic and chronic NOAELs
 for other than carcinogenic  or reproductive effects. For over
 50% of the  compounds tested,  the chronic NOAEL  was less than
 the 90-day  NOAEL by a factor  of 2 or  less.   There was some
 indication  that chronic  dosing may result in the development
 of tolerance  toward certain chemicals, as the  chronic NOAEL
 was larger than the 90-day NOAEL in a few cases. However,  it
 was also found that the chronic NOAEL may be less than  the  90-
 day NOAEL by a factor of 10 or more.   The  latter situation
 appeared to be uncommon.  Therefore, these reviews report that
 the  additional  10-fold uncertainty  factor  appears  to   be
 adequate or incorporate a margin of safety in the majority of
 cases.

 As the  literature reviews  by McNamara  (1971)  and Weil  and
 McCollister   (1963)  are limited  and  the studies  reviewed
 utilized a variety of toxicologic endpoints with questionable
 sensitivities,  one must be cautious   in  interpreting their
 conclusions.  But for lack of data to the contrary, it  appears
 that application of the additional  10-fold uncertainty factor
 is appropriate and justified when extrapolating a NOAEL from
 a 90-day study to a chronic NOAEL estimate. This practice may
 underestimate  the  true  chronic  NOAEL  far more  often than
 overestimating it, thus adding a margin of safety to the risk
 calculations.

 One remaining question regarding exposure duration  is:   At
what point is the duration considered adequate,  such that the
 additional uncertainty factor of up to  10 is  unnecessary?   In
 other words,  how is "chronic" defined for the  sake  of this
guideline?
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At  this point,  further discussion  of the  terms "chronic"
"subchronic",  and  "subacute",  is  necessary.    The  term
"subacute"  has been used  to describe a  duration less than
subchronic, while it has also been used as a term analogous to
subchronic.   EPA (1980) describes  "subacute"  exposures (in
this case, analogously to "subchronic") as often exceeding 10%
of  the  lifespan,  e.g.,  90 days for  the  rat  with an average
lifespan  of  30  months.   However,  as pointed out by the
Organization  for Economic Cooperation and Development  (OECD,
1981),  the  term "subacute"  is semantically  incorrect.   The
OECD  prefers to  use  the  phrase  "short-term  repeated dose
studies",  referring  to  14,  21   and 28  day studies,  to
distinguish from "subchronic" studies of greater duration.

"Subchronic"  is generally defined as part of the lifespan of
the  test  species, although  opinions differ on the precise
definition.   Klaassen  (1986) defines "subacute" as repeated
exposure to a chemical for one month or less, and "subchronic"
as  repeated exposure for  1-3 months.   Chan  et  al.   (1982)
describe "subchronic" exposure durations as generally ranging
from 1  to 3 months in rodents and  one year  in longer-lived
animals (dogs, monkeys), or  for part (not exceeding 10%)  of
the  lifespan.  Stevens  and  Gallo  (1982)  define "long-term
toxicity tests" (encompassing subchronic and chronic toxicity
studies) as studies of  longer than 3 months  duration,  i.e.,
greater than  10% of the  lifespan in the laboratory rat.  EPA
(1985)  describes  "subchronic"  toxicity testing as involving
continuous or repeated  exposure for a period of 90 days,  or
approximately 10% of the lifespan for rats.

The various definitions  offered for "chronic"  are generally
inconsistent.  Klaassen  (1986) defines "chronic" as repeated
exposure for  more than  3 months.   According  to the National
Academy of  Sciences (1977),  chronic  exposure  in  animals  is
generally considered to  be at least half  the life span.  In
estimating chronic  SNARLs, the National  Academy of Sciences
(1980)  in most cases utilized data from studies  lasting  a
"major  portion of the  lifetime of the experimental animal".
According to the EPA's Health Effects Testing Guidelines  (EPA,
1985),  chronic toxicity tests should  involve  dosing  over  a
period  of at least 12  months.    The application  of  their
guidelines,  they  add,   should generate  data  on which  to
identify the  majority of chronic  effects  and shall serve to
define long-term dose-response relationships.  The OECD  (1981)
states that the division  between subchronic and  chronic dosing
regimes is-sometimes taken as 10% of the test animal's life
span.   They  also  state that  the duration of the exposure
period  for  chronic toxicity studies should  be at  least  12
months.   They describe  "chronic" as prolonged and repeated
exposure  capable  of  identifying  the majority  of  chronic
effects and to determine dose-response relationships.
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Others  have  investigated the  delayed appearance  of toxic
effects  which night be missed under shorter dosing regimes.
Frederick   (1986)  conducted  a  pilot  survey  of  new drug
evaluators  for incidences of delayed  (greater than  12  month)
drug-induced  pathology.   It was  concluded that  new toxic
effects  "not  infrequently" arise after one year of  dosing in
rodents.  It was  further stated that those findings formed the
basis for the conclusion  of the Bureau of Human Prescription
Drugs:  the duration of the long-term toxicity tests of drugs
that are likely  to be used in man  for more than a few days
should be at  least 18 months.   Glocklin (1986)  reviewed the
issues  regarding  testing requirements  for new  drugs,  and
concluded that 12 month chronic toxicity studies seemed to be
an appropriate requirement for characterization of  the dose-
response .

It is evident that there are discrepancies in the qualitative
and  quantitative   characterization  of  "chronic"  animals
studies.  An appropriate and reasonable working definition for
"chronic" would  appear to  be at  least half the  life span
(therefore, at least  52 weeks for rats and at least 45 weeks
for mice).  Qualitatively, "chronic" means that the exposure
duration was sufficient to represent a full lifetime exposure,
in terms of  dose-response  relationships.  For example, a study
providing an experimental NOAEL which approximates a lifetime
NOAEL is considered a chronic  study.   It is recognized that
the above  quantitative definition  (at least half  the life
span)  does  not demonstrate the flexibility  inherent  in the
above qualitative description.   That flexibility reflects the
vast  differences  in  the toxicology  of various  chemicals:
demonstration  of  a  lifetime NOAEL  for some chemicals  may
require dosing for half the life span, while  the toxicology of
most chemicals may allow demonstration  of  a lifetime NOAEL
under a much shorter dosing regime.  It may be argued that the
lifetime NOAEL for noncarcinogenic effects of many chemicals
can be demonstrated in rodent  studies of much less than one
year.  While the previously-discussed works of McNamara  (1971)
and Weil and McCollister  (1963) support that view, they also
demonstrate that the chronic NOAEL may be less than the 90-day
NOAEL by a factor  of  10 or more, for some chemicals.

This discussion  is necessary in order to properly interpret
the uncertainty  factor guideline,  which recommends that the
additional uncertainty factor of up to 10 be  applied when the
exposure duration  is  less than "chronic".  The intent of the
uncertainty factor is to  adjust  the experimental  NOAEL to a
lifetime NOAEL in  those cases where  the lifetime NOAEL was
presumably not adequately demonstrated.  The key issues are
summarized in  the  following points and recommendations:

a.  An  acceptable quantitative  definition  of  "chronic"  is
elusive.   Due to  differing  toxicological  properties,  the

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necessary minimum exposure duration to demonstrate a lifetime
NOAEL  differs  widely  among  chemicals.    A  qualitative,
philosophical definition of chronic is:  "Chronic" is when the
exposure duration is sufficient for the identification of the
majority  of   long-term  effects  and  their  dose-response
relationships.  Therefore,  a "chronic" study reporting a NOAEL
is  one which  can  be  reasonably  presumed  to predict  the
lifetime NOAEL.

b.   The use  of scientific judgment  is predominant  in  the
decision of when chronic exposure conditions exist, and hence,
when   the   additional  uncertainty   factor   is   no  longer
appropriate.

c.  That scientific judgment should be guided by a review of
all    available   pertinent    data,     e.g.,    metabolism,
pharmacokinetics, bioaccumulation,  mechanism of action, target
organ characteristics, potential for latent effects, etc.

d.  Available reviews of rodent studies indicate that, for
many chemicals, studies of much less  than one year duration
can provide reasonable estimates of lifetime NOAELs.  However,
it is also recognized that the toxicological characteristics
of   some   chemicals  will  prevent  the   qualitative   and
quantitative demonstration of latent adverse  effects and a
lifetime NOAEL if the duration is less than one year.  If the
lack of additional data  prevents scientific judgment in these
cases, 50%  of the  lifespan (52 weeks  for rats; 45 weeks for
mice) may be considered the minimum necessary duration for a
"chronic" exposure. Application of the additional uncertainty
factor for  these apparently "subchronic"  studies  may later
provide to be excessively conservative in some cases.  But, if
the  toxicologic  database  is  inadequate,  the  additional
uncertainty factor should be included,  both  as  a  matter of
prudent  public policy  and  as  an incentive  to others  to
generate the appropriate data.

e.  Ordinarily, the additional 10-fold factor may be applied
for all rodent  studies  of 90  days  duration, unless there is
chemical-specific  data  indicating  that  would be unnecessary
and overly conservative.

f.  For rodent studies  of between  90 days and 12 months
duration, the use of the additional  10-fold uncertainty factor
is best  determined by  professional judgment.   As described
above, ..if -data are  not  available  to  sufficiently  guide
professional judgment,  then such  studies  may be  subject to
part or  all of the  additional 10-fold factor.   A "sliding
scale" or between 1 and  10 is  a reasonable means of selecting
a  lesser  factor  when  10  appears excessive.   Under  this
concept, the additional  uncertainty factor applied may vary on
a scale  of one to  ten  according to  how  closely  the dosing

                          B-8

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     duration  approached  50%  of  the  lifespan.    Of  course,
     consideration must be given of the study quality and the other
     pertinent data mentioned in 3.c above.  A 90-day rodent study
     would be  subject to  a  10-fold additional  factor,  if study
     quality is otherwise nominal and other chemical-specific data
     are lacking.  A nominal-quality study, with  exposure over 50%
     of  the  lifespan,   would be  subject  to  a  "1",  i.e.,  no
     additional adjustment. Situations where the exposure duration
     is  between  90 days  and 50% of the lifespan,  and/or study
     quality is  flawed,  must  be  handled on a case-by-case basis.
     This  "sliding  scale" concept  may  offer  guidance  to  the
     scientific  judgment that will be necessary.

     Dosing duration is but one parameter upon which to assess the
     adequacy of a study.  Other deficiencies in the study design
     may cause increased concern about the validity of the reported
     NOAEL or LOAEL.  Therefore, risk assessors may utilize part or
     all  of  this   additional  10-fold  uncertainty  factor  to
     compensate for data which appears less-than-adequate.  Factors
     which may affect the degree  of  confidence in the data include
     the number  of animals per  dose group, the sensitivity and
     appropriateness of the endpoints, the quality of the control
     group, the  exposure  route,  the dosing schedule,  the age and
     sex of  the  exposed animals, and the  appropriateness  of the
     surrogate species tested, among others.  EPA's Health Effects
     Testing Guidelines (EPA, 1985) provide specific information on
     the desirable  qualities of subchronic and  chronic  toxicity
     tests.

4.   An  additional  uncertainty  factor of  between 1  and 10  is
     recommended depending on the severity and sensitivity of the
     adverse effect when extrapolating from a LOAEL rather than a
     NOAEL.  This  uncertainty factor reduces the  LOAEL  into the
     range of  a NOAEL,  according to  comparisons of LOAELs  and
     NOAELs for  specific  chemicals.   There is evidence available
     which indicates,  for a  select set  of chemicals, 96%  have
     LOAEL/NOAEL ratios of 5 or less, and that all are 10 or less
     (Dourson and Stara,  1983).   In practice the  value  for this
     variable uncertainty  factor has been  chosen by the  U.S.  EPA
     from values among  1  through 10 based  on the  severity  and
     sensitivity of the adverse effect  of the LOAEL.  For example,
     if the LOAEL represents liver cell necrosis,  a higher value is
     suggested for this  uncertainty  factor  (perhaps 10).   If the
     LOAEL is fatty  infiltration of the liver  (less  severe than
     liver cell necrosis),  then a lower value is suggested (perhaps
     3;  see  .the  following discussion).   The  hypothesized NOAEL
     should be closer to  the  LOAEL showing less  severe  effects
     (Dourson and Stara, 1983).

     In  some  cases  the  data  do   not  completely  fulfill  the
     conditions  for  one  category of  the  above  guidelines,  and
     appear to be intermediate between  two categories.   Although

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     one  order  of magnitude  is generally  the smallest  unit of
     accuracy  that  is  reasonable  for  uncertainty factors,  an
     intermediate value may be used if  felt  necessary (Dourson,
     1987).    According  to  EPA  (1980),  such  an  intermediate
     uncertainty factor may be developed based on  a logarithmic
     scale  rather  than  a  linear  scale.   Calculating the  mean
     logarithmically may be the more appropriate  option,  because
     the precision of all uncertainty factor estimates is poor, and
     a logarithmic scale is the best way to estimate the mean of
     two imprecise estimates  (Dourson, 1987).   Halfway between 1
     and 10 is approximately 3.16 on a logarithmic scale.  However,
     so as not to  imply excessive  accuracy in the estimate,  that
     mean value should be rounded-off to 3 (Dourson, 1987).

5.   An additional uncertainty  factor of UP to 10 may be applied
     when  there  are limited  or incomplete  subacute  or  chronic
     toxicity data,  such as with short term repeated dose animal
     studies where the exposure regime involves a limited period
     that is markedly short-term relative to  the  lifespan of the
     test species  (e.g.. 28-davrodentNOAEL).  As previously noted
     (see C.3) the OECD (1981) distinguishes between 14, 21 or 28
     day studies and "subchronic" studies of greater duration, by
     referring to the former as "short-term repeated dose studies".
     The short-term  studies are commonly conducted  by  the NTP to
     enable appropriate dose selection in subchronic studies (NCI,
     1976).   When a limited  database exists,  short-term animal
     studies of 28 days or longer may be of sufficient quality to
     support  risk  assessment  of  potential  chronic  exposure.
     Because the duration of  exposure  is substantially less  than
     the 90-day period discussed under C.3, the risk assessment may
     require an additional uncertainty factor in conjunction with
     the 1000-fold factor recommended under C.3.  As guidance, an
     additional  factor   of  up   to  10  is   recommended  when
     extrapolating from  a  short-term  NOAEL  (e.g.,  28 days)  to
     subchronic duration (e.g., 90 days).

     Although the  extrapolation from oral LD5Qs to  chronic  oral
     NOAELs has been  reported  by several  investigators  (Venman and
     Flaga, 1985; Layton et al., 1987; McNamara, 1971), there has
     been relatively  little  investigation of the extrapolation from
     short-term  NOAELs  (much  less  than   90 days  in rodents)  to
     chronic NOAELs.  EPA (1989) states that when experimental data
     are available only for  shorter durations than desired for
     subchronic RfD derivation an additional uncertainty factor is
     applied.  However,  further details on the selection of an
     adequate and appropriate uncertainty factor for those "shorter
     durations" are not provided.  Weil et al.  (1969) evaluated the
     relationship between 7-day, 90-day and 2-year minimum effect
     levels (MiE) for 20 materials via feed exposure.  They found
     that  the median  value  for a  90-day MiE was obtained by
     dividing the 7-day MiE by a factor of 3.  The 95th percentile
     for the 90-day MiE was obtained by dividing the 7-day MiE by

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6.2.  Also noteworthy is the finding that the 95th percentile
for the 2-year MiE was obtained by dividing the 7-day MiE by
a factor of 35.3.

These data, albeit limited, support the general principle that
as exposure duration decreases,  the ability of the data to
demonstrate   chronic,  dose-response   relationships   also
decreases.  While an additional 10-fold uncertainty factor may
reasonably  and appropriately  convert a 90-day  NOAEL to a
surrogate chronic NOAEL,  an additional uncertainty factor may
be necessary  when extrapolating from short-term  exposures.
Applying an additional  uncertainty factor of up to 10 will
help ensure that the risk assessment  for  potential chronic
exposures is adequately conservative,  i.e., the true chronic
NOAEL will generally not be overestimated.
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Bigwood, E.  1973.   The Acceptable Daily Intake of Food Additivies.
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     Support   of  Uncertainty   (Safety)   Factors.     Regulatory
     Toxicology  and Pharmacology.  3:224-238.

Calabrese, E.  1985.  Uncertainty Factors  and  Interindividual
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Chan, P., O'Hara,  6. and A. Hayes.  1982.  Principles and Methods
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Dourson,  M.    1987.    U.S.  EPA.    Environmental   Criteria  and
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Dourson,  M.  and  J.   Stara.    1983.    Regulatory  History  and
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Frederick,  G.    1986.   The  Evidence  Supporting  18 Month Animal
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Glocklin, V.   1986.  Justification for  12 Month Animal Studies.
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