Draft Report C737-01
GUIDANCE MANUAL FOR ASSESSING HUMAN HEALTH RISKS
FROM CHEMICALLY CONTAMINATED
FISH AND SHELLFISH
Submitted to:

Battelle New England Marine Research Laboratory
Duxbury, Massachusetts
For:

U.S. Environmental Protection Agency
Office of Marine ind Estuarine Protection
Washington, DC
December 1987
By:

PTI Environmental Services, Inc.
13231 SE 36th Street, Suite 200
Bellevue, Washington 98006

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                                CONTENTS


                                                                       Page

LIST OF FIGURES

LIST OF TABLES

ACKNOWLEDGMENTS

INTRODUCTION                                                           1

     OBJECTIVES                                                           1

     ORGANIZATION                                                       2

     BACKGROUND                                                        2

         Applicability of this Guidance Manual                                   4
         Relationship of this Manual to Other EPA Documents                       4
         Relationship of Fisheries Risk Assessment to Water Quality
           Criteria and Standards                                              5
         Relationship of EPA Risk Assessment Methods to FDA Risk
           Assessment Methods                                                6

OVERVIEW OF RISK ASSESSMENT AND RISK MANAGEMENT                    8

     MAJOR STEPS IN RISK ASSESSMENT                                      8

     NEED FOR RISK ASSESSMENT APPROACH                                 8

     USES OF RISK ASSESSMENT                                            10

HAZARD IDENTIFICATION                                                 12

     CONTAMINANTS OF CONCERN                                          12

     TOXICITY PROFILES                                                   13

     SOURCES OF INFORMATION                                            14

DOSE-RESPONSE ASSESSMENT                                               16

     EXPOSURE AND DOSE                                                 16

     DOSE-RESPONSE RELATIONSHIPS                                       16

     CARCINOGENIC POTENCY FACTORS                                    17

     REFERENCE  DOSES                                                    19

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     SOURCES OF INFORMATION                                             ]9

          Carcinogenic Potency Factors                                           19
          Reference Doses                                                     20

EXPOSURE ASSESSMENT                                                     21

     TISSUE CONCENTRATIONS OF CONTAMINANTS                            21

          Study Objectives and General Sampling Design                             24
          Selection of Target Species and Size Classes                                28
          Sampling Station Locations                                             32
          Time of Sampling                                                    34
          Kinds of Samples                                                    35
          Sample Replication                                                   38
          Selection of Analytical Detection Limits and Protocols                       38
          QA/QC Program                                                     39
          Documentation and QA Review of Chemical Data                           40
          Statistical Treatment of Data                                            41

     ANALYSIS OF SOURCES,  TRANSPORT, AND FATE OF CONTAMINANTS       42

     EXPOSED POPULATION ANALYSIS                                        43

          Comprehensive Catch/Consumption Analysis                               45
          Assumed Consumption Rate                                            47

     EXPOSURE DOSE DETERMINATION                                       49

          Single-species Diets                                                   49
          Mixed-species Diets                                                   50

     SOURCES OF INFORMATION                                             51

RISK CHARACTERIZATION                                                   52

     CARCINOGENIC RISK                                                   52

     NONCARCINOGENIC EFFECTS                                            53

     CHEMICAL MIXTURES                                                   55

PRESENTATION AND INTERPRETATION OF RESULTS                            56

     PRESENTATION FORMAT                                                56

          Summary Tables                                                     56
          Summary Graphics                                                   57

     RISK COMPARISONS                                                     57

     SUMMARY OF ASSUMPTIONS                                             58

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    UNCERTAINTY ANALYSIS                                           59

        Sources of Uncertainty                                            59
        Approaches to Uncertainty Analysis                                  6]

    SUPPLEMENTARY INFORMATION                                     62

REFERENCES                                                          64

APPENDIX A - EPA OFFICE OF WATER CONTACTS ON RISK ASSESSMENT FOR FISH
             CONSUMPTION

APPENDIX B - INTEGRATED RISK INFORMATION SYSTEM (IRIS)

APPENDIX C - SOURCES OF INFORMATION FOR TOXICITY PROFILES

APPENDIX D - EVALUATION  OF THE  EFFECTS  OF COMPOSITE  SAMPLING ON
             STATISTICAL POWER OF A SAMPLING DESIGN

APPENDIX E - EVALUATION  OF THE  EFFECTS  OF  SAMPLE REPLICATION ON
             STATISTICAL POWER OF A SAMPLING DESIGN

APPENDIX F - ESTIMATION OF FISH/SHELLFISH CONSUMPTION FROM A NATIONAL
             DATABASE

APPENDIX G - EPA OFFICE OF RESEARCH  AND DEVELOPMENT, ENVIRONMENTAL
             RESEARCH LABORATORIES

APPENDIX H - EPA REGIONAL NETWORK FOR RISK ASSESSMENT AND RISK MAN-
             AGEMENT ISSUES

APPENDIX I -  COMPILATION OF LEGAL LIMITS FOR CHEMICAL CONTAMINANTS IN
             FISH AND FISHERY PRODUCTS

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                                   LIST OF FIGURES
                                                                                Following
Number                                                                            Page

   1     Overview of risk assessment and risk management                             g

   2     Hypothetical example of dose-response curves for a
         carcinogen and a noncarcinogen                                             16

   3     Interaction between environmental factors and exposed
         population factors                                                          27

   4     Summary of recommended marine and estuarine indicator
         species                                                                    31

   5     General sampling station layouts for probability
         sampling in two dimensions                                                 32

   6     Conceptual structure of quantitative health risk
         assessment model                                                           52

   7     Example graphic format for display of quantitative
         risk assessment results for hypothetical study area
         and reference area                                                          57

   8     Plausible-upper-limit estimate of lifetime excess
         cancer risk vs. concentration of a chemical contaminant
         in fish or shellfish  (ppm wet wt.) at selected ingestion
         rates                                                                      57

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                                    LIST OF TABLES
                                                                                 Following
Number                                                                             page

   1      Organic priority pollutants and 301(h) pesticides
          ranked according to octanol-water partition
          coefficients (Kow)                                                           12

   2      Inorganic priority pollutants ranked  according to
          bioconcentration factor                                                      13

   3      Toxicity profile for mercury and PCBs                                       13

   4      Criteria for selecting target species                                           28

   5      Approximate range of cost per sample for analyses of
          EPA priority pollutants in tissues  as a function  of
          detection limits and precision                                                39

   6      Example tabular format for display  of quantitative risk
          assessment for consumption of fish and shellfish                              56

   7      Summary of assumptions and numerical estimates used in
          risk assessment approach                                                    58

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                                ACKNOWLEDGMENTS


     This document was  prepared  by PTI Environmental Services, Inc., under the direction
of Dr.  Robert Pastorok,  for the  U.S. Environmental  Protection Agency (EPA) in partial
fulfillment  of Battelle Contract  No.  L3198(8873)-018D  to PTI Environmental  Services,
and  EPA Contract  No.  68-03-3319  to  Battelle.   Dr. Kim  Devonald  of the Office  of
Marine  and Estuarine  Protection was the Project Monitor  for  EPA.   Dr.  Michael Connor
was the Technical Monitor for Battelle.

     The primary  author of this  report is  Dr. Robert A. Pastorok.   Dr. Kim Devonald
prepared  the  initial  draft of  the  background section  in the  introduction.    The  EPA
Office  of  Pesticide Programs prepared  Appendix  F.   Mr. Pieter  Booth  and Ms.  Carol
Newlin  of PTI Environmental Services and Dr.  Kim Devonald contributed  to the Executive
Summary (under separate binding).    Dr.  Thomas  C. Ginn provided  a  technical  review
and  quality  assurance  for  PTI  Environmental  Services.    Ms.  Carol Newlin  and  Ms.
Sharon  Hinton provided  editorial  and production support.   Portions  of this  report  were
based on a  document  prepared for  the EPA  Region X Puget  Sound Estuary  Program.
That  document,  entitled   Guidance  Manual  for Health  Risk  Assessment of  Chemically
Contaminated  Seafood,  was  prepared while  Dr.  Pastorok  was  an  employee of  Tetra
Tech,  Inc.   Dr.  Leslie  Williams  and Mr. Jonathan  Shields  provided  valuable  technical
assistance in preparing  the guidance manual for EPA  Region  X.  Dr.  John Armstrong of
EPA  Region  X Office  of  Puget  Sound  was  instrumental   in  developing   the  original
concept  of  a guidance  manual  for assessing  human  health risk from contaminated  fish
and shellfish.  Dr. Pastorok also benefited from comments  on the EPA Region  X document
from  participants  at a   workshop   on health  risk  assessment  related  to  consumption  of
fish  and  shellfish.    The workshop,  held in   Westbrook,  Connecticut  on  January 15-16,
1987, was  sponsored by  EPA Region I  and  the  New England  Interstate  Water  Pollution
Control  Commission.

     Valuable comments  on  earlier drafts of this report were  received from  the  following
reviewers:

          Name                                Affiliation

     Donald Barnes             EPA  Office of Toxic Substances

     Bruce R. Barrett           EPA  Water Management Division, Region IV

     Robert Cantilli            EPA  Office of Drinking Water

     Richard L. Caspe          EPA  Water Management Division, Region II

     Michael Connor           Battelle Memorial Institute

     Dave DeVauIt             EPA  Great Lakes National Program Office,  Region  V

     Kim Devonald             EPA  Office of  Marine  and Estuarine  Protection

     Carol Finch               EPA  Great Lakes National Program Office,  Region V

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Kevin G. Garrahan        EPA Exposure Assessment Group

A.R. Malcolm             EPA Physiological Effects Branch

Alvin R. Morris           EPA Water Management Division,  Region III

Edward V. Ohanian        EPA Health Effects Branch, Office of Drinking Water

Kenneth Orloff           EPA Water Management Division,  Region IV

Gerald Pollock            California Department of Health Services

Vacys J, Saulys           EPA Great Lakes National Program Office, Region V

Malcolm Shute            Connecticut Department of Health Services

Paul E.  Stacey            Connecticut Department of Environmental
                         Protection

Brian Toal                Connecticut Department of Health Services

Paul White                EPA Exposure Assessment Group

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                                    INTRODUCTION
      Contamination  of  aquatic  resources by  toxic  chemicals  is a  well  recognized  problem
in  many  parts  of  the  U.S.    High  concentrations  of  potentially toxic  chemicals  have
been  found  in  sediments  and  in  aquatic  organisms from  Puget Sound,  the  Southern
California Bight, northeast  Atlantic  coastal  waters, the  Hudson  River,  the  Great Lakes,
and elsewhere (Malins et al. 1984; Tetra Tech  1985b,d, 1986c; Brown et  al. 1985;  DeVault
et  al. 1986;  Rideout and  Bender 1986).   Heavy  consumption  of  contaminated fisheries
products  by  humans  may  pose  a  substantial  health risk  (e.g., Sonzogni  and Swain 1984;
Swain 1986;  Capuzzo et al.  1987).   This concern  has prompted  recent studies of catch
and  consumption  patterns  for  recreational  fisheries  and  associated  health  risks  (e.g.,
Puffer et al.  1982; Conner 1984; Landolt et al.  1985, 1987; Versar 1985; Swain  1986).

      To  protect the  health of  consumers of fish and  shellfish, information  is needed on
relative  health  risks  associated  with  various  edible aquatic  species, geographic locations,
and consumption rates.    In the past, diverse  models  have  been  used  to  estimate human
health risks from exposure to toxic substances in food [e.g., Cordle et al.  1978;  U.S. Office
of  Technology  Assessment  1979;  U.S.  Environmental  Protection  Agency  (EPA)  1980b;
Food  Safety  Council 1980,  1982; Connor  1984; Tollefson and Cordle  1986).  For consistency
among  EPA  regions  and  programs,   a standardized  procedure  is  recommended  here  for
assessing  human  health  risks  from  consumption  of  chemically  contaminated  fish  and
shellfish.
OBJECTIVES

     The  purpose  of  this  manual  is   to  provide  guidance  for  health  risk  assessment
related  to chemically  contaminated  fisheries  based  on  EPA  approaches  (e.g.,  U.S.  EPA
1980b, 1986a-e, J987a).  The objectives of the guidance manual are to:

     •     Describe the steps of a health risk assessment  procedure for  consumption
           of contaminated fish and shellfish

     •     Provide guidance on presentation of risk assessment results

     •     Summarize assumptions  and  uncertainties  of the recommended  procedure
           for risk assessment

     •     Summarize standard  model  variables  (e.g.,  Carcinogenic Potency Factors
           or  Reference  Doses  for  chemicals)  and criteria  [e.g.,  U.S. Food  and
           Drug  Administration (FDA) action levels]  related  to  risk  assessment,  and
           information sources for updating these values.

The  guidance  provided in  this manual  is  directed primarily at  risk  assessment related  to
recreational  fisheries.    Although  assessment  of  human  health   risks   from  commercial
fisheries  products  is  not  addressed  specifically  in  the examples  provided herein,  many
of the concepts discussed  throughout  the  manual are relevant to risk analysis of commercial
fisheries.

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      This  manual  provides guidance only, and does  not  constitute  a regulatory requirement
of any kind.  The technical  content  is entirely  consistent with approved EPA  procedures
for  risk  assessment,  as published  in the  Federal   Register  (U.S.  EPA  1986a-e).   The
relationship  between  these  procedures and  risk  assessment  approaches used  by  FDA  is
described briefly in the background section below.


ORGANIZATION

      Background   information  on available  health  risk  assessment  guidance  and  use  of
this  manual is provided  in  the  remainder  of   this introduction.   An  overview  of risk
assessment is provided  in  the following  section, including a discussion of  the  distinction
between risk  assessment  and risk  management, and  a  review   of   their  possible  uses.
The   major  steps  of the  risk  assessment  process recommended  herein  are  described  in
subsequent  sections.   Guidance  is  provided  on mathematical models  used  to   estimate
chemical  exposure  and risk.   Sources  of  information  on  toxic  chemicals  and  model
variables  are noted.   Finally,  suggestions  for  presentation  of  risk assessment  results are
provided.   Uncertainties and  assumptions  of the  assessment  approach  described  in  this
manual are summarized.
BACKGROUND

      Risk  analysis encompasses  both  risk assessment and risk management.  Risk assessment
is  a  scientifically based  procedure  to  estimate  the  probability  of adverse  health  effects
from a specific exposure  to  a  toxic agent.   Risk assessment differs from risk management,
although  both  are  elements of  regulatory  decision-making  (National  Research  Council
1983).   Risk  assessment  provides the  scientific basis  for  public policy and action.   In
risk   management, risks  are interpreted in  light  of legislative,  socioeconomic,  technical,
and  political  factors,  and appropriate  controls are  determined.    Risk management often
involves defining  an  acceptable  risk level,  i.e.,  the maximum  risk  considered  tolerable.
Risk management often involves evaluation of  risks in light of potential  benefits associated
with an activity.   For  example, a  risk  manager  might  weigh  the  risks associated  with
chemical  contamination of  fish and  shellfish  against  the health  benefits  (e.g.,  decreased
risk  of heart  disease) associated  with consumption of  fish and shellfish in  place  of red
meat.

      In  September   1986,   EPA  published  final   guidelines  for  assessing  health  risks
related to environmental pollutants.  The guidelines are in  five parts (U.S. EPA 1986a-e):

      •    Carcinogen Risk Assessment

      •    Exposure  Assessment

      •    Mutagenicity Risk Assessment

      •    Health Assessment of Suspect  Developmental Toxicants

      •    Health Risk Assessment of Chemical Mixtures.

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 These guidelines pertain  to health  risk assessment for  all environmental  exposures [e.g.,
 air  exposure;  ingestion  of  water  or  environmentally  contaminated  foods;  and  other
 direct  human  contact  with  contaminated  soils,   water,  sediments,  or  other  materials
 (FR51  No.  185, p.  34049)].   The  guidelines  were  developed through  a  2-year  process
 that  included contributions  and  review by  the larger  scientific  community; full Agency
 consideration of  public comments  in  response to  proposed guidelines on  November  23,
 1984;  and  review and  approval by  the EPA  Science Advisory Board (FR51 No. 185, p
 33992).

      This  guidance  is  in  the  form  of  a  policy statement  and  does  not constitute  a
 regulatory requirement.   The guidance is  intended simply to  describe what EPA believes
 to  be   the   most  scientifically  defensible  methods  for  assessing  environmental   health
 risks,  and  to inform the public  that  these  are  the methods  EPA  will use  in  conducting
 the health risk assessments required in its statutorily mandated programs.

      While  U.S.  EPA's  (1986a-e)  risk  assessment  guidelines  apply  to  all exposure  routes,
 they  do  not contain  detailed information  on application  of  the basic principles  for each
 exposure route.   This guidance  manual provides such step-by-step  assistance for assessing
 health  risks  from   exposure  through  consumption of  chemically  contaminated  aquatic
 organisms.   The  guidance  is applicable to freshwater,  brackish  water, and  saltwater  fish
 and shellfish. It is based entirely on the principles set forth in U.S. EPA (1986a-e).

      As  described  in  a recent  report  by  EPA's Risk  Assessment Council  and  FDA (U.S.
 EPA  and  U.S.  FDA  1987), FDA, EPA,  and  the  states  have  somewhat  differing roles in
 assessing and  managing  risks   from  fish  consumption.    These  roles  are  summarized
 below.

      FDA has  the  lead responsibility for  risk  management of foods in interstate commerce
 or other  products of  national importance  including  fish  and shellfish.  For some  chemicals
 in  foods  (specifically  pesticides),  EPA  assists FDA  in  performing  the   technical  risk
 assessments  that  support risk  management  decisions.   The  federal  government  is  not
 directly   responsible  for  managing  risks  to  individuals  who  consume  unusually large
 amounts of  foods not  in  interstate commerce or foods harvested  from  locally contaminated
 areas  (e.g.,  some recreational  fisheries).   Environmental agencies and health departments
 at  the  state  and  local  levels  have  responsibility  for  protecting  consumers  of local
 fisheries  products.    These   agencies  are  responsible  for  issuing  public health  advisories
and regulations related to local fisheries.

      Only  the  FDA  has  federal responsibility for  setting action  levels  and  tolerances
 for  concentrations  of  specific  chemicals  in  fish or  other  foodstuffs   that   constitute
sufficient health  hazards  to the general public to  require  that the  foodstuffs be removed
 from   interstate   commerce.     Action   levels  are   established  and   revised  according  to
criteria  in  the  code  of Federal Regulations  (21 CFR 109 and 509).  An  action level is
 revoked  when  a formal  tolerance for  the same  substance is  established.    In  developing
 action levels and  tolerances, FDA  takes  into account both  the magnitude  of  the  health
risks  to  consumers and the economic  impacts of  banning a  foodstuff  from a  particular
source.    FDA  sets  limits  on  chemical contaminants  in fisheries  products  to  achieve  an
optimal  balance  of health   protection  and  minimization of economic impacts  on  food-
 producing and harvesting industries (e.g., commercial fisheries and fish marketers).

      All action  levels  and  tolerances  to  date  have  been  developed  to  be  protective
 nationally,  rather  than on   a  regional  or local basis.   These national  standards  protect

                                             3

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the  average consumer of  a foodstuff,  assuming  the  consumer eats foods  from  a typical
"national  market  basket"  (U.S. FDA  1984).   For these  reasons,  it  has  been  stated  by
FDA that  action levels  and  tolerances are not  intended  to  protect certain consumers of
local fish  and  shellfish, such as local recreational fishermen whose consumption of  fish
from a  given  water  body may  exceed  the  national  average  (Taylor,  J.,  October 1986,
personal communication).

      EPA  and FDA  recognized  the need  to coordinate  their activities and  guidance in
assessing  health  risks  from   contaminated  fish   and   shellfish.    A   formal   interagency
mechanism  is  being created to resolve  potential  differences  in  risk  assessment  calculations
for  specific chemicals or  specific exposure  situations.   U.S.  EPA  and U.S.  FDA  (1987)
provides  a  detailed  discussion of   the  evolving   FDA/EPA  coordination  and procedures
whereby states  can  obtain  further information or  assistance  pertaining  to risk  management
in specific local situations.


Applicability of this Guidance  Manual

      EPA's  nonregulatory  technical  guidance, including this  manual  and  the 1986  final
guidelines  for  risk  assessment  (U.S.  EPA 1986a-e), is  available to  state and local govern-
ments responsible  for  fisheries  management.   This  manual  is  intended  for  use  as  a
handbook  by  state  and  local  agencies responsible   for  assessing potential   risks  from
local fish  or shellfish consumption.   For example, it  may be  useful  in assessing risks to
highly  exposed  regional  populations (e.g., certain fishermen  or  families  who  may  eat
unusually large amounts of fish) and in cases where  a national action level  or tolerance
has  not  been  defined  for a  chemical  that  is a local  pollution  problem.   This  manual
does  not provide  guidance on policy issues  that are  beyond  the  scope  of the technical
risk   assessment   process   (e.g.,  selection  of  acceptable  risk  levels,   and  methods   for
performing  local  cost-benefit  analyses).   Such   risk   management  decisions at  state  and
local levels are not ordinarily within the scope of federal  regulatory authority.

      For specific  technical assistance in applying the risk  assessment  methods  described
in this  manual,  users may call  the  EPA Office  of Water (see  Appendix A)  for updated
information  on  regional  EPA  facilities  that  can  provide on-site  assistance  in  applying
risk  assessment techniques.
Relationship of this Manual to Other EPA Documents

     This   manual  is  not  intended  as an exhaustive,  technically-detailed  guide  to all
aspects   of  sampling,   statistical  design,  laboratory   analysis,   exposure  assessment,  and
toxicological  risk  analysis.   Citations  are  provided  to references that  provide  details on
these topics.    In addition,  several  other EPA  documents  are  available  that  provide
relevant  information:

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           U.S. EPA (1987a) Integrated  Risk  Information  System  (IRIS)  Manual -
           A regularly updated  electronic database  on the toxicity and  carcinogenicity
           of individual chemicals (see Appendix B herein)

           Contaminants  in  Fish:   The  Regulation  and  Control  of  Residues  for
           Human Safety  [Report by the EPA  Risk Assessment Council  Subcommittee
           on  Fish Residue  Issues (U.S. EPA  and  U.S.  FDA    1987)].   This  report
           includes  a  discussion  of  the   relationships  of  EPA,  FDA,  and   state
           responsibilities for risk assessment and risk management.

           General  guidelines on exposure  and  risk assessment  (U.S.  EPA  1986a-e)
           discussed earlier.

           Guidance documents   on  risk  assessment  approaches  for specific chemicals
           [e.g., dioxins and dibenzofurans (Bellin  and Barnes 1986)].

           Superfund Risk  Assessment Information Directory (U.S. EPA 1986g).

           Risk  Assessment,  Management,  Communication:    A  Guide  to  Selected
           Sources  (U.S.  EPA  1987b) - A general  bibliography  which   is updated
           periodically.
Relationship of Fisheries Risk Assessment to Water Quality Criteria and Standards

      The  Criteria  and  Standards Division  of EPA's  Office   of  Water  Regulations  and
Standards  is  responsible   for  developing  water  quality   criteria  for  the  protection  of
aquatic life  and human  health.   Section 304(a) of  the Clean  Water Act  requires  EPA to
develop  recommendations  for  criteria  to be  used  by the  states  in setting water  quality
standards.   These  criteria are  summarized in "Quality Criteria for Water  -  1986"  (U.S.
EPA  1986h).   The technical  procedures for deriving human health  criteria for  water are
described in "Water Quality Criteria Documents; Availability" (U.S. EPA 1980b).

      Water quality criteria and  standards  are established  as  guidelines or legal  measures
for acceptable  concentrations  of  contaminants in  water.   State  agencies  and  EPA  use
water  quality  criteria and standards  to regulate discharges  of  contaminants  to   surface
waters.   In  contrast,  the  risk assessment approach described   in  this  document may  be
used  to  develop guidelines on  concentrations of  chemical  contaminants in  tissues  of fish
and  shellfish.    Data  on  tissue  concentrations of  contaminants are often used  by  state
health departments  in regulating human exposure  to  contaminated  fish  and shellfish,  or
in developing  health  risk  advisories  that  allow  sport fishermen  and  other frequent fish
eaters  to  adjust their own  consumption rates.   The  risk assessment  methods  described
in this manual  are consistent  with those used by  EPA  to develop  water  quality  criteria.
Moreover,  the  toxicological  and  epidemiological  data  used   to  establish  guidelines  for
concentrations  of  contaminants  in  fish  and  shellfish are  the  same  as  those used  to
develop  acceptable levels  in  water.    In  developing  water   quality  criteria,  U.S.  EPA
(1980b, 1986h) considered  human health  risks  from consumption of chemically contaminated
fish  and  shellfish.    For  each  chemical, a  bioconcentration factor  was  used  to establish
the  relationship  between   contaminant  concentrations  in  fish  and  shellfish  associated
with  three   "reference"  (i.e.,  benchmark) levels of  health  risk  (1(T5,   10'6,  1(T7)  and
corresponding  concentrations  of  contaminants in  water.   A  bioconcentration  factor  is
an empirically derived  measure  of the  potential  for a chemical  to accumulate  in  tissues

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of  aquatic  organisms.    Bioconcentration  factors  are   usually  expressed  simply  as  the
ratio of the chemical concentration in tissue to the concentration in  water.


Relationship of EPA Risk Assessment Methods to FDA Risk Assessment Methods

     Because  of  differences  in  legislative and  regulatory  responsibilities  among  EPA,
FDA, and state and local  governments,  these  entities have developed differing procedures
for risk  assessment and  risk  management.   As an  EPA guidance  manual,  this  document
presumes  the use of standard EPA risk assessment  procedures.  However, certain procedures
recommended  in  this  manual can be  modified  to  make the  risk  assessment compatible
with alternative  approaches used  by  FDA and some states.   This section  explains how
conversion factors  can be  used to  make  risk  assessment  procedures  recommended  herein
compatible with certain assumptions used in FDA risk assessments.

     A  major  difference  between  EPA  and  FDA  risk  assessment  approaches  concerns
the  methods  for  extrapolating  the  toxic  potency  of  chemicals  in   small  experimental
animals (e.g.,  rats  and mice)  to estimate  potential effects in  humans.   U.S. EPA (1986a)
pointed out several species-specific  factors that  may  influence the response  to a carcinogen,
including  life  span,  body  size,  genetic  variability,  concurrent diseases,  and  the  rates
and products of metabolism and excretion.  To  account  for at least some of the differences
between   experimental  animals  and   humans,  the  estimate  of exposure  in laboratory
animals is multiplied  by  a scaling  factor  to  obtain an  estimate of  equivalent  dosage in
humans.    EPA uses  the  ratio  of  animal-to-human surface  area, whereas  FDA uses  a
corresponding ratio of  body weights as a  scaling factor.  Thus, EPA uses mg of carcinogen
per  m2   body  surface  area  per   day as  a  standardized   scale for   expressing   dosages,
whereas  FDA  uses mg  carcinogen per  kg  body weight  per  day.    This  difference in
interspecies  extrapolation  factors results  in  approximately a five-  to  ten-fold difference
in estimates of carcinogenic potency (and risk) derived by the two agencies.

     In   recognition  of   the  difficulties  that  differences   in   interspecies   extrapolation
procedures between EPA  and FDA may pose  for state agencies and  others who  rely on
federal  guidance on risk  assessment,  EPA's Risk Assessment  Council  and FDA  reviewed
the pros  and  cons  of their respective methods for dosage  scaling.   They concluded  that
the most appropriate  method  for interspecies dosage  extrapolation  may  vary depending
on exposure  conditions.  For  example, one procedure  may  be more realistic for lipophilic
chemicals, whereas  the  other  would be more  appropriate  for  hydrophilic chemicals.
Differences  in  target organs  (i.e.,   primary   site  of   toxicity)  among  carcinogens  also
affects the preferred extrapolation procedure.

     Because  the  EPA extrapolation procedure  results  in a higher  estimate of risk than
the FDA procedure  (by  approximately an  order of magnitude), the  former is considered
more  protective.    For  most  EPA assessments,   the  surface-area  based  extrapolation  is
appropriate.   The  technical basis  for EPA's  approach  relies primarily  on a demonstrated
relationship between  pharmacological  effects  (e.g.,  balance  of  rates   of  metabolism  and
excretion) and body surface area  (Pinkel 1958; Freireich  et al.  1966;  Dedrick 1973).   If
state  or  local  policymakers  decide   that  the  body-weight  based extrapolation   is   more
appropriate  for  local risk  management  needs,  then   procedures  recommended  in  this
manual  can be  modified by converting  EPA's  dose-response data using a ratio  of human
body  weight  to surface  area.   This would  allow  the risk  assessor  to  use  carcinogenic
potency  factors  in EPA's  computerized   database,  IRIS (U.S.  EPA  1987a).   IRIS is   a
database  maintained  by  EPA to  provide regularly  updated  toxicological  data for use  in

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risk assessment.   The  use  of  IRIS  would  greatly  increase  the ability  of  a state  to
perform risk assessments for chemicals of local concern.

     Although  the  conversion of  EPA estimates  of toxic potency  to  estimates  based  on
equivalent dosage scales  related  to body  weight is  not technically complex,  the modified
procedure  should  preferably  be  carried  out  only by   experienced  toxicologists.    The
conversion  factor will vary  depending on  whether the  dose-response  data  were derived
from rats  or from  mice.  Thus the  original data set  must  be reviewed  to  determine an
appropriate  conversion  factor.   In  general, an  EPA  estimate   of  carcinogenic  potency
would  be  multiplied by  a factor equal to the  ratio of surface area per unit body  weight
(m2/kg)  of the  laboratory animal to that of humans.  For example, if the  EPA carcinogenic
potency  factor  is C and the surface area per  unit body weight  is  X for the laboratory
animal  and  Y  for  humans,  the corresponding  potency factor  based on  dosage scaled to
body weight is C  multiplied  by X divided  by  Y.  Because  specific data on surface  area
are  often  unavailable,  the body weight to the two-thirds power is typically  used  as an
estimate of  surface area.  Note that some EPA  carcinogenic potency  factors  are derived
from epidemiological studies and therefore do not require conversion.

     Other steps  in  the process  to  estimate carcinogenic potencies may  vary somewhat
among  regulatory agencies.   For  example, different  agencies  may choose  different data
sets  to  derive   a carcinogenic  potency  factor for  the  same  chemical.   The mathematical
expression used to  model  the dose-response relationship  may also differ  among agencies.
Hogan and Hoel (1982)  and  Cothern  et al.  (1986)  discuss various  models  for extrapolating
data from  high doses  used   in  laboratory  experiments to the  low  doses of  concern  in
carcinogenic risk  assessment.    At  low doses  corresponding  to risks  of  10"2  to  10"6  or
less, different   models  may  produce  results  that  vary by as  much  as several orders  of
magnitude.   Nevertheless, the  linearized  multistage procedure  used by  EPA  (U.S. EPA
1986a;  also see below,  Dose-Response Assessment)  yields results  that correspond  approx-
imately (within a  factor  of  two)  to  those  produced  by  the  linear model used  by FDA.
The interagency  Subcommittee  on  Fish   Residue  Issues of the  EPA  Risk  Assessment
Council,  which  includes  representatives  from  FDA,   concluded  that  the differences  in
procedures  for  modeling  dose-response relationships between EPA  and  FDA  were  small
relative  to  the  uncertainties  in  other steps  of  a risk assessment.  Therefore,  U.S.  EPA
(1987b) does not discuss procedures  to reconcile these differences.

     A  final distinction  between  EPA's  risk  assessment procedures  and  other potential
approaches  is   that EPA  does  not  yet  provide  a standardized   approach  for assessing
carcinogenic effects  on  children  and  fetuses.   Information  on peri-natal carcinogenicity
is presently being developed by EPA and others.

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            OVERVIEW OF RISK ASSESSMENT AND RISK MANAGEMENT


     As defined  earlier,  the objective  of risk assessment  is  to  estimate  the probability
of adverse health effects from  exposure  to a toxic  agent.  The elements of risk  assessment
and  their relationship to risk management are shown in Figure  1.   The following sections
provide  an  overview  of the steps  in risk assessment,  the  need for risk assessment, and
the  potential  uses of risk assessment of  chemically  contaminated  fisheries.   The  general
format  for  risk  assessment and  all definitions  of  terms used  in this report are consistent
with those provided  by National Research Council  (1983)  and U.S.  EPA (1984a-e,  1987a).
Background  information  on  food  safety  evaluation   by   federal  and  state  agencies  is
provided  by  U.S. Office  of  Technology  Assessment  (1979)  and  Food  Safety  Council
(1980,   1982).    Examples  of  approaches  used  by FDA  to  assess human health risks  from
toxic chemical  exposures  are described  in Cordle  et al. (1978) and Flamm  and Winbush
(1984).
MAJOR STEPS IN RISK ASSESSMENT

     A complete risk assessment includes the following steps:

     •     Hazard  identification:    Qualitative  evaluation  of  the  potential  for  a
           substance to cause  adverse  health  effects  (e.g.,  birth  defects, cancer)  in
           animals or in humans

     •     Dose-response  assessment:    Quantitative  estimation  of  the   relationship
           between  the  dose  of  a  substance  and  the probability  of   an adverse
           health effect

     •     Exposure  assessment:   Characterization  of  the   populations   exposed   to
           the toxic  chemicals of  concern;  the  environmental   transport  and  fate
           pathways; and the  magnitude, frequency, and duration of exposure

     •     Risk characterization:  Integration of qualitative and quantitative information
           from  the first three steps,  leading  to  an estimate of  risk for the  health
           effect of concern.

Because  uncertainties  are pervasive  in  risk  assessment,  uncertainty analysis  is  a  key
element  of  each  stage  of  the  assessment  process.   Assumptions  and   uncertainties  are
summarized  in  the  risk  characterization  step.    The  risk characterization  includes   a
balanced discussion of the strengths and weaknesses of the data presented.


NEED FOR RISK ASSESSMENT APPROACH

     Direct  measurement of human  health  risks  is  possible  in  certain limited  circum-
stances.   Such   circumstances  generally  involve  a  single  high  exposure  or  repeated
moderate  exposures of humans to a  specific chemical  with  a clear  adverse effect.   For
example,  direct  measurement  of  the  incidence  of chloracne (a  skin disorder)  might  be

                                               8

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     u
     N
     C
     E
     R
     T
     A
     I
     N
     T
     Y

     A
     N
     A
     L
     Y
     S
     I
     S
     HAZARD
   ASSESSMENT
 DOSE-RESPONSE
   ASSESSMENT
    EXPOSURE
   ASSESSMENT
      RISK
CHARACTERIZATION
MONITORING
        L_
   ANALYSIS OF
CONTROL OPTIONS
                MANAGEMENT
                  DECISION
                     A
• ECONOMICS

• POLITICS

•LAW

• SOCIAL
               IMPLEMENTATION
                OF CONTROLS
     L.
      J
                A
                S
                S
                E
                S
                S
                M
                E
                N
                T
M
A
N
A
G
E
M
E
N
T
        Figure 1.  Overview of risk assessment and risk management

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possible  in a  population  of  workers exposed  to a  polychlorinated biphenyl  (PCB)  spill.
In  contrast,  it  is  virtually  impossible  to  directly  measure  the incidence  of  cancer
associated  with  consumption  of  chemically  contaminated  fish  or shellfish.    The   long
latency  period   for  cancer,  the  potential  for  contamination  of  fisheries   by  multiple
chemicals,  and  confounding exposures through  other routes  would complicate  the  inter-
pretation  of  such data.    Mathematical  models  are  therefore  used by  EPA,  FDA,  the
Agency  for  Toxic Substances and Disease Registry, states and, other  regulatory  agencies
to estimate human health  risks  from  exposure  information.    Risk assessment  procedures
discussed  in  this manual  focus  on  estimating  potential  health  risks   from  long-term
exposure  to  relatively  low levels  of  contamination.   This  prospective  approach  is  also
useful for developing  regulations to  prevent  exposure  to  toxic chemicals and  associated
risks.

      Scientific  knowledge  of  the effects  of  toxic  chemicals  on humans  is  still  rudimen-
tary.   Much  of the  present  information  is  extrapolated  from  results  of laboratory  tests
on  animals  (e.g.,  rats and  mice).   Animal  test   data  are   used  to  estimate   levels  of
chemical  exposure  that  are   unlikely  to  cause  toxic  effects  in  human  populations.
Toxicologists  are  thus  faced  with many  uncertainties  when  estimating  the  potential  for
human health risks associated  with intake of toxic chemicals.   Despite  these  uncertainties,
regulatory  decisions  must   be  made.   Many  assumptions and  subjective judgments  may
enter into an  evaluation  of  human  health  risk.   The  risk  assessment  approach  provides
a  framework  for  consistent,  systematic estimation   of health  risks, with  clear  statements
of assumptions and uncertainties.

      The  risk  assessment  framework  offers an alternative to  some  common  approaches
to evaluation of data on  chemical  residues  in  fish  and shellfish.  As  noted  by  Kneip
(1983) and Peddicord  (1984), many  investigators have evaluated chemical residue data in
light  of human  health  concerns  simply  by comparing  tissue  concentrations of selected
chemicals  to  action   levels or  tolerances  established  by  U.S.  FDA  (1982,   1984).    This
approach is limited for the following reasons:

      •    FDA  limits are available for only a  few chemicals (mercury and approxi-
           mately  13 organic compounds).

      •    FDA  has  not  established  regulatory  limits for  some of the  most potent
           suspected   human  carcinogens   (e.g.,  2,3,7,8-tetrachlorodibenzodioxin)  or
           for some  of the common  contaminants in surface  waters (e.g.,  polynuclear
           aromatic hydrocarbons and most heavy metals).

      •    Action  levels and tolerances  were  intended to be used only for regulation
           of interstate commerce of food products.

      •    When  setting regulatory  limits,  FDA  considers economic impacts  of food
           regulation  as  well  as  the  potential  human  health  risks  on  a  national
           basis  (U.S. FDA  1984).  When using FDA limits to interpret bioaccumulation
           data,  investigators  implicitly  adopt  economic  policies  of FDA.    Thus,
           risk management issues are not clearly  separated from risk assessments.

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Use  of  regulatory  limits  on   toxic  chemicals  in   food  products  established  by  other
countries (Nauen 1983)  would  suffer from many of  the  limitations listed above for FDA
values.   Moreover, a concise review of the basis for each of these limits is not available.


USES OF RISK ASSESSMENT

     Risk assessment  may  be  applied  to  data on chemical residues in fish and shellfish
for the  following purposes:

     •     Identify and rank toxic chemical problems in specific  locations

     •     Develop   environmental  criteria  or  guidelines  at  the  national,   state,
           regional, or local level

     •     Develop public information and advisories.

The  first  two  applications  fall  within  the  general  category  of  regulatory  decision-
making.  In  this context, one  goal  of  EPA  is  to  define, identify,  and set priorities  for
reducing  unacceptable risks.  Risk assessment and  management provide  a  framework  for
balanced  analysis of environmental  problems  and consistent  policies for reducing health
risks  (e.g.,  through  reduction  of  toxic  pollutant   discharges  and  cleanup   of  polluted
areas).

     Risk  assessment can  be   used  to  identify and  rank  environmental  problems  in
several  ways.   First,  contaminated  sites  can  be  ranked  according  to the  relative risks
associated  with  consuming  fish and  shellfish  harvested  nearby (e.g.,  Versar   1985).   Site
rankings  may  be  used   to  establish priorities  for   investigation  of  contaminant  sources
and  for cleanup.  Maps  of chemical residue  data or risk estimates  provide a  geographic
overview of  the condition  of  harvested  resources.    Second, priority  chemicals  can   be
identified  according  to associated  health risks (e.g.,  Ames et al.  1987).  Finally,  various
fishery  species  and  weight  classes  within  species  can  be ranked  according  to  relative
risks.

     Risk  assessment  is  an  important  analytical  tool  for  developing  environmental
criteria  and  guidelines.  For  example, water quality  criteria derived by U.S. EPA  (1980b)
are based  in  part on human  health risk assessment.   FDA uses quantitative  risk assessment
to estimate  potential  human  health  risks,  which  are  considered  together  with  economic
factors  in developing action  levels  for chemical  contaminants  in fishery  products  (U.S.
FDA  1984).   Risk  assessment  models  can  be  used to  develop  guidelines on  maximum
advisable contaminant concentrations  in recreationally harvested species.   Such  guidelines
can  contribute  to  development of  target  cleanup  criteria established  to develop remedial
actions  for contaminated sites.

     The results of  risk  assessments  may  be used to inform the public about the  relative
health  risks of various fishery  species and geographic locations.   Providing the recreational
public  with such  information  allows  for individual choice  in  determining harvest area,
target species,  consumption rates,  and  other  factors  based on relative  risk.   Furthermore,
risk  assessment may  contribute  to  management  decisions by   federal,  state,  and local
agencies, which may  include:
                                               10

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      •    Investigating sources of pollution

      •    Reducing exposure potential by implementing pollution controls

      •    Restricting fishery harvests by geographic area or by species

      •    Issuing public  advisories or controls to limit:

                Geographic area of harvesting
                Harvest season
                Harvest methods
                Species harvested
                Catch  number
                Size range harvested
                Consumption rate.

      Further  information on the relationship between  risk assessment and risk  management
may  be  found  in  U.S. EPA (1984),  Ames et al.  (1987), Lave (1987),  Russell  and Gruber
(1987), and Travis et al. (1987).
                                               11

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                               HAZARD IDENTIFICATION
      The  first  step  in  the risk  assessment  process  is  to  define  toxicological  hazards
posed  by  the  chemical  contaminants  in  samples of  fish  and  shellfish.   These  hazards
are  summarized  in  a  toxicity  profile  or IRIS  chemical  file  for  each  contaminant  of
concern.   The  results  of  the  hazard  assessment  influence  the  nature  and  extent  of
subsequent steps  in risk analysis.  For example, the  endpoint of concern in dose-response
assessment may be  selected  based on  the most severe  adverse  effect  identified  in  the
hazard  assessment.    In  the absence  of  quantitative  data  for other  steps  in  the  risk
assessment process, the  hazard  assessment constitutes  the final  product for  a qualitative
evaluation of risk.
CONTAMINANTS OF CONCERN

     The  contaminants  of  concern to be  included  in a  particular  risk  assessment should
be selected based on the following criteria:

     •     High persistence in the aquatic environment

     •     High bioaccumulation potential

     •     High  toxicity to  humans  (or  suspected high  toxicity to  humans based  on
           mammalian bioassays)

     •     Known sources of contaminant in areas of interest

     •     High  concentrations  in  previous samples  of fish or  shellfish  from  areas
           of interest.

General   information  on  persistence,  bioaccumulation  potential,   and  toxicity  may  be
obtained  from  references  such as   Lyman  et  al. (1982)  and  Callahan  et  al.   (1979).
Other  key  sources that are  periodically updated  are the  Registry of  Toxic  Effects  of
Chemical Substances  (e.g., Tatken  and  Lewis  1983)  and  the  Annual Report  on  Carcino-
gens  (e.g.,  National  Toxicology  Program  1982).   Specific information   that  is  directly
useful  in risk assessment should be  obtained from  IRIS  (see below,  Sources  of  Informa-
tion  and Appendix B).

     Recommendations  regarding  specific  contaminants  of concern  are beyond the  scope
of this  guidance  manual.  A general  list of  contaminants  with available  EPA  toxicological
indices  [Reference Dose (RfD)  or  Carcinogenic Potency Factor] listed  in  IRIS is  provided
in Appendix  B.    The procedures  for quantitative  risk assessment outlined  in  this manual
are designed for use only with chemicals having  toxicological indices.  The bioaccumulation
potential  of  various  chemicals  is   a   key  consideration  in   selecting  contaminants  of
concern.   EPA  priority-pollutant  organic  chemicals   and  selected  pesticides are  listed  in
Table  1  in  descending  order  of  bioaccumulation  potential,  according  to their  octanol-
water  partition coefficients  (Tetra Tech  1985a).  Note  that  organic compounds with  a
log  octanol-water  partition  coefficient  greater  than  or  equal   to  2.3 were recommended

                                               12

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TABLE 1.  ORGANIC PRIORITY POLLUTANTS AND 30I(h) PESTICIDES RANKED
     ACCORDING TO OCTANOL-WATER PARTITION COEFFICIENTS (Kow)
                     (updated from Callahan et al. 1979)

Priority
Pollutant No.
69
83
89
79
111
__r
75
74
82
107
73
91
92
90
110
129
94
106
72
112
76
93
99
53
9
100
101
39
84
41
64
40
20
81
98
78
109
80
__r
52
66
68
Substance
di-n-octyl phthalate
indeno( 1 ,2,3-cd)pyrene
aldrin
benzo(ghi)perylene
PCB-1260
mirex
benzo(k)fluoranthene
benzo(b)fluoranthene
dibenzo(a,h)anthracene
PCB-1254
benzo(a)pyrene
chlordane
4,4'-DDT
dieldrin
PCB-1248
TCDD (dioxin)
4,4'-DDD
PCB-1242
benzo(a)anthracene
PCB-1016
chrysene
4,4'-DDE
endrin aldehyde
hexachlorocyclopentadiene
hexachlorobenzene
heptachlor
heptachior expoxide
fluoranthene
pyrene
4-bromophenyl phenyl ether
pentachlorophenol
4-chlorophenyl phenyl ether
2-chloronaphthalene
phenanthrene
endrin
anthracene
PCB-1232
fluorene
methoxychlor
hexachlorobutadiene
bis(2-ethylhexyl)phthalate
di-n-butyl phthalate
log(Kow)
8.06
7.66
7.40
7.05
6.91
6.89
6.85
6.60
6.50
6.48
6.42
6.42
6.36
6.20
6.11
6.10
6.02
6.00
5.91
5.88
5.79
5.69
5.60
5.51
5.47
5.44
5.40
5.22
5.18
5.08
5.00
4.92
4.72
4.57
4.56
4.54
4.48
4.38
4.30
4.28
4.20
4.13
Reference
m

0
i
d
b


k
d
i
i
n
0
d
i
i
a
j
d
j
h

d
k
d
d
j
h
g
d
g
g
h
d
h

d
b
f
d
m

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TABLE 1.  (Continued)
77
67
108
8
12
1
102
103
104
--•
7
105
21
95
96
97
49
26
25
27
55
113
38
62
22
31
28
37
58
--•
60
6
42
85
11
34
87
15
47
32
86
--•
14
24
50
4
51
35
36
33
30
acenaphthylene
butyl benzyl phthalate
PCB-1221
1 ,2,4-trichlorobenzene
hexachloroethane
acenaphthene
alpha-HCH
beta-HCH
delta-hexachlorocyclohexane
parathion
chlorobenzene
gamma-HCH
2,4,6-trichlorophenol
alpha-endosulfan
beta-endosulfan
endosulfan sulfate
fluorotrichloromethane (removed)
1 ,3-dichlorobenzene
1 ,2-dichlorobenzene
1 ,4-dichlorobenzene
naphthalene
toxaphene
ethylbenzene
N-nitrosodiphenylamine
para-chloro-meta cresol
2,4-dichlorophenol
3,3'-dichlorobenzidine
1 ,2-diphenylhydrazine
4-nitrophenol
malathion
4,6-dinitro-o-cresol
tetrachloromethane
bis(2-chloroisopropyl)ether
tetrachloroethene
1,1,1- trichloroethane
2,4-dimethylphenol
trichloroethene
1 , 1 ,2,2- tetrachloroe thane
bromoform
1 ,2-dichloropropane
toluene
guthion
1,1, 2- trichloroethane
2-chlorophenol
dichlorodifluoromethane (removed)
benzene
chlorodibromomethane
2,4-dinitrotoluene
2,6-dinitrotoluene
1 ,3-dichloropropene
1 ,2-trans-dichloroethene
4.07
4.05
4.00
3.98
3.93
3.92
3.85
3.85
3.85
3.81
3.79
3.72
3.69
3.60
3.60
3.60
3.53
3.48
3.38
3.38
3.36
3.30
3.15
3.13
3.10
3.08
3.02
2.94
2.91
2.89
2.85
2.64
2.58
2.53
2.47
2.42
2.42
2.39
2.30
2.28
2.21
2.18
2.18
2.16
2.16
2.11
2.08
2.00
2.00
1.98
1.97

b

k
b
b
P
P
h
e
d
h
c



c
k
k
k
h


b
a
a

g
d
e

d
g
b
b
b
b
b


b


b
c
d




c

-------
TABLE 1. (Continued)
--•
23
48
56
5
13
57
54
71
16
59
29
65
10
70
63
44
19
43
3
18
46
2
45
88
61

demeton
chloroform
dichlorobromomethane
nitrobenzene
benzidine
1,1-dichloroe thane
2-nitrophenol
isophorone
dimethyl phthalate
chloroethane
2,4-dinitrophenol
1,1-dichloroethene
phenol
1,2-dichIoroethane
diethyl phthalate
N-nitrosodipropylamine
dichloromethane
2-chloroethylvinylether
bis(2-chloroethoxy)methane
acrylonitrile
bis(2-chloroethyl)ether
bromomethane
acrolein (
chloromethane 1
vinyl chloride
N-nitrosodimethylamine

.93
.90
.88
.83
.81
.78
.77
.67
.61
.54
.53
.48
.46
.45
.40
.31
.30
.28
.26
1.20
1.12
1.00
3.90
3.90
3.60
3.58


b

b
g


b
b



a
b
b


g
g
b
b

b
t

g

• Veith et al. (1979a).
b Veith et al. (1980).
c Gossett et al. (1983).
d Veith et al. (1979b).
' Kenaga and Goring (1980).
f Leo, A., 20 November 1984, personal communication.
« U.S. EPA (1980).
h Karickhoff (1981).
' Rapport and Eisenreich (1984).
J Miller et al. (1985).
k Means et al. (1980).
1 Miller et al. (1984).
mMcDuffie (1981).
n Chiou et al. (1981).
0 Briggs (1981).
P Solubilities of the various isomers of HCH indicate that they will have
  similar log(Kow) values.
*> Estimated according to the procedure described by Chiou et al. (1982).
r Chlorinated 301(h) pesticides that are not on the priority pollutant
  list.
• Organophosphorus 301(h) pesticides that are not on the priority
  pollutant list.
NA » not applicable.

-------
by Tetra  Tech  (1985a)  for inclusion  in  EPA Section 301(h)  monitoring programs.   EPA
priority-pollutant  metals  are  listed  in  Table 2  in  descending  order  of  bioaccumulation
potential, according to bioconcentration  factor (Tetra Tech 1985a).

      Screening of  potential contaminants  of concern  should  be done on  a  case-by-case
basis during preparation of risk assessments.  When data on concentrations  of  contaminants
in  edible  tissues of  fishery organisms are  available,  preliminary  calculations  of  potential
risks may  be  made  to rank  chemicals  by  relative  priority  for  detailed  evaluation.   If
contaminant concentration  data are available for  soils,  air,  and  water (at  a hazardous
waste  site, for example),  U.S. EPA (1986f)  methods  for selecting  indicator chemicals  for
public health evaluations at Superfund  sites may be used to gain perspective  on  contaminants
of concern.  For  potential  carcinogens, the qualitative weight of evidence for carcinogenicity
should be  considered.  Those chemicals with sufficient evidence of carcinogenicity in humans
should generally be considered as contaminants of concern.


TOXICITY PROFILES

      Toxicity   profiles  are  summaries  of  the  following   information  for  the  selected
chemicals of concern:

      •    Physical-chemical properties (e.g., vapor  pressure,  octanol-water partition
           coefficients)

      •    Metabolic  and   pharmacokinetic   properties (e.g.,  metabolic  degradation
           products, depuration kinetics)

      •    Toxicological  effects    (e.g.,  target  organs,  cytotoxicity,  carcinogenicity,
           mutagenicity) according to specific uptake route of concern (i.e., ingestion).

A toxicity profile may  consist  of  an  IRIS  chemical  file.   An  example  file  taken- from
IRIS is provided in Appendix B.

      The  key  elements of a  hazard  identification should be  summarized  in a concise
tabular format.   The  examples  shown in Table 3  and in  the first  two  sections of  the
IRIS  file  (Chronic  Systemic  Toxicity;  Risk Estimates for Carcinogens)  in  Appendix B
illustrate   the  kinds  of  information  used   to  evaluate  toxicological  hazards.   Neither
toxicity profile in Table 3 is intended to be comprehensive.

      Information in a toxicity profile  is used  to  support  the  weight  of evidence classifi-
cation for  the likelihood  of  a chemical  causing a  given  health  effect.   The  endpoints
considered  should include  noncarcinogenic  as  well   as  carcinogenic  effects.    EPA  has
developed   a  weight-of-evidence   classification  scheme   which  indicates  the   potential
carcinogenicity of chemicals (U.S. EPA  1986a; 1987a).  It includes the following categories:

      •    Group A  -  Human Carcinogen:   This group  is  used only  when  there is
           sufficient  evidence  from   epidemiologic   studies  to  support  a   causal
           association between  exposure to the agents and cancer.

      •    Group B  - Probable Human Carcinogen:   This  group includes  agents  for
           which  the  weight  of evidence  of human  carcinogenicity  based on epi-
           demiologic  studies  is  "limited."   It  also includes  agents  for  which   the

                                               13

-------
  ALPHABETIC LISTING OF CHEMICALS ON IRIS  (03/31/87)
     67
     79
  15972
    116
    3O9
    107-
 2O859-
  7773
  7440
 74115-
  7440-
    542
 43121-
 68359-
  1861-
 17804-
 25057-
    92
    50
  7440
    92
   117
   111
    74
  1689
   106
    71
    85
  7440-
   592
   133
    63
    56
 55285-
 5234-
   133
    57
  506
    67
 1897
 2921
64902-
16065
 7440
  544-
 -64-1
 -10-7
 -60-8
 -O6-3
 -00-2
 -18-6
 -73-8
 -06-0
 •36-0
 •24-5
 •39-3
  62-1
  43-3
 •37-5
 -40-1
 -35-2
 -89-0
 -87-5
 -32-8
 -41-7
 -52-4
 -81-7
 -44-4
 -83-9
 -99-2
 -99-0
 -36-3
 •70-1
 •43-9
 -01-8
 06-2
 •25-2
 23-5
 14-8
-88-4
-90-4
-74-9
-77-4
-66-3
-45-6
•88-2
-72-3
 83-1
 47-3
 92-3
21725-46-2
   57-12-5
  460-19-5
  127-20-8
39515-41-8
   94-82-6
   50-29-3
 1163 19-5
  Acetone
  Acrrlic Acid
  Alachlor
  Aldlcarb
  Aldrin
  Allyl  Alcohol
  Aluminum Phosphide
  Ammonium Sulfamate
  Antimony
  Apollo
  Barium
  Barium Cyanide
  Bayletoo
  Bajrthroid
  BeoefIn
  Benomyl
  Bentazon
  Benzldiae
 Beozo[a]pyrene (BaP)
 Beryllium
 1.1-Blphenyl
 Bi3(2-ethrlhexyl)phthlate (BEHP)
 Bl3(chloroethyl)ether (BOS)
 Bromomethane
 Bromoxynll Octanoate
 1.3-Butadiene
 n-Butanol
 Butylphthalyl Butylglycolata (BPBG)
 Cada>luai
 Calcium Cyanide
 Captan
 Carbaryl
 Carbon  Tetrachlorlde
 Carbosulfan
 Carboxln
 Chloramben
 Chlordane
 Chlorine Cyanide
 Chloroform
 Chlorothaloall
Chlorprrlfoa
Chlorsulfuron
Chroeiluai(III)
Chromlum(VI)
Copper Cyanide

Cyanazlne
Cyanide,  free
Cyanogen
Dalapon
Danltol
2,4 DB
DDT
Decabromodlphenyl Ether (DODPE)
   8065-48-3
     106-37-6
     84-74-2
     924-16-3
     75-71-8
     107-06-2
     75-35-4
     120-83-2
     94-75-7
     62-73-7
     55-18-5
  55290-64-7
     60-51-5
    120-61-6
  987B5-43-2
     62-75-9
  12345-67-8
     51-28-5
     88-85-7
    127-39-4
    122-66-7
     85-00-T
   298-04-4
   145-73-3
   106-89-8
   563-12-2
   141-78-6
   100-41-4
     84-72-0
 16984-48-8
 59756-60-4
   944-22-9
    64-18-6
 39148-24-8
   110-00-9
  1071-83-8
  1024-57-3
    87-82-1
    87-68-3
   319-84-6
   319-86-8
  6108-10-7
no CAS No.
   77-47-4
19408-74-3
   67-72-1
   74-90-8
 7783-06-4
35554-44-0
81335-37-7
   78-83-1
   78-59-1
33820-53-0
   58-89-9
  330-55-2
no CAS No.
  123-33-1
   Dave ton
   1,4 -DlbroBobenzene
   Dlbutyl Phthalate
   DSbuty Inl troaajnlne
   Dich1orod1f1uoro»«thane
   1,2-Dlchloroethane
   1.1-Dlchloroethylene
   2,4-Dichlorophenol
   2,4.-Dlchlorophenoxyacetlc acid  (2,4-D)
   Dlchlorvos
  Dlethylnltroaaaine
  DlMthipln
  DlMthoata
  Dlaethyl Tarephthalate
  DiMthyl doorknob (DMDK)
  Dimethylnitroaaaiine
  Dinitrochlckenwlre (DNCH)
  2,4-Dlnltrophenol
  Dlnoseb
  Diphenylaaine
  1,2-DlphenyIhydrazioe
  Dlquat
  Dlsulfoton
  Endothall
  Eplchlorohydrln
  Ethlon
  Ethyl Acetate
  Ethylbencene
  Ethylphthalyl Ethylglycolate  (EPEQ)
  Fluoride
  Flurldone
  Fonofon
  Formic Acid
  rosetyl-Al
 Furan
 Glyphoaata
 Beptachlor EpoxIda
 Hexabroarabenzane
 Rexachlorobutadlene
 alpha-Bexachlorocyclohexaae (alpha-BCB)
 delta-Hexachlorocyclohexane (delta-BCB)
 epsllon-Baxachlorocyclohexane (epslloo-BCH)
 Bexachlorocyclohexane,  technical (t-BCH)
 Bexachlorocrclopentadlene (HCCPD)
 Bexachlorodlbenzo-p-dloxln (UxCDD)
 Bexachloroethane
 Hydrogen Cyanide
 Hydrogen Sulflde
 iMzalll
 laiazaquln
 Isobutyl Alcohol
 Isophorone
 Isopropalln
 Llndane
 Llnuron
 Londajt
Halelc Hydrazlde
                                                                                                                       94-74-6   MCPA
      93-65-2
   57837-19-1
   16752-77-5
      75-09-2
      78-93-3

    108-10-1
  22967-92-6
    298-00-0
  S1Z18-45-2
  21087-64-9
    3OO-76-5
   1929-82-4
  14797-55-a
  10102-43-9
  14797-65-0
     98-95-3
  10102-44-O
     86-30-6
    621-64-7
  10595-95-8
    930-55-2
  27314-13-2
  32536-52-0
  19044-88-3
  23135-22-0
  42874-03-3
  76738-62-0
  1910-42-5
  32534-81-9
   608-93-5
    87-86-5
 52645-53-1
   108-95-2
   108-45-2
    62-38-4
   732-11-6
  7803-51-2
   151-50-8
   506-61-6
  1610-18-0
 23950-58-5
  1918-16-7
  709-98-8
  139-40-2
 51630-58-1
 13593-03-8
  7783-OO-8
  630-10-4
 74051-80-2
  7440-22-4
  506-64-9
26G28-22-8
  143-33 9
  148-18-5
   57-24 9
   MCPP
   Metalaxyl
   He thorny 1
   Methylena Chloride                  ,
   Methyl  Ethyl  Kxtooe (HER)

   Methyl  laobutyl Katone  (MIDK)
   Methyl  Mercury
   Methyl  Parathlon
   Metolachlor
   Metrlbuzln
   Haled
   Nltrapyrlo
   Nitrate
  Nitric Oxide
  Nitrite
  Nitrobenzene
  Nitrogen Dioxide
  N-NltrosodlphenylaaUne'
  H-Nltro9odl-N-propyla»lne
  N-Nltrosoawthylethrlaaiine
  N-Nltrosopyrrolldlna
  Norflurazon
  Octabroaxxiipheayl  ether
  Oryzalln
  Oxaayl
  Oxyfluorfen
  Paclobutrazol
  Paraquat
  PentabroaKxliphenyl  ether
  Pentachlorobenzene
  Pentachlorophenol
  Perawthrln
  Phenol
 •-Phenylanedlaailne
 Phenyl Mercuric Acetate
 PhosMt
 Phosphlne
 Potasslua Cyanide
 Potasaluai Silver Cyanide
 Proveton
 Pronaalde
 Propachlor
 Propan11
 Propazine
 Pydrln
 Oulnalphoa
 Selenioua Acid
 Selenourea
 Sethoxydla
Silver
Silver Cyanide
Sodiua> Azlda
Sodium Cyanide
Sodium DtnthyldlthlocarbaMte (Dlthlocarb)
Strychnine

-------
   TABLE 2.  INORGANIC PRIORITY POLLUTANTS RANKED
     ACCORDING TO BIOCONCENTRATION FACTOR (BCF)

Priority
Pollutant No.
115
118
119
119
123
124
127
114
117
121
124
125
126
Substance
arsenic
cadmium
chromium VI
chromium III
mercury
nickel
thallium
antimony
beryllium
cyanide
nickel (subsulfide, refinery dust)
selenium
silver
Log BCF*
2.544
2.513
2.190
2.104
2.000
1.699
1.176
ND
ND
ND
ND
ND
ND

11 BCF = Bioconcentraction Factor (U.S. EPA 1980b; Tetra Tech
       1985a).

ND •= No data.

-------
                          TABLE 3.  TOXICITY PROFILE FOR  MERCURY AND  PCBsa
          Property
          Mercury13
          PCBsc
CAS Number

Physical-Chemical

  Molecular Weight
  Vapor Pressure (mm Hg)
  Solubility (mg/L)
  Log Kowd

Log Bioconcentration Factord

Carcinogenic Status
Acute Toxicity

  Human (mg/kg body wt) LD50
  Mammal (mg/kg body wt) LDSO
  Aquatic (mg/L) LC50

Chronic Toxicological Effects

  Humans
  Mammals
  Aquatic Organisms
  Critical end point for
  risk assessment
7439-97-6
200.6-318.7
0.012-0.028
0.056-400,000
N/Ae

2.0-4.6

Noncarcinogen
29«
1.0-40.9
0.015-32.0
Motor and sensory impairment
leading to paralysis, loss
of vision and hearing, and
death. Kidney dysfunction.

Reproductive impairment and
teratogenic effects.

Developmental and structural
anomalies, suppression of
growth and reproduction,
impairment of behavior.

Central nervous system
effects (e.g., ataxia and
parathesia)h
1336-36-3
154.2-498.7
2.8 x lO'9 -  7.6 x lO'5
<0.001-5.9
4.0-6.9

1.9-5.2

Probable human carcinogenf
   Group B2
   — Sufficient animal evidence
   -- Inadequate human evidence
1,010-16,000
0.001-61.0
Skin lesions, liver dysfunctions,
and sensory neuropathy.
Hepatotoxicity, fetotoxicity, skin
lesions, and hepatocellular carcinoma

Reproductive and developmental
impairment.
 Hepatocellular carcinomaf

-------
TABLE 3.  (Continued)
* This is an example toxicity profile and is not intended to be comprehensive.

b  Mercury  may  occur   in   its  elemental  form,  as  inorganic   salts,   or   as   organic   complexes.
Consequently,   the   chemical    and   toxicological   properties   vary   tremendously   depending   on
the degree  of complexation or metal speciation.

c   Physical-chemical   properties   and   toxicity   vary   according   to   the   degree   of   chlorine
substitution, the number of adjacent unsubstituted carbons and steric configuration.

d Tetra  Tech (1985a).

' N/A » not applicable.

f EPA (1980a,b 1985a); IARC (1978).

*  For   mercury  (II)  choride  via  oral  route  of exposure  (Tatken  and  Lewis   1983).    Relevance
to consumption of mercury (primarily methylated) in fish  is questionable.

h Clarkson  et al. (1973).

-------
           weight of evidence  of carcinogenicity based on animal studies  is "sufficient."
           The  group is  divided into two  subgroups.   Usually,  Group Bl  is reserved
           for  agents for  which  there  is  limited  evidence  of  carcinogenicity from
           epidemiologic  studies.   It is  reasonable, for  practical  purposes, to regard
           an agent  for which there is  "sufficient" evidence  of  carcinogenicity in
           animals as presenting  a  carcinogenic  risk to humans.   Therefore, agents
           for   which there  is  "sufficient"  evidence  from  animal  studies  and  for
           which  there   is  "inadequate"  evidence or  "no  data"  from  epidemiologic
           studies would usually be categorized under Group B2.

     •     Group  C  - Possible  Human  Carcinogen:  This group  is  used for agents
           with  limited  evidence of  carcinogenicity  in  animals in  the absence of  data
           on humans.   It  includes  a  wide variety  of evidence;  e.g., (a)  a malignant
           tumor  response   in  a  single,  well-conducted  experiment  that does  not
           meet conditions for sufficient  evidence;  (b)  tumor  responses  of marginal
           statistical  significance  in  studies  having inadequate  design or reporting;
           (c) benign but  not  malignant tumors  with  an  agent  showing  no response
           in  a  variety  of short-term  tests  for mutagenicity; and  (d)  response of
           marginal  statistical  significance  in  a tissue  known  to  have  a  high or
           variable background rate.

     •     Group  D  - Not Classifiable  as to Human Carcinogenicity:  This group  is
           generally  used for  agents  with  inadequate human  and  animal  evidence of
           carcinogenicity or for which no data are available.

     •     Group  E  - Evidence of  Noncarcinogenicity for Humans:   This  group  is
           used  for agents  that show no evidence for carcinogenicity in  at least  two
           adequate animal tests in different species or in  both adequate epidemiologic
           and  animal studies.   The classification of an agent in  Group  £  is based
           on the  available evidence and  should  not  be  interpreted as  a definitive
           conclusion  that the agent is not a carcinogen under any circumstances.

The  above  descriptions for  the categories  were  taken  from   U.S.  EPA  (1986a).    At
present,  a  weight-of-evidence classification  for carcinogenicity  is  available  in  IRIS  for
each chemical assigned a Carcinogenic Potency  Factor.


SOURCES OF INFORMATION

     In  many  cases, EPA regions   and others  may  rely on  toxicity profiles  generated
previously.   IRIS  is  a  key source  of  chemical  toxicity  data,  including  information from
critical  studies  and  weight-of-evidence classifications  for  carcinogens.    The   first  step
in a hazard assessment  should  be  to consult  IRIS chemical files for  potential  contaminants
of concern.  IRIS chemical  files  will  be available for  approximately 270  chemicals  by
November 1987.  Further information on  IRIS is provided in Appendix B.

     The  primary  sources  of toxicity  profiles  are  the  EPA  Office  of Waste  Programs
Enforcement  and  Office  of  Health  and  Environmental  Assessment  (e.g.,  Appendix  C,
Table  C-l).    EPA  toxicity  profiles   are   available   for  approximately  195   chemicals.
Additional sources are shown in Appendix C,  Table  C-2.  Under the Superfund Amendments
and  Reauthorization  Act of  1986, EPA  and  the  Agency for  Toxic  Substances and  Disease


                                               14

-------
Registry are preparing  toxicity profiles for  100  hazardous substances considered as  high
priority contaminants at Superfund sites.

     Supplementary  information  on   the  toxicity  of  contaminants  of  concern  may be
obtained from  bibliographic  or  chemical/toxicological databases.  DIALOG, a comprehensive
bibliographic database  system  (Dialog  Information  Services, Inc.,  3460  Hillview Avenue,
Palo Alto, CA   94304),  offers access to databases such  as  Pollution Abstracts, National
Technical Information Service,  and  ENVIROLINE.  Chemical  and toxicological  information
can be obtained from the databases listed in Appendix C, Table C-3.
                                              15

-------
                            DOSE-RESPONSE ASSESSMENT


     After  the potential hazard  associated with  each contaminant  of concern  is charac-
terized, the  relationship  between dose  of a  substance  and its biological effect is  deter-
mined.   Dose-response  data  are  used  to  determine  the  toxicological  potency  of  a sub-
stance, a  quantitative  measure  of   its  potential  to  cause a  specified  biological  effect.
The  concepts of exposure, dose, dose-response relationship,  and toxicological potency  are
discussed in the following sections.


EXPOSURE  AND DOSE

     The concepts of exposure and dose, as defined below, are central to risk assessment:

     •     Exposure:  Contact by an organism with a chemical or physical agent

     •     Dose:  The  amount  of chemical uptake  by  an organism  over a specified
           time as a consequence of exposure.

The  "ingested   dose,"  or  amount  of  chemical  ingested,   is distinct  from  the  "absorbed
dose."   For  the oral  route of  exposure,  the absorbed  dose  is the  amount  of  chemical
assimilated by  absorption  across the  lining of the  gastrointestinal  system.   Exposure  level
or exposure  concentration  is used  to  denote  the  concentration (mg/kg wet  weight) of
contaminant  in  edible  tissue  of fish  or shellfish.   As shown  below,  the absorbed dose  is
estimated  from  food  consumption   rate,   the  exposure  concentration, and  an  absorption
coefficient (see Exposure Assessment).


DOSE-RESPONSE RELATIONSHIPS

     The  form of  the  dose-response  relationship  for  carcinogens  is assumed  to  be
fundamentally   different from  that  for  noncarcinogens  (U.S.  Office   of  Science   and
Technology  Policy 1985).   Examples of  general  dose-response  relationships are  shown in
Figure 2.  The  lack  of a demonstrated  threshold  in  dose-response  relationships  for  car-
cinogens (U.S.  EPA  1980b,  1986a;  U.S.  Office  of  Science  and  Technology  Policy  1985)
implies a finite risk of cancer  even at very  low doses of the carcinogen.
For  noncarcinogenic  effects,  there  is usually  a  threshold dose, i.e.,  a dose  below which
no adverse   biological  effects are observed  in  the  animal bioassay.   The  threshold  dose
is  termed the  No-Observed-Adverse-Effect-Level (NOAEL), as shown in Figure  2.   Note
that  a  nonzero  mean response may  be a  NOAEL if that mean response is not significantly
different  from  zero  as determined  by a statistical  test.   The  Lowest-Observed-Adverse-
Effect-Level (LOAEL)  is the lowest concentration  that results  in  a  statistically significant
health effect in the test population.

     A  measure  of  toxicological  potency  is  derived  from  an  empirical  dose-response
relationship  for the  chemical  of  interest.    Toxicological potency  indices  for  two  broad
categories of toxicants are defined as follows:


                                              16

-------
 Crt
 oe
 o
 o
o
Ul
o
UJ
oc
          LOW-DOSE
          REGION Of
          CONCERN
                DOSE  OF  CARCINOGEN
                                   OBSERVED DATA  POINTS

                                        • CHEMICAL A
                                        A CHEMICAL B
                                        • CHEMICAL C


                                            MODELS	

                                   — —- — Low dose
                                          extrapolation

                                   —— Models fit within
                                          observed data range
U
LU
Z X
o
u
oc
        Rfd
         •»••• UF
NOAEL
                                                      Frequency -   Proportion of
                                                                  animals tested

                                                           RfD •   Reference Dose
   UF.   Uncertainty Factor

NOAEL .   No Observed
         Adverse Effects
         Level

  Dose •   Ingested Dose
              DOSE  OF  NONCARCINOGEN
         Figure 2  Hypothetical example of dose-response curves for a
                   carcinogen and a noncarcinogen.

-------
     •     Carcinogens  are   individually  characterized  by  a  Carcinogenic  Potency
           Factor,  a  measure of the cancer-causing potential of a substance estimated
           by the  upper 95  percent confidence  limit of  the slope of  a straight line
           calculated  by the linearized  multistage  procedure  or  another appropriate
           model

     •     Noncarcinogens  are  individually  characterized  by  an  RfD, an  estimate
           (with  uncertainty  spanning  perhaps an order  of magnitude)  of the daily
           exposure  to  the  human  population   (including  sensitive  subpopulations)
           that  is  unlikely to produce  an appreciable risk  of adverse  health  effects
           during a lifetime.

Carcinogenic Potency  Factors are also  referred to as Slope Factors.   RfDs  are  conceptually
similar to Acceptable Daily Intakes (U.S. EPA  1987a).

     The  data  set  used to  define  toxicological  indices  is  determined  by the quality of
available  data,  its relevance to modes of  human  exposure, the  similarity of  the  species
to humans, and  other technical factors.   Adequate data from clinical or epidemiological
studies  of  humans are preferred  over animal  data.    If  adequate human  data  are not
available, a data  set for the  animal  species most  similar  to humans or for the most sensitive
species  is  used  in  the  dose-response  assessment.   Data  are evaluated  by EPA to ensure
high quality (e.g., U.S. EPA 1980b, 1985a).

     The  main  source  of dose-response data  for deriving Carcinogenic  Potency  Factors
and  RfDs  is lifetime  cancer bioassays performed on  rats or mice.   Because  most of  these
experiments  are  designed  to  be   cost-effective,  doses   in  bioassays  may  be  orders  of
magnitude above those  encountered in the  human environment.   High  doses  are  used  in
laboratory  bioassays  for several  reasons:  1)  to reduce  the  time  required  to produce  a
response  and  thus overcome  problems  related  to latency period  (i.e.,  length  of  time
between exposure  and  appearance  of health  effects),  2)  to  obtain  sufficient  statistical
power  to  detect  health  effects,  and  3)  to decrease  the absolute  number  of   animals
required and  thereby  reduce costs.  Doses  in  animal  bioassays  for  oral  uptake of  con-
taminants  are   usually  the   administered  (ingested)  dose,  not   the  absorbed  dose  (i.e.,
uptake across the lining of the gastrointestinal  system).

     Carcinogenic  Potency  Factors  and  RfD values  derived  by EPA  are  listed  in the
IRIS  database.   At  present, values for these toxicological  indices  are  being  standardized
for agency-wide  use.   A brief overview of methods by which  these  indices  are  derived
is presented below.
CARCINOGENIC POTENCY FACTORS

     The  Carcinogen Assessment Group of  EPA currently uses the  linearized  multistage
procedure  to  derive  Carcinogenic  Potency  Factors  (U.S.  EPA   1980b,   1985a,   1986a,
1987a).   The  multistage  model  assumes  that   carcinogenesis   results  from  a  series   of
interactions  between  the  carcinogenic  chemical   and  DNA, with  the  rate  of interactions
linearly  related to  dose.   For example,  a  chemical  may  induce a  mutation in the  DNA
of  a cell  to  initiate carcinogenesis.  However,  a series  of further  interactions  between
DNA  and  the same chemical  (or  another  one) may be necessary  to  promote  carcino-
genesis and  induce  a tumor.   The  multistage model  is  the model most  frequently used
by  EPA  when there is  no convincing  biological  evidence to  support  application  of  an

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alternative  model.   Other  models  include  the  logit,   probit,  single-hit,   and  Weibull
models (Food Safety Council  1980, 1982; Hogan and Hoel 1982; Cothern  et  al. 1986).   At
high  doses (corresponding  to  lifetime  risks greater than  about  10~2), all  currently  used
models yield generally  similar  risk  estimates.   Below risks on  the  order  of  10'2,  the
models diverge  increasingly  as  dose  declines.   In  the   low-dose  range,   the  linearized
multistage model generally predicts risks  similar  to  the  single-hit  (i.e.,  linear)   model.
For  many data  sets,  both  of these models  yield  higher  estimates  of low-dose  risk  than
do  other   models (U.S.  EPA   1980b;  Hogan and Hoel  1982; U.S. Office  of  Science  and
Technology Policy 1985).  The mathematical form  of  the  multistage  model for a  specified
carcinogen is:

                R(d) «  1 - exp [-(Qid +  q2d2 + ...  + qkdk)]                                (1)

where:

       R(d) - Excess lifetime risk of cancer (over background at dose d)
              (dimensionless)
   q{ values = Coefficients [kg day mg"1  (i.e., the  inverse of dose units)]
          d * Dose (mg kg'1 day'1)
          k » Degree of the polynomial used in the multistage model.

     U.S. EPA (1987a) described  the linearized multistage procedure as  follows:

     •    The multistage model is fitted to  the data on tumor incidence vs. dose

     •    The  maximum  linear  term consistent  with the  dose-response  data  is  cal-
           culated, which  essentially defines the linear portion  of the dose-response
           function at low doses

     •    The  coefficient  of the  maximum linear term, designated  as qt*, is set
           equal  to the slope of the dose-response function at low  doses

     •    The  resulting estimate of q/ is  used as an upper-bound  estimate of the
           Carcinogenic Potency Factor (termed Slope Factor in U.S. EPA 1987a)

qx* is  usually calculated  as  the  upper 95  percent confidence limit  of  the estimate  of
the coefficient  qx in  Equation  1.   Because the slope  of the dose-response function at
high doses could  be different from  that at  low doses,  the use  of qt* as an upper-bound
estimate of potency  is  not valid at high  exposures.   In  general, ql   should not be  used
as the upper-bound estimate of  potency at exposures corresponding  to  excess lifetime risks
greater than approximately 10~2  per individual  (i.e.,  one excess tumor  per  100  exposed
individuals).

     The  model  commonly used  to estimate plausible-upper-limit  risk  for  low  levels of
exposure over a lifetime is therefore:

                           R'(d) - QJ* d                                                (2)
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where:

      R*(d^ - Upper-bound estimate of excess lifetime risk of cancer (dimensionless)
        QI  - Upper-bound estimate of carcinogenic potency (kg day mg'1)
          d - Dose (mg kg'1 day'1).

Equation 2 represents a linear approximation of the multistage model.

     If a  potency  factor is derived from  nonhuman data,  as is  usually the case,  it must
be  extrapolated  to  humans.    Before  being  applied  to  humans,  Carcinogenic   Potency
Factors derived  from animal  data  are  corrected using  surface-area  differences   between
bioassay animals  and humans (U.S.  EPA  1980b,  1986a).  The rationale for using  surface-
area extrapolations  is detailed in Mantel  and Schneiderman (1975).  The relationship  between
surface-area  extrapolation  and  body-weight  extrapolation approaches  is discussed in  the
Introduction  above  (see Background, Relationship  of  EPA  Risk Assessment Methods  to FDA
Risk Assessment Methods).


REFERENCE DOSES

     Current methods for  predicting  human health  effects  from exposure  to  noncarcino-
genic chemicals rely  primarily  on the concept of  an RfD (U.S. EPA  1987a).  The RfD is
derived from  an observed threshold  dose  (e.g.,  NOAEL  or LOAEL  if  the NOAEL is
indeterminate)  in  a  chronic  animal  bioassay  by applying  an  uncertainty  factor, which
usually  ranges  from  1  to  1,000  (Dourson  and  Stara 1983).   The relationship between the
NOAEL,  the RfD, and  the  uncertainty  factor  are illustrated in  Figure  2  above.   The
uncertainty  factor  accounts for  differences  in  threshold  doses  among  species,  among
intraspecies groups  differing  in  sensitivity, and  among  toxicity  experiments of  different
duration.   Dourson  and  Stara  (1983)  and  U.S.  EPA  (1987a)   discuss the  methods  for
deriving RfDs  and  the criteria  for selecting uncertainty  factors.   In  brief, an uncertainty
factor  of  1000 is  based on  combining a factor of  10 to  account  for animal-to-human
extrapolation,  a  factor  of 10  to  protect sensitive  individuals,  and  a  factor of 10  to
account for use of a LOAEL in place of a NOAEL.


SOURCES OF INFORMATION

     In  many cases, EPA  regions  and  other  agencies will be able  to  rely  on  dose-
response  assessments  generated  previously.    Current  values for  Carcinogenic   Potency
Factors and  RfDs  are given in  IRIS  (U.S.  EPA 1987a; e.g., see  Appendix B).   Before
using  these  values,  investigators  should  consult  the  IRIS  database  and  current  EPA
health   assessment  documents for  information  on  their derivation  and  uncertainties  for
each chemical.  Contacts for information  on  specific chemicals are  listed in IRIS  Chemical
Files.
Carcinogenic Potency Factors

     The  Carcinogenic  Potency  Factors  calculated  by  the  EPA  Carcinogen  Assessment
Group are  published  in  IRIS and in each  health  assessment  document  produced  by the
Office  of  Health   and  Environmental Assessment (e.g.,  U.S. EPA  1985a).   The  EPA
Carcinogen  Assessment Group  determines  these  carcinogenic  potency values and  updates

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them periodically.    Before  being  entered into  IRIS,  Carcinogenic  Potency  Factors and
supporting documentation are  reviewed by the  Carcinogen  Risk  Assessment  Verification
Endeavor (CRAVE)  work group.   The list of Carcinogenic  Potency Factors  published  in
each  health  assessment  document  is  intended  only  to provide  comparative  information
for various  chemicals.  IRIS  should be  used as  the primary source  of Carcinogenic  Potency
Factors  for risk assessment.
Reference Doses

     IRIS  is  the  primary source of RfD  values.  An example of an  IRIS data sheet for
the pesticide  lindane  is  shown  in  Appendix B.  The data sheet provides information  on
the RfD,  the endpoints (biological  effects)  of concern,  experimental  data  sets, doses,
uncertainty  factors,   additional   modifying  factors,   confidence   in  the   RfD,  reference
documentation, and dates  of agency RfD reviews.

     Individual program  offices within EPA  may  need  to  be  consulted  for  information
on  chemicals   not yet incorporated  into  IRIS.   For  example,  the  Office  of  Drinking
Water  is a source of  RfDs  for  selected chemicals.   In  May 1987, the Office  of  Drinking
Water  released  draft  Health  Advisories  containing  RfDs  and  guidelines for short-term
effects  for  16 pesticides: alachlor,  chlordane,  l,2-dibromo-3-chloropropane  (DBCP),  2,4-
dichlorophenoxyacetic   acid   (2,4-D),   1,2-dichloropropane,  endrin,  ethylene  dibromide
(EDB), heptachlor and heptachlor epoxide, lindane, methoxychlor, oxymyl, pentachlorophenol,
toxaphene,  and  2,4,5-trichlorophenoxypropionic  acid  (2,4,5-TP).   Office  of  Drinking
Water Health Advisories will  eventually be incorporated into IRIS.
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                               EXPOSURE ASSESSMENT
     Exposure assessment  is  the  process of  characterizing  the  human populations exposed
to the  chemicals of  concern,  the  environmental  transport  and  fate  pathways  of  those
chemicals,  and  the  frequency,  magnitude,  and  duration  of the exposure  dose (U.S.  EPA
1986b).   For  exposure  assessment  of  contaminated  fish  and   shellfish,  the   following
factors should be considered:

     •     Concentrations of contaminants in aquatic biota of concern

     •     Potential  environmental  transfer  of  contaminants  from  sources  through
           aquatic species to humans

     •     Fisheries  harvest  activities,  diet, and   other  characteristics  of  exposed
           human populations

     •     Numerical  variables  (e.g.,  food consumption rate,  contaminant  absorption
           efficiency)  used in  models  to estimate exposure

     •     Purpose of  the exposure  assessment  (e.g.,  assessment  of  potential  closure
           of sport  or commercial  fishery; documentation  of health risk  from  local
           contaminant sources  such  as  hazardous waste site or wastewater discharges;
           development of sportfish consumption advisories).

Information  on  contaminant  concentrations  and the  exposed  population  is combined  to
construct  an  exposure profile,  which  includes  estimates of  average rates  of contaminant
intake  by  exposed  individuals.   Key  stages  of an exposure  assessment for contaminated
fish and shellfish are discussed in the following sections.


TISSUE CONCENTRATIONS  OF CONTAMINANTS

     Guidance  on  development  of  study  designs  to  measure  concentrations  of  toxic
substances  in  edible  tissues  of  fish   and  shellfish  is  provided  in this  section.    The
guidance  provided  below  focuses  primarily  on  field  surveys   or monitoring  programs
involving  the collection of samples directly from aquatic environments,  or  from harvesters
when the  specific geographic  origin of samples is known.  Such  guidance  is directly relevant
to analysis  of recreational  fisheries.  The present document does not specifically  address
approaches  to marketplace sampling  of commercial  fisheries  products,  although some  of
the  concepts  discussed  below  apply  to  marketplace surveys.     Sampling  designs for
collection  of  fisheries  products from the  marketplace   are available in FDA  Compliance
Program  Guidance  Manuals  (e.g.,  U.S. FDA  1986).   Sampling  of commercial  fisheries
directly at  the source is preferred  over  marketplace  sampling because  the former  often
allows documentation of the sampling location.

     If the exposure assessment is designed to include contaminant intake from consumption
of commercial fish  and  shellfish, samples may  be  obtained  in two ways.   First,  samples
of target  species can  be  obtained directly  from commercial  fishermen.   In this  case,  a

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strict  quality   assurance/quality  control  (QA/QC)  program  should  be  implemented  to
ensure  proper  handling,  storage,  and documentation  of  samples.    Documentation  should
include sampling location, species name, size  (length, carapace width,  or shell  height/width),
weight, sex, reproductive condition, time and date of  sampling,  and preservation  technique.
In  most cases,  a  technician or  observer should  be  on board  the fishing vessel to maintain
proper  sample  handling and  documentation.    Alternatively,  samples may  be collected  by
monitoring  program  personnel  using  vessels  other  than  commercial  fishing boats.    In
this  case,  samples  should  be  collected  in  a way  that  simulates  commercial  fishing
practices  as  closely  as possible  (e.g., same  species, size  classes,  season,   fishing  area,
sampling  method,  and  water  depth).   Regardless of the general  approach  to  sampling,
the  organisms  collected  should  be  placed  directly  in  temporary  storage  on  board  the
sampling  vessel.   Upon return to shore,  resection of samples  should  be  accomplished as
quickly  as   possible  using  an   adequate  clean-room.    If an  extended   sampling  cruise
necessitates   resectioning  on  board,  an  adequate  clean-space  should  be   set   aside  to
ensure that samples are not contaminated.

      Analysis  of  chemical  residues  in tissue to support  an  exposure assessment  is  one
kind  of  bioaccumulation  study.    Bioaccumulation  is  defined  here  as  the  uptake  and
retention  of a contaminant  (e.g.,  a potentially  toxic substance)  by an organism.   The term
bioconcentration refers  to  any  case  of  bioaccumulation wherein  the  concentration  of
contaminant  in tissue  exceeds  its concentration in  the surrounding medium (i.e., water
or  sediment).    The  phrase  "bioaccumulation  survey"  will  be used  below to  refer to
measurement  of chemical  residues in  tissue  samples  from fish and shellfish collected in
the field.

      The elements of  a study design for analysis of chemical residues in tissue include:

      •     Objectives

      •     Target species and size (age) class

      •     Sampling station locations

      •     Target contaminants

      •    Sampling times

      •     Kind of   sample (e.g., composite  vs.  grab,  cooked  vs.  raw;  fillet  vs.
           whole organism)

      •    Sample replication strategy

      •     Analytical  protocols, including detection limits

      •    Statistical treatment of data.

      Because the  complexity and specific features  of a  sampling design  will depend  on
the objectives  of  the  exposure assessment,  no  single design  can be  recommended  here.
Nevertheless, some basic steps in the study design process can be summarized as  follows:
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      •    Define concise objectives of the study and any hypotheses to be tested.

      •    Define   spatial   and   temporal   characteristics  of   fisheries   relative  to
           harvesting   activities   (e.g.,   seasonality,   catch  or   consumption  rates,
           species composition, size ranges, demersal vs. pelagic species).

      •    Define harvesting activities and methods of preparing food for consumption
           that potentially affect exposure to  contaminants.

      •    Define  kinds of  samples  to  be  collected  (species,  type  of  tissue,  mode
           of preparation)  and  variables to  be  measured,  based  on a preliminary
           exposure analysis.

      •    Evaluate  alternative   statistical  models  for   testing  hypotheses  about
           spatial and  temporal changes in  measured variables.   Select an appropriate
           model.

      •    When possible,  use stratified  random sampling  for  each fish  and  shellfish
           species,  where  the different strata represent  different  habitat  types or
           kinds of  harvest areas that  may influence the degree of tissue contamination.

      •    When practical, specify equal numbers of randomly allocated samples  for
           each  stratum/treatment combination  (e.g.,   habitat  type  in   combination
           with species or season).

      •    Include  samples  from  a  relatively  uncontaminated reference  or  control
           area  to help define local contamination problems.

      •    Perform  preliminary  sampling or  analyze available data  to  evaluate  the
           adequacy of  alternative   sampling  strategies  (e.g.,  composite  samples  vs.
           tissue  from  individual organisms)  and  statistical  power as a function of
           the number  of replicate samples.

      •    Develop  a QA/QC program  that covers:   sample collection  and  handling;
           chain  of  custody; data  quality  specifications;  analytical  methods  and
           detection limits;  data  coding;   data  QA/QC  steps   to  assess  precision,
           accuracy,  and   completeness;  database  management  specifications;   data
           reporting requirements; and performance audits.

      •    Define  data analysis  steps,  including statistical  tests,   data plots,  summary
           tables, and uncertainty analysis.

Note  that  the second  and  third  steps  above  depend  on information  developed  as part of
the characterization of  the  exposed population (see  Exposed  Population  Analysis below).
Also,  practical   limitations  of field  sampling  may  dictate  compromises in  the  sampling
design.   For example,  use  of equal  sample sizes  is  generally  recommended  because
statistical analysis of data  sets with  unequal sample sizes may  be difficult or unnecessarily
complex.   However, collection of equal numbers of replicate  samples for each treatment
(or stratum) may be  undesirable  if  both dominant and  rare species are  to  be sampled at
a  series of  harvest locations  with   a  broad  range of  harvest  yields.   Depending on  the
specific  objectives  and  corresponding  study  design,  a  series  of   statistical  analyses
rather than a single  test may be appropriate.

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      Detailed  guidance  on  sampling  strategies  is  provided  by  Phillips  (1980),  Green
(1979), Tetra Tech (1985b,c;  1986b),  Phillips  and Segar (1986), and Gilbert (1987).   Much
of  the guidance  provided  in  the  following  sections incorporates  the suggestions  of these
authors.

      The  statement of  objectives  is  a critical step  in  the study  design process, since
specification  of  other  design  elements depends on  the  survey  objectives.    The  study
objectives  must  in  turn relate to  the objectives  of  the  exposure  assessment  in  which
the  data  will  be  used.   The relationships  between  study objectives  and  general  features
of a sampling design are addressed in the next section.


Study Objectives and General Sampling Design

      Specific objectives  of  a chemical residue study  should be defined to ensure collection
of  appropriate  data for   the  exposure  assessment.    Different   objectives  may  require
radically  different  sampling  designs.    Although  the  primary  objective  of a field  study
may  be  to  estimate  the  mean  concentrations  of specified  chemical  contaminants  in
edible  tissues  of harvested species,  it  may  be  necessary  to  specify  additional objectives
to  meet the  needs of exposure assessment or  risk management.   For  instance, statistical
discrimination  among mean contaminant concentrations  in samples  from  different harvest
areas, seasons, or  species may  be  desired.  Such information might  be needed to manage
relative risks among harvest  areas and to  impose fisheries  closures on a site-specific basis.


Example Objectives--

      Some  examples  of  objectives  for  exposure  assessments  paired  with   appropriate
bioaccumulation  survey  objectives  are  given  below.    These  objectives  are   provided  to
illustrate  the  ways in  which the  elements  of a  bioaccumulation  study design  depend  on
the exposure  assessment  objectives.  They are not intended to be  recommended objectives
for an  actual  exposure assessment.   In  these  examples,  the bioaccumulation  study  design
involves specifically the  measurement  of chemical  residues  in  edible  tissues  of  fishery
species.   Information  on the exposed  population,  including  an analysis  of  their dietary
habits  (e.g.,  fisheries  species  consumed,  food  preparation  method,   and  consumption
rate),  is  discussed  later   (see  Exposed  Population Analysis).    Such  information  may
influence  the objectives of the exposure assessment and the bioaccumulation survey.

      Example 1:

      •    Exposure Assessment    Estimate  the  worst-case  exposure  for  a  wide
           range of contaminants over a predefined geographical area.

      •    Bioaccumulation  Design:   Estimate  mean concentrations  of contaminants
           in  edible tissues of  a  selected  narrow  size range  of  individuals  of  the
           most   contaminated  species   during  the  season  of   peak  contaminant
           concentrations.

      Example  1  represents a  screening  survey to  evaluate  the  need  for further  work.
Edible  portions  of  a  limited  number  (e.g.,  3-5)  of  individual  organisms or composite
samples would  be  analyzed for a large  number  of  compounds  and  the  risk assessment

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conducted  assuming  moderate  or  high  (but  plausible)  consumption  rates.   The  species
and  size range  selected would  be  the ones  most likely  to accumulate high  concentrations
of  contaminants.    Typically,  the  target  species  for a  screening survey  would  be  the
largest individuals of a bottom dwelling species associated with soft sediments.

     Example 2:

     •     Exposure  Assessment:   Estimate  the  long-term average  exposure to  each
           of the contaminants A,  B, and C through  consumption of aquatic species
           L, M, N,  and  O combined  from  harvest  area Z  for the average  person
           in the exposed human population.

     •     Bioaccurnulation Design:   Estimate the  mean  concentrations  of contami-
           nants A, B,  and C  in edible tissues  of aquatic species L,  M,  N, and O
           combined from harvest area Z  over an annual period.

     Example  2  illustrates a simple case involving  the  consumption  of  multiple  species
from a single   harvest location.   Individual  or  composite samples  of  each  species  would
be  analyzed  separately  during  different  seasons or  during  a  single  season  expected  to
represent   the   annual  average.    If  samples  are  analyzed   separately  during  different
seasons  (e.g., see discussion of  Example  4  below), the  mean annual exposure  for  all species
could still  be  calculated  from  the seasonal  data.   In general,  highly composited  samples
are  not recommended  because  information  on  different  factors  (e.g.,  species,  seasons)
that  affect  contaminant concentrations  is lost.

     Example 3:

     •     Exposure  Assessment:    Estimate  a  plausible-upper-limit of  exposure  to
           each of  the  contaminants A, B,  and C through  consumption  of aquatic
           species  L,  M,  N,  and  O combined  from  harvest  area Z  for a seasonal
           harvester in the exposed population.

     •     Bioaccurnulation Design:   Estimate  the  upper  bound of  the 95  percent
           confidence  interval  of  the  mean  concentration  for  each  of  the   con-
           taminants  A, B, and C  in  edible tissues of aquatic  species  L, M, N, and
           O combined from  harvest  area  Z during the season  of  highest contamina-
           tion.

     The  general sampling design for the objectives of Example 3 would  require  replicate
composite  samples to  estimate upper bounds  of 95  percent confidence  intervals for the
mean concentrations of  contaminants across species.   To  meet these  objectives,  samples
could   be  composited  across   species,   although  this   is  generally   not  recommended.
Multispecies  composites  would  not  provide  data  for  assessing  exposures  corresponding
to different  dietary  habits.  To obtain  an  upper-limit estimate of  exposure,  it  might  be
sufficient   to analyze  samples  from only  one season  if available  information  on  seasonal
variation was sufficient to  select one season  as the expected worst  case.

     Example 4:

     •     Exposure  Assessment:    Estimate  the  probability  distribution of  exposure
           to each of the contaminants A,  B,  and C through  consumption of  each
           of aquatic  species  L, M, N,  and  O from  harvest area  Z  for various

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           segments of  an exposed  population  (e.g.,  ethnic  groups) over  an  annual
           period.

      •    Bioaccumulation Design:  Estimate the  probability  distribution  of concen-
           trations  of  contaminants  A,  B,  and  C  in  edible  tissues of  each  of
           aquatic species L, M, N, and 0 from harvest area Z over an annual period.

      To  accomplish the  objectives of  Example  4,  extensive  seasonal  data  on the  dietary
 composition  of several  subgroups  of  the exposed  population  must be  available.   Separate
 replicate   composite  samples   of  each  harvested   species could   be  analyzed  for  each
 season.   During  each  season,  the species  analyzed  would  correspond to those represented
 to  a significant  extent  in the  diet.    Probability  (frequency) distributions  and  means  of
 contaminant concentrations would be  derived for  each species during each season.   By
 combining data  from  different  species, the  probability distribution  of exposure  and  the
 mean  exposure  weighted  by  species  representation  in  the diet  could be  calculated  for
 each population  segment.   Note that  data to support  the analyses  required by  Example
 4 are seldom available before a  specially designed study is  conducted.

      Example  5:

      •    Exposure Assessment:   Estimate  an   average and  a plausible-upper-limit
           of  exposure  to each  of the  contaminants A, B, and C through  consump-
           tion of each of aquatic species  L,  M, N, and O from each  of  the harvest
           areas X, Y, and Z over an annual period.

      •    Bioaccumulation  Design:     Estimate  the  mean   concentration   and   the
           upper  bound  of  the  95  percent  confidence interval  of the  mean con-
           centration  for each  of the  contaminants A, B, and C in  edible  tissues
           of  each  of species  L, M, N, and O from each of the harvest areas  X,
           Y, and Z during each  of the  harvest seasons.

      The  sampling strategy  appropriate  for  Example  5 is complicated  by  the occurrence
 of discrete harvest  areas.  Replicate  composite samples  of a given species  would generally
 be  required  for   each  season  and area  in which  the species is  harvested.   Because  the
 characteristics  of  the  exposed  population  may  differ  among  harvest  areas,  it  may be
 appropriate to divide  the exposed population into segments  corresponding  to geographic
 areas,  ethnic  groups,  age  classes  or  other  factors.    The  seasonal and  total  annual
 exposure  for  each segment  of  the  exposed population  would  be  calculated  for each
 species as in Example 4 above.


 Influence of Environmental and Population Factors—

      The  four examples just  given  illustrate the  variety of general  study  designs  that
 may  be  needed  to meet  diverse objectives.   The  specific design  of a  chemical residue
study  will depend  on  the interplay  between dietary patterns of  the  exposed  population
and  environmental  factors that  influence  concentrations  of   contaminants  in  tissues  of
aquatic organisms.  Some of the important environmental factors  are:
                                               26

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      •     Conventional water quality  (i.e., hardness, salinity,  temperature,  suspended
           solids)

      •     Habitat location, depth, proximity to contaminant sources

      •     Contaminant concentrations in water

      •     Contaminant concentrations in sediments

      •     Species available for harvest  and migratory cycles

      •     Organism activity pattern, food habits, and habitat

      •     Seasonal  biological  cycles (e.g.,  stage  of sexual cycle) in  relation  to the
           frequency and  seasonality of  contaminant inputs  (e.g., industrial discharges,
           waste dumps, dredging)

      •     Organism size (or weight), age, and  sex

      •     Lipid  content  of tissue  analyzed   (where lipophilic  organic  contaminants
           are of concern).

Examples  of  the  interaction   between  these  factors  and   parameters  of  the  exposed
population are given in Figure 3.

      Seasonal  variation in  environmental factors  or activities of the exposed  population
may correlate with  contaminant concentrations  in  consumed fish  and  shellfish.   Therefore,
at  least  general  knowledge   of   seasonal   changes in   contaminant  concentrations   and
human  consumption  patterns may  be  needed to design an appropriate  sampling approach
for estimating  long-term  exposure.   Two extreme  examples  of contamination and  diet
patterns are provided below:

      Homogeneous Diet and Contamination:

      •     Each of the species is present in the harvest area all year

      •     There is no seasonal variation in contaminant concentrations

      •     Contaminant concentrations do not vary among species

      •     Species are equally represented in the diet.

      Heterogeneous Diet and Contamination:

      •     Some species are absent  from the harvest area  during  one or more seasons

      •     Contaminant concentrations vary among species and among seasons

      •     Some  species   are  eaten more  than others, and  diet composition  varies
           seasonally.
                                               27

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                                              EXPOSED-POPULATION FACTORS •
ENVIRONMENTAL FACTORS b

CONVENTIONAL WATER QUALITY c

PROXIMfTY TO CONTAMINANT SOURCES

CONTAMINATION OF WATER/SEDIMENTS

SPECIES AVAILABLE FOR HARVEST

ORGANISM ACTIVITY MODE d

SEASONAL BIOLOGICAL CYCLES •

ORGANISM SIZE

ORGANISM AGE

ORGANISM SEX

LIPID CONTENT OF TISSUE
-O
-O
-O
             8 Harvest activities and dietary patterns of exposed population:
               Mode of harvest refers to fishing technique (e.g., trap.net, or pole)
               Mode of preparation refers to trimming and cooking technique
             0 Factors that influence contaminant concentrations in aquatic organisms
             c Hardness, salinity, temperature, suspended solids
             d Degree of mobility and contact with sediments
             6 Reproductive, lipid storage, and growth cycles


             •4    Population factor affects environmental factor

             O    Environmental factor affects population factor

             V    Mutual interaction between environmental and population factors
       Figure 3    Interaction between environmental factors and exposed
                   population factors.

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In  the first  case  above  (homogeneous  diet  and  contamination),  the study  design  could
be  relatively  simple.   Mean  contaminant concentrations  could be  estimated  from  analyses
of  a  single  composite sample of one  of the  species collected  at  one  time  of  year  from
each  harvest  area.    If previous  data  were  available  to verify the  lack  of  variation  in
chemical  concentrations  among species  and  among  seasons,  it  would be  appropriate  to
extrapolate  the results  from  a single  composite  sample  to the entire diet  composed  of
several species.     However,  this  is  an  unrealistic  case.    It  is  more  likely  that   both
contaminant  concentration  and diet  composition will  vary seasonally,  and that contaminant
concentrations  will  vary  among  species.    Analyses  of  contaminant  concentrations  in
each  species  during  different  seasons is generally recommended here  to  meet the  diverse
objectives of a typical exposure assessment.


Selection of Target Species and Size Classes

      Ideally,   the  set of  species  selected  for  contaminant  analysis  would  include  all
harvested species.   Because  available  data  and  funds  for  collecting  new  data are  often
limited,  only  one or  a  few  target species  may be used  for human  health risk  assessment.
The  particular species  selected  for  an  exposure assessment  will  depend  on  the  study
objectives.   Examples of  approaches  and   guidance on selection  of target  species  are
given below.

      Four alternative  objectives that affect the choice of target species  are:

      •    Perform a  comprehensive  analysis of  harvested species

      •    Characterize  the   typical  exposure  case  represented  by  the   dominant
           harvested species

      •    Characterize  exposure  for the worst-case  species  (e.g.,  heavily  consumed
           species expected to be highly contaminated)

      •    Characterize  the  spatial  distribution of contamination  using an  indicator
           species.

The criteria  for selecting  species  for  chemical analyses to meet each of these objectives
are shown  in Table  4.    For the  first  objective (comprehensive  species  analysis),  all  of
the  harvested  species do  not necessarily  need   to  be  analyzed,   but  some criterion   is
required  to  select species  for analysis  (e.g.,  the most important  species  in  the  harvest
that together  comprise greater than  95  percent of the  catch  by weight).   For  the second
objective (typical  exposure),  a few of  the  dominant species (by  weight)  in  the  harvest
may  be selected  to   represent a  typical  exposure  level.   However,  this  approach  has the
major disadvantage  that  highly  contaminated species may  be  overlooked  (see  Dominant
Harvested  Species  below).    For  the  third  objective  (worst-case  species   analysis),  the
target species should be  among  the  most  contaminated species in  the  harvest.   If the
worst-case  assessment is  species-specific (i.e.,  the consumption rate  for  a  single species
is  used to estimate exposure), then  the  target species should  also  be one of the dominant
species in  the harvest.  When the dominant component of the diet differs among subpopu-
lations  of concern,  then  specific dietary  information  for  subpopulations should  be used
to select  the  worst-case  target species.   The target  species  may be  the most  contaminated
species regardless  of its  status  in  the  diet  of  the  entire exposed  population.    For the
last  objective  (site-specific  analyses  of  the  spatial distribution   of contamination),  an

                                               28

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                           TABLE  4.   CRITERIA FOR  SELECTING  TARGET SPECIES'
   Species Characteristics
Comprehensive
Species Analysis
Alternative Design Objectives'3
    Typical            Worst-Case
 Exposure Case           Species
 Spatial Pattern
Indicator Specie
Harvest ranking
Home range size
Contamination level
Species forming
>95°/o of catch
Variable
Variable
Dominant species
in catch
Variable
Variable
Dominant species
in catch
Variable
High
Variable
Small
High

* Criteria for selecting target species to meet a given objective are shown in bold.

b A full statement of each objective is given in the text.

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indicator  species  with a  small  home range  that  is  expected to  have high  concentrations
of  contaminants  in  edible  tissue  would  be  selected.    Note  that  an  indicator  species
could  be  a species  that is relatively  rare  in the  harvest.   Although  home  range  size
and  degree  of contamination  of  species  may not  constrain the selection  of  species  to
meet  the  first  two objectives listed  above,  selecting species without regard to contamination
levels  will  not  necessarily  ensure  that  the overall  purpose of  performing  an  exposure
assessment will be met.
Dominant Harvested Species--

     If  available,  data  on  fisheries  catches  or  consumption  from  field  surveys  (e.g.,
Finch  1973;  Puffer et al.   1982;  Landolt et  al. 1987; McCallum  1985)  can  be  used  to
select  species  for  analysis   that are  dominant  members  of  the  catch  on  a  wet-weight
basis.  The advantages of choosing  the  dominant harvested species for exposure assessment
are that:

     •    Exposure estimates   will  be  based  on  realistic  conditions  in  terms  of
           relative  contribution  of  species  to  the  diet,  providing  that  catch  data
           reflect consumption  patterns or  that  consumption  data  are  used  for  the
           selection of species

     •    Adequate numbers of organisms for chemical analyses  should  be relatively
           easy to obtain.

The disadvantages of this approach are that:

     •    Species that  are  minor  components  of  the  diet  by weight but that are
           highly contaminated may be overlooked

     •    Exposure of human  subpopulations that  consume  species other than the
           dominant component of the diet overall may not be protected

     •    Which species  are dominant often  varies spatially,  making it  difficult  to
           compare risk estimates for different sites

     •    Extensive species-specific data on catch, consumption, and  contamination
           patterns  are  needed  to  select target species  (these  data are  costly  to
           obtain if not already available)

     •    If samples  are  obtained directly  from harvesters,  a major component of
           the catch may  be  unidentifiable  because  the  catch  is sometimes  cleaned
           before being surveyed.


Indicator Species—

     The  use  of  selected   indicator species  is  an  alternative   to  the   use  of  dominant
harvested species.   Indicator species  can be chosen  to represent the  average (or maximum)
contamination  levels in  the harvest,  as  determined from available  data  or  from  a  pilot
survey.   Use of indicator  species  may be  appropriate for  investigations with multiple
objectives   (e.g.,  assessment  of  bioaccumulation  in   fishery  species and human  health

                                               29

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risks  for  specific  areas  within  a  water  body).    Indicator  species  may include  both
highly  mobile  and  relatively  sedentary species.    If  small-scale  discrimination  of spatial
patterns of contamination  is a concern, indicator  species should  include  nonmigratory biota
or  species  that  exhibit  minimal  movement  within  the  aquatic   habitat  (e.g.,   bivalve
molluscs and English sole in nearshore marine areas; mussels and sculpins in streams).

      The  use  of  a  few  indicator  species for  exposure  assessment  is  appropriate   for
initial  screening  of  geographic  areas  before   more  detailed  exposure  assessments   are
conducted.   If no   potential  health  problems  are  identified in  an  initial risk  analysis,
further  data  collection  may  not  be  warranted,   unless long-term  monitoring  is  desired.
If,  on  the  other  hand,  analysis  of  tissues  from  indicator  species  reveals   substantial
health risks, further  field surveys  may  be  needed to perform  a  detailed exposure assess-
ment, using  consumption  patterns  and  contaminant  concentrations  for  a  wider  variety
of harvested species.

      The use of indicator species for exposure assessment offers the  following advantages:

      •    Field  surveys  based   on  indicator   species  are  cost-effective  because
           efforts can be  focused  on collecting  large sample sizes of one  or  a few
           species rather than minimally adequate sample sizes of many  species

      •    Background  information  on  the  distribution,  abundance,  and contamina-
           tion  of indicator species may be  available

      •    Indicator species  can  be  selected to  represent  the average  or  maximum
           level  of  contamination  expected  for   all  harvested   species   (assuming
           background or pilot  data are available)

      •    Because  the indicator  species does  not  have  to be a dominant  species  in
           the  harvest, extensive  data  on  catch  and  consumption patterns  may not
           be needed.

The disadvantages of the indicator species approach are that:

      •    The  exposure  estimate  may  be  biased  if  the  indicator  species does not
           truly represent  the  case  of  interest  (e.g., average- or  worst-case concen-
           trations of contaminants)

      •    The  selected  species  may be a  good  indicator  for  some  contaminants  of
           concern but not for  others

      •    If  the   selected  indicator  species  are  not  major  components  of  the
           harvest, the exposure assessment  may appear unrealistic

      •    Background  data on  the distribution,  abundance, and  contamination  of
           the  harvested  species  are usually  needed  to select  appropriate  indicator
           species.

      Phillips  (1980),  Tetra  Tech  (1985b), and Phillips and  Segar (1986)  provide  criteria
for selecting  target species  for  bioaccumulation   surveys.    Important  criteria  to  consider
when  choosing  indicator  species  for  an  exposure  assessment   are  listed  below.    The
target species should be:

                                               30

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     •     Harvested by  the  exposed population or be  representative  of the contami-
           nation levels in the primary harvested species

     •     Relatively sedentary to be representative of a specific study area

     •     Easy to sample and abundant enough to obtain adequate samples

     •     Large enough  to yield an adequate sample size for chemical analysis.

Some  additional  criteria for  target  species  to  be  used  as  indicators  of contaminant
concentrations in the environment are:

     •     Contaminant  concentrations  in  the target  organisms  should  be  related  to
           those  in the environment

     •     Metabolic  regulation  of  contaminant concentrations by  the  target species
           should be absent or weak

     •     Contaminant   interactions  should  not  greatly  diminish  the  usefulness  of
           the  target  species as a  site-specific indicator  when  contaminant compo-
           sition is expected to differ among sites

     •     Target  species should  integrate  the  effects  of  contaminant  uptake  over
           time.

     A summary of indicator species recommended by Tetra  Tech (1985b) for  monitoring
of  chemical residues  in  marine and estuarine  species is  shown  in  Figure  4.   Many of
the  recommended  indicator species are associated  with soft-sediment  substrates.   Contact
with sediments  by  such  species may lead to  body burdens of contaminants  that are  high
relative to  those in  pelagic organisms  of similar lipid  content and size.   However, the
relationship  of  contaminant  concentrations   in   demersal  (bottom-dwelling)  vs.  pelagic
(open-water)  organisms  is  difficult to  predict  without  extensive  data.   As  shown  by
Tetra Tech (1986c), English sole  may  be used  as  an indicator of the order-of-magnitude
contaminant concentrations   that  would  be  expected  in  edible  tissues  of  pelagic   fish
species  in  Puget Sound,  WA.   However, relative  contamination among  species  may  vary
among  bays within Puget Sound.   For example, in Commencement Bay,  the average  PCB
concentration  in  muscle  of English  sole was about  twice that in  recreationally harvested
pelagic  species  (Pacific   cod, Pacific hake, Pacific tomcod, rockfish, walleye  pollock,  and
white-spotted greenling;   based  on  data  from Gahler  et  al.   1982).    In  Elliott Bay, the
average PCB concentration  in  angler-caught English  sole was  about  0.4 times  that in
harvested   pelagic  species (sablefish, squid,  Pacific  cod,  Pacific hake,  Pacific  tomcod,
rock sole, and  rockfish;  based  on data from Landolt  et  al.  1985).  Site-specific data are
needed  to  evaluate contamination  of potential  indicator  species relative  to  contamination
in other species of interest.

     Apparently, no  comprehensive  review  of target  species for  bioaccumulation  studies
in  lakes  and streams has been conducted.    However, it is  clear that  salmon  and  trout
(Salmonidae),  perch  (Percidae),  and  sunfish  (Centrarchidae)  species  will  be  preferred for
tissue  analysis in  many  cases   because  they constitute the bulk of  the  fisheries  harvest.
Freshwater  mussels,  especially  Anadonta  spp.  and  Corbicula  spp.,  crayfish,  sculpins


                                               31

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                    FISHES
                          ~7
                                      INVERTEBRATES
LOCATION
         t/////////////////
MASSACHUSETTS/
RHODE ISLAND
NEW JERSEY/
VIRGINIA




FLDRIOMJSW _.







































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1 • 1























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PUERTO RICOMAIMWI
Note: See Appendix Table D-1 for scientific names of recommended target species.
Reference: Tetra Tech (1985b)
"7
   Figure 4 Summary of recommended marine and estuarine indicator species.

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(Cottidae),  and catfishes  (Ictaluridae) may  be preferred  as  target  species  for  site-speci-
fic analyses.


Size  Classes--

     A  study  design  for  analysis   of  chemical   residues  should  incorporate   stratified
random  sampling  of  a  selected  size  class  or  various  size  classes  within  each   target
species.    Stratification  by  size  is  extremely  important, since  both  lipid  content  and
contaminant concentrations  can  vary  greatly among   different  sized  organisms  of  the
same species (Phillips  1980).   Moreover,  the  nature   of the  relationship  between  body
size  and  contaminant  concentration  varies among  chemicals,  among species,  and possibly
among sampling stations and seasons  (Phillips 1980; Strong  and Luoma 1981; Sloan  et  al.
1985; Johnson  1987).   The size  classes  of each  species selected  for  analysis  should  be
representative  of  those  in  the diet   of the potentially  exposed  human population.    For
persistent  chlorinated  organic compounds  and  organic  mercury  complexes,  the  largest
(i.e., oldest) individuals within  an  aquatic  species  are expected to be the most contaminated.
If organic compounds  are of concern and a limited analysis  is planned, the  study  should
focus on the largest individuals likely to be harvested by the exposed human population.


Sampling Station Locations

     Two  general approaches  to  field  sampling  are possible.   First,  the  investigator  can
obtain  samples directly  from  harvesters.   This  approach   has  the  advantage  that   the
sampled  population  is  the population of  direct  interest  for  the exposure and risk  assess-
ments.   However, one drawback  of  this approach is   the  potential for contamination or
degradation  of samples  due  to  handling of the  samples by  the  harvesters.    Moreover,
the  precise  sampling  locations may  be  unknown  if   samples  are  collected at  dockside
from recreational or  commercial fishing  boats.    The second   approach  is   to   obtain
samples  independent of  the normal  harvesting efforts,  allowing standard sample handling
practices  to  be  implemented.    Independent sampling  also  facilitates  the  collection  of
adequate  samples  for stratification  by  organism  size,  habitat,  or some  other  variable.
The  remainder  of this section addresses  a  sampling effort  that is  independent of  normal
harvesting activities.

     Sampling  stations should generally  be located in  known harvest  areas.   However,
additional  stations  in  relatively  uncontaminated  reference   or  control areas should  also
be sampled.   By comparing results  among  harvest areas and  between  each harvest  area
and  the  reference station, one  can establish  not  only   the degree of spatial  heterogeneity
but  also  the magnitude of  elevation above reference  of contaminant  concentrations (and
corresponding  health   risks)  at each  harvest area.   Because  sampling  depth  or vertical
position  on the  shore  may influence   contaminant concentration  in  aquatic  organisms,
reference station characteristics should be closely matched  to those for the harvest areas.

     Sampling  stations may be located  within  a  study area according  to  one  of  several
probability  sampling  designs (Figure  5).   Gilbert (1987) provides  a  concise summary of
conditions under which each sampling  design  is preferred.

     Simple random  sampling implies that  each individual  organism  within a species  has
an equal  chance  of being  selected for  measurement and that  selection of one  individual
does  not influence selection of  others.   A simple random sampling strategy  is  appro-

                                               32

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             SIMPLE  RANDOM
                SAMPLING
              •  '•   .'•
STRATIFIED  RANDOM
    SAMPLING
                                                          — STRATA
PRIMARY —
  UNITS
               TWO-STAGE
                SAMPLING
     CLUSTER
     SAMPLING
                     — CLUSTERS
            SYSTEMATIC  GRID
               SAMPLING
e
e
•
e
•
e
e
e
e
e
e
•
 RANDOM  SAMPLING
  WITHIN  BLOCKS
                                      Reference: Gilbert (1987)
     Figure 5   General sampling station layouts for probability sampling in
               two dimensions.

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priate  if there  are  no  major  trends  or  patterns of  contamination  in  the  study  area.
Note  that sampling  of fish  or shellfish with sampling  gear  (e.g., hook and  line,  nets) will
always be nonrandom to some extent because of the selective nature of the gear.

     Stratified  random  sampling involves  random  sampling  within  nonoverlapping  strata
of a  population  (e.g.,  subareas based on  concentrations of  fishing effort).   This  sampling
approach  is  appropriate when geographic  areas within  a  harvest  region  are heterogeneous
relative to the kind or degree of contamination.

     Two-stage  sampling  involves   random  or  systematic  subsampling  of  primary  units
selected  by  a random sampling  technique.  For example,  fish  could  be collected randomly
from  a given  stream reach.   In the second stage  of  sampling,  subsamples  of fillet from
each  fish could be  selected randomly  for chemical analyses.   Multistage  sampling  is  an
extension of two-stage sampling.

     Cluster sampling  involves  choosing  groups of  individual organisms  at random, then
measuring  contaminant  concentrations  in  all   individuals   within  each  cluster.   Cluster
sampling is  sometimes  used  to estimate  means  if clusters of sampling  units (e.g.,  individual
organisms in  a clump) can be selected randomly more easily than  can individual units.

     Systematic  sampling  consists of  sampling at  locations and/or  times  according  to a
pattern.   For  example, samples  may be  collected at equidistant  points  on  a  spatial grid
or  at  equally  spaced time intervals.    Systematic sampling is  generally  preferred   for
mapping patterns of contamination.   As  such, it  is  more appropriate  for soil  or sediment
sampling  than  for bioaccumulation  studies.    The  random-sampling-within-blocks  strategy
shown in Figure 5 combines systematic  and random sampling.   Such procedures  produce
more uniform coverage than does simple  random sampling.
                                                                              i

     Gilbert (1987)  describes systematic  sampling  approaches for  locating  "hot spots"  or
highly contaminated local areas.  He addresses the following questions:

     •   "What grid spacing is needed to  hit a  hot spot with specified confidence?"

     •   "For a given grid spacing,  what is the probability of hitting a hot spot
          of specified size?"

     •   "What  is  the probability  that  a hot spot  exists when  no  hot spots were
          found by sampling on a grid?"

If grid  sampling is  to be  applied  to a bioaccumulation  study,  the  target species must
exhibit limited  mobility.    Grid sampling can  also  be  applied  to  collection of aquatic
sediment samples. Gilbert (1987) provides  guidance on spacing of grid samples.

     Grid sampling  is especially  appropriate  for  identifying  environmental contamination
associated with  discrete sources  of pollution  such as  industrial  discharges, storm  drains,
and  combined  sewer  overflows.   The  use of caged  mussels is  a promising approach  for
identifying  sources  through  chemical  residue analysis.    As part  of  the  Long  Island
Sound  Estuary  Program,  EPA  Region  I  is  using  caged  mussels  to  monitor  chemical
contaminants entering  the Sound from tributaries.   The  California  mussel  watch program
(e.g.,  Ladd  et  al.  1984),  the U.S  mussel  watch (Goldberg et al.  1978, 1983; Farrington et
al.  1983), and  the  NOAA  status  and  trends  program  (Boehm 1984)  illustrate the  use  of
both  resident and caged  transplant  mussels  to  monitor bioaccumulation of  toxic chemicals

                                              33

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over  space and time.  Toxic chemical residues  in  mussels are  excellent indicators of point
source  discharges  as  well  as  pollution  gradients (Phillips  1976;  Popham  et  al.  1980;
Phelps  et  al. 1981).   U.S.  EPA (1982) described  recommended protocols for  caged mussel
studies.

      A  combination  of  two-stage  and stratified-  random (or  stratified-grid) sampling  is
recommended  here  for  most  studies of   fisheries  contamination  to  support  exposure
assessment.   The  two  stages  correspond  to  an  individual  organism  and  edible tissue.
Samples of  individual organisms  may or may not be composited  depending on  specific
study  objectives (see  below,  Kinds  of  Samples,  Composite  Sampling).   Sampling  strata
may  include harvest area, species,  and  size classes.    Other  sampling strategies  may  be
either too simple  or inappropriate  to meet the typical  objectives of  exposure assessment
studies.
Time of Sampling

      The  timing  of bioaccumulation surveys should  be based on  the temporal distribution
of  harvest  seasons  and  inherent  biological  cycles  of  target  species.    The  timing  of
harvest periods depends  on the availability of fishery  resources, which  may be influenced
by  the  migratory patterns  and  feeding cycles of  target  species.   Biological cycles  that
influence  an  organism's  susceptibility  to  bioaccumulation  should  also  be  considered
when  choosing  a sampling  period.   The most  important  of  these  is  the reproductive
cycle, which  is  discussed  further  below.   In  crustaceans  (e.g., crab  and  shrimp), the
molting  cycle  also  determines  the  potential for bioaccumulation of  toxic chemicals.   The
rate  of uptake   of contaminants   by  crustaceans  is  highest  just   after molting,  before
hardening of the integument limits its permeability.

      The  reproductive  cycles  of  aquatic  organisms  may  exert  a  major influence on
tissue   concentrations  of  many  contaminants,  especially  organic   compounds  (Phillips
1980).   If a  worst-case analysis is  desired,  the  target species  should  be sampled  at  a
time  during the  harvest period  when  tissue  contaminant  concentrations  are expected  to
be  at their  highest  levels.   An  effort should  be  made to  sample  at or  just  before the
peak  of reproductive  ripeness, before  gametes or offspring  are  released.   At  this  stage
of  the  reproductive  cycle  for  a   given  species,   lipid  content and  concentrations  of
organic  contaminants in tissues  should be at  their  highest  levels.    Because the time  of
sampling  should  be  tailored  to the  reproductive   characteristics of the  target  species,
sampling periods  may  vary among  species.  However, once a  sampling  period is chosen,
it should remain constant over time if an ongoing monitoring  program is planned.

      An  alternative  approach is  to   sample  throughout   the  harvest  season  for  each
target species.    In  this  way,  representative values  can  be obtained  for estimating means
within  sampling periods and  for detecting seasonal  or long-term trends.   In most  cases,
exposure  assessments will  be  performed  over relatively  short periods  of time (e.g.,  a
year), and  multiyear sampling  may not be required.   Within  a  harvest -season,  however,
sufficient samples should be collected  to estimate the mean concentrations of contaminants
during  the  harvest period.     To  estimate temporal  variation  or  to  obtain  worst-case
estimates,  replicate   samples  will  be  needed  at several  times  within the  harvest  season.
The frequency of  sampling  should  be related to  the expected rate of  change  in  tissue
concentrations   of  contaminants.     For  an  extensive   review  of   temporal  changes  in
bioaccumulation  and body  burdens  of  contaminants  in  aquatic  organisms, the  reader
should consult  Phillips (1980).

                                               34

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Kinds of Samples

      The  kind of  tissue sampled and  the  sampling unit  (i.e., individual organisms  vs.
composites  of several  organisms) greatly  influence  the  sensitivity,  precision,  and  repre-
sentativeness  of  an  exposure  assessment.   The  issues  of composite  sampling  and sample
preparation techniques are addressed in the following sections.


Composite Sampling--

      An  alternative  to  the  analysis  of  tissue from individual organisms  is  the analysis
of  composite  samples.    Composite  tissue  sampling  consists  of  mixing  tissue  samples,
each  called  a subsample,  from  two or  more individual organisms  typically  of  a  single
species collected at  a  particular site and  time period.   The  mixture is then  analyzed  as
a single sample.   The  analysis of a composite sample  therefore  provides  an  estimate  of
an  average tissue concentration for the  individual organisms that make up the composite
sample.   Composite  sampling  is  a  cost-effective  strategy  when  the individual  chemical
analyses are  expensive  but the  cost  of collecting  individual  samples  is   relatively  small.
The collection  of  composite  samples is  required in  cases  where  the  tissue  mass  of  an
individual organism is insufficient for  the analytical protocol.

      Bioaccumulation  surveys   designed  to   support  exposure  assessments  may  use   a
composite  sampling  strategy.    Current  risk   assessment  models  used by   EPA are  based
on  estimates  of long-term  average  exposure.   Estimates of  the mean concentrations  of
contaminants  in edible  tissue  samples  from harvested  organisms  are  used  as  estimates
of  the exposure  concentrations for  human  consumers of fish  and  shellfish.   Composite
sampling  of the tissue  from selected organisms is a method  for  preparing a  sample that
will  represent  an  average  concentration.    The  collection  of  replicate composite   tissue
samples  at  specified  sampling  locations  will  result  in  a more  efficient   estimate of  the
mean  (i.e.,  the  variance  of  the  mean  obtained  with  replicate  composite  samples  is
smaller than that obtained with the collection of replicate samples of individual organisms).

      One  major disadvantage  of composite  sampling  is  the inability to directly estimate
the  range  and  the  variance  of the underlying  population  of  individual  samples.   Such
information is extremely useful in bioaccumulation monitoring programs as an early warning
signal   of   increasing levels  of  contamination.    For  example, only  a   few   individuals
within  a  sample may  contain  high contaminant  concentrations.   Mixing these  individuals
with  less  contaminated  organisms  in  a composite sample  at  a  given  station may dilute  the
contaminants  and  mask  a potential  problem.   In exposure  assessment, the patchy distribution
of  highly  contaminated  fish or  shellfish  may indicate  the  spatial  distribution  of sources
of  contaminants.   Also,  a  lack of data  on individual samples  may  mask the potential  for
short-term   health   effects  (e.g.,  learning   disabilities,  neurological   malfunctions)   in
sensitive individuals  or  in  those  who consume excessive amounts  of highly contaminated
organisms  over a  short period of  time.   In  some  cases,  however,  preliminary  exposure
and  risk  assessment calculations  could be  performed   to  justify  focusing  on  chronic
effects (e.g., carcinogenesis).

      The  benefits  of  compositing  individual  samples  from  a  single station   within  a
given  sampling period  often  outweigh  the disadvantages just discussed.   In  such  cases,
Rohde  (1976) and Tetra Tech  (1986b)  provide a method for calculating  the  variance  of

                                               35

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the  underlying  population  of  individual samples  when the  variance of  the  composite
samples is known:

                           Var X - n (Var Z)                                          (3)

where:

        Var X «=  variance of the mean of individual samples
        Var Z »  variance of the mean of composite samples
            n -  number of subsamples constituting the composite sample.

This  equation  assumes  that  replicate  observations from  individual  and composite  samples
are  normally  distributed.    Also,  the  composites  must each  consist of  subsamples  of
equal  mass (i.e., the same mass of tissue  is  taken  from  each  organism).   For  unequal
proportions  of  composite  subsamples  (i.e.,  tissue  mass),  the  variance  of  the  series  of
composite samples  increases and, in  extreme cases, exceeds  the  variance  of grab  samples.
Thus,  it is  recommended here that the same mass  of tissue be taken from  each organism
contributing  to  a  composite  sample  of  a single  species.   For  the analyses  presented
below, it was assumed that the composite samples consist of subsamples of equal proportions.

      Two  special  cases  of   composite  sampling  are "space-bulking" and   "time-bulking"
(cf.  Phillips  and Segar  19S6).   Space-bulking  involves  sampling of  individual  organisms
from several  locations and combining  tissue  samples  into  one or more composite samples
for  analysis.   Time-bulking  involves  taking  multiple samples over   time  from  a  single
location and compositing  these samples.  Time-bulking over a  harvest season  is especially
appropriate  where  short-term  variations in contaminant concentrations  in   tissue  samples
are significant and budget constraints preclude repeated  analyses over time.

      The  adoption  of  space-bulking  or time-bulking strategies  ultimately   relates  to  the
objectives  of  the  exposure   assessment.    Because exposure concentrations are  typically
averaged over  time  in  risk  assessment  models,  time-bulking may  be more justified than
space-bulking.    In  any  case, one  should use these strategies with extreme caution since
significant  information  on spatial  and  temporal  heterogeneity  may  be lost.   Selection  of
space-bulking or time-bulking  techniques  should be  supported  by  analyses of  available
data  or data  from  preliminary sampling.   Tiered  analyses  of  samples can also be used
to  evaluate  the  appropriateness  of   compositing  strategies.    For   example,  individual
samples may  be  stored  separately  over  the  entire harvest  season.   At  the  end  of sample
collection,  preliminary  analyses  of individual  tissue  samples from  a selected  series of
sites  and  times  could  be  performed  to evaluate temporal  and spatial  heterogeneity and
to devise an appropriate  compositing strategy.

      Tetra  Tech (1986b)  evaluated the  effects  of  composite sampling  on the statistical
power of  a  sampling  design (see  Appendix  D).    Their  results  demonstrate  that  the
confidence in  the  estimate of the mean  concentration of contaminant in  tissue  increases
as the  number  of  individual samples  in the composite  increases.    The statistical  power
(i.e.,  the   probability  of  detecting a  specified  minimum  difference  among  treatments)
increases dramatically with the  number of individual samples in each replicate  composite
sample.   However,  the benefit of  adding  more  individual samples to  each  composite
eventually  decreases  with  each successive  increase in  the  number of individual  samples
per composite.  For moderate levels of variability in chemical residue  data, 6-10  individual
samples within  each of  5  replicate  composite  samples  may  be  adequate  to  detect  a
treatment   difference  equal   to  100   percent  of  the  overall   mean  among  treatments.

                                              36

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Rohde  (1976),  Schaeffer  et  al.  (1980),  Brumelle et  al. (1984), and Gilbert  (1987)  also
discuss statistical aspects of composite sampling.


Sample Preparation--

     Tissue  samples should be  removed from  target  organisms and  prepared  for  analysis
according  to a  well-defined  protocol.    Tissue  preparation  methods  can  greatly affect
the results  of bioaccumulation analyses  (Smith  et al. 1973; Skea  et  al.  1981;  Puffer  and
Gossett   1983;  Landolt  et al.  1987).    In  specifying  a  tissue preparation  protocol,  the
following issues  should be addressed:

     •     Type of tissue (e.g., muscle fillet, whole body, internal organs)

     •     Location of tissue in organisms' body

     •     Removal of any or all of shells, scales, skin, and subcutaneous fat

     •     Raw  vs. cooked samples and cooking method

     •     Homogenization method

     •     Minimum sample mass for each kind of analysis.

The  kind  and  location  of tissue analyzed  may influence the  realism  of  the exposure
assessment.   For  example, most  humans consume only  fillets  of fish,  not internal organs
or whole fish.   Because  internal organs are often  more  contaminated by  toxic chemicals
than are  fillets, exposure  estimates based  on  chemical  analyses of  organs  or  whole  fish
could  be  unrealistically  high.    Removal   of   skin  and  subcutaneous  fat   from  samples
before  chemical   analysis  generally  reduces   the   mean   concentrations  of   chlorinated
organic  compounds.   However,  this practice may  also reduce the  variance  of measure-
ments,  allowing  more   sensitive  discrimination  among  statistical treatments  (e.g.,  species
or sampling  locations).   Even   within  the  fillet tissue,  contaminant  concentrations  may
vary depending  on the original  location of the sample on the fish's  body.   Cooking of
fillets before chemical  analysis  may result  in  a 2-64 percent decrease in the concentra-
tion  of PCBs relative  to the uncooked sample, but the  results  vary greatly with species
and  cooking  method (Smith  et  al.  1973; Skea  et al.  1981).   However, cooking may  also
activate  or  transform  chemicals  to  create  carcinogens  (e.g.,  creation  of  benzo(a)pyrene
during  char-broiling).     Finally, adequate   homogenization of samples  before  they  are
analyzed is necessary to obtain  representative results.

     Because information on  the effects  of tissue  preparation  methods on  the  results of
chemical  residue analyses is  limited, it  is  recommended that  a pilot survey  be performed
to  establish  consistent,  reliable  methods.    Relevant  protocols for  sample  storage  and
preparation  are  available in  a  bioaccumulation  monitoring guidance document  issued  by
the EPA  301(h) program  (Tetra  Tech  1986e)  and  in the EPA Interim Methods  for  the
Sampling  and Analysis  of  Priority  Pollutants  in Sediments  and  Fish  Tissue  (U.S.  EPA
1981).   Because  many  decisions  about sample preparation depend on the specific  objectives
of  the   study,  no  single protocol  for sample  preparation  covers  all  of  the  possible
approaches.   For  example,   samples  are  usually  blotted  dry before  being  weighed  to
obtain  an  estimate  of wet  weight.   However,  when  bivalve  molluscs  are being prepared
for analysis, it may be desirable to retain  excess water for  later analysis.

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       Analysis  of  raw edible tissues  is recommended to provide  data on  the concentra-
tions of contaminants  initially present in tissues that are normally consumed.   Eventually,
it  may  be  possible  to   mathematically account  for  cooking  effects  in  the  exposure
assessment. At present, however,  data on cooking effects are highly variable.


Sample Replication

      Replicated   measurements  of  contaminant   concentrations  in   tissue   samples  are
needed to  perform uncertainty analysis  (e.g., characterizing the  precision of  the  estimates
of  mean contaminant concentrations).   Replicated  data are also needed for many statistical
tests  of spatial  and  temporal trends.   Sample  replication  is recommended  here  for  all
bioaccumulation  measurements to be used in  exposure assessments.  Guidance  on  selection
of  a sample  replication scheme  is provided  in  Appendix £.   In most cases, at least five
replicate samples  of individual fish (or shellfish) are required  to  provide  minimal statistical
power (e.g.,  ability to discriminate  a  treatment  difference equal  to  200  percent  of  the
overall  mean among  treatments).     Increases  in  sample  replication  beyond  about  10
individual   replicates  clearly  do  not   provide sufficient  benefits  in   statistical  power  to
justify  added costs of  sampling  and  analysis  (Appendix  E).    Greater  power  can  be
achieved in a cost-effective manner by composite  sampling if  information  on contamination
of individual  organisms is not needed (Appendix D).


Selection of Analytical Detection Limits and Protocols

      Criteria  for  selection of method  detection  limits  for  analytical protocols  may  be
based  on   risk  assessment  models  explained  below  (see   Risk  Characterization).   For
example, the  analytical chemistry  methods may be chosen  to enable detection of a chemical
concentration  associated  with  a   specified minimum  risk level  defined  as  acceptable  by
risk  managers.     Other  factors   may  dictate choice  of a  lower  detection  limit.   For
example,  routine  analytical methods may attain  much  lower  limits  than required  by the
specified  minimum detectable  risk  level.  Also,  lower detection limits may be desired  if
an  objective  of the study  is  to  develop baseline bioaccumulation data  as  well as  health
risk data.   In  some  cases (e.g.,  2,3,7,8-tetrachlorodibenzo-p-dioxin,  benzidine,  dieldrin,
N-nitrosodimethylamine), the  minimum detection  limit that can  be achieved  with  current
technologies  corresponds to  a plausible-upper-limit risk that is  substantially  above risk
levels  of  potential concern  (e.g.,  10"6  to   10"6).   Tetra Tech (1985c)  provides  further
guidance on detection limits for bioaccumulation surveys.

      Approved  routine  EPA  methods for  sampling and full-scan  analysis   of  chemical
contaminants  in tissues  are  not  available.    U.S.  EPA (1981)  published  interim  methods
for sampling  and  analysis of priority pollutants  in  tissues.   EPA-approved protocols  for
chemical  analysis  of  water  samples   were  adapted  for  application  to  tissue  samples  as
part  of  the  Section  301(h)  marine  discharge waiver program of the Office of  Marine
and Estuarine Protection [see  Tetra Tech  1986e for  301(h) sampling and analysis protocols}.
Specifically,  301(h)  analytical methods  for  extractable organic  compounds  were  adapted
from Method 1625 Revision  B (U.S.   EPA  1984a) and  additional guidance  from  the EPA
Contract Laboratory Program  for  Organic Analysis (U.S. EPA  1984c).  When applicable,
the  301(h) protocols  incorporate  established   EPA  advisory  limits  for  precision, accuracy,
and method performance (U.S. EPA 1984c).   The  EPA Office  of Acid Deposition,  Environ-
                                               38

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mental  Monitoring, and  Quality Assurance  is  developing  further  guidance on  sampling
and analysis methods to support exposure assessments.

     Other available  methods  for analysis  of  chemical  contaminants  in  tissue samples
include those  used by  U.S.  FDA (1978),  NOAA (MacLeod et  al. 1984), and Ozretich and
Schroeder  (1985).   These  analytical  protocols  are  designed to  apply  to  specific subsets
of the  EPA  priority pollutants.   U.S. FDA  (1978) methods, as  described  in the  Pesticide
Analysis Manual, include variations in procedures for tissues differing in lipid content.

     The  choice  of  an  analytical   protocol  may  be  influenced  by  available   financial
resources.   Chemical analysis  of samples is often the  most costly  portion of a  sampling
and  analysis  program.    Higher  analytical costs  may  be required  to  achieve  greater
sensitivity  (i.e.,  lower  detection  limits).    Examples  of  analytical  costs  are  shown  in
Table 5.   At  a given level  of sensitivity, a  wide range of precision is  encountered  among
diverse  organic  compounds.   For  example,  the low  end  of the  range  of  variation  shown
for extractable  compounds  in  Table  5  can  usually be  achieved  for hydrocarbon  analyses,
whereas  substantially  more  variability  is  common for  analyses  of  phthalates  and  some
organic  acid  compounds.    A  wide  range   of analytical  costs  is  also  encountered  at  a
given  level  of  sensitivity   (Table  5).    Differences  in  analytical   techniques,   laboratory
experience  with  these  techniques,  and  pricing  policies  of  laboratories  account  largely
for the wide variation in cost.
QA/OC Program

     An  adequate QA/QC  program  is essential for  any sampling  and  analysis effort to
support exposure  assessment.  U.S. EPA  (1984c, 1985c)  provides  guidance on  QA/QC for
chemical analysis.  Tetra Tech (1986f) describes QA/QC procedures for field and laboratory
methods  used by the Section  301(h)  program.   Horwitz  et  al. (1980) provide guidance on
QA/QC  in  the analysis  of foods  for  trace contaminants.   Brown  et  al. (1985) describe
QA guidelines followed by NOAA for chemical analysis of aquatic environmental samples.

     A QA/QC  plan should be  developed as part of the  study  design for sampling  and
analysis of chemical residues.  The QA/QC plan should include the following information:

     •    Project objectives

     •    Project organization and personnel

     •    QA objectives for precision,  accuracy,  and  completeness for  each  kind
          of measurement

     •    Summary  of  sampling  procedures,  including  sample  containers,  prepara-
          tion, and preservation

     •    Forms for documenting sample  custody,  station  locations, sample  charac-
          teristics, sample  analysis request,  and  sample tracking  during laboratory
          analysis

     •    Detailed description of analytical methods

     •    Calibration procedures for chemical measurements

                                              39

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        TABLE 5.  APPROXIMATE RANGE OF COST PER SAMPLE FOR
           ANALYSES OF EPA PRIORITY POLLUTANTS IN TISSUES
          AS A FUNCTION OF DETECTION LIMITS AND PRECISION'

EPA Priority
Pollutant
Group
Approximate
Detection
Limit
Typical
Precision
Approximate
Cost Rangeb
Extractable
   acid/base/neutrals/
   PCBs/pesticides          <1-20 ppb

Volatiles                    <5-20 ppb

Metals                     100 ppb
<±5% - >±100%     $900->$2,000

<±IO% - >±100%    $250-5350

<±10% - >±30%     $250-$300
* NOTE:   Range of  per  sample cost  is  based  on multiple  quotes  compiled in
1986  for specific applications and >5 samples.   The  actual costs  may  vary  from
the  range  shown.  This information  is  provided solely for perspective on relative
differences  in cost and  should not be  interpreted as a recommendation of appropriate
costs for any given circumstance.

b Each cost  range  is  mainly  the result  of  laboratory  differences  in  technique
and pricing, NOT the range in precision or detection limits shown.

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     •     Internal QC checks for analytical laboratories

     •     Performance and system audits for sampling and analysis operations

     •     Preventive maintenance for equipment

     •     Procedures  for  data  management,  data  QA  review,  and  data  reporting
           for each kind of measurement

     •     Corrective actions

     •     Procedures  for  QA/QC  reporting and responsible  federal  and  state QA
           officers

     •     Mechanisms  for approval of  alterations  to  the monitoring  program, for
           suspending  sample  analyses,  and  for stopping sample analyses  within  a
           tiered design.

Relevant portions  of the  QA plan should be  incorporated in  the  statement  of work for
each contract laboratory involved in  sample analyses.


Documentation  and OA  Review of Chemical Data

     Adequate   documentation of  the  results  of chemical  analyses  are  needed  to ensure
proper  interpretation of the  data.   If  a  contract  laboratory is performing the  sample
analyses,  such   documentation should  be  specified  in  the  original  statement  of  work.
The documentation listed below is recommended for chemical residue data:

     •     A cover  letter discussing analytical  problems  (if any) and referencing  or
           describing the procedure used

     •     Reconstructed ion chromatograms for  GC/MS analyses for each sample

     •     Mass spectra of detected  target compounds  (GC/MS) for each sample

     •     GC/ECD and/or GC/FID chromatograms for each sample

     •     Raw data quantification reports for each sample

     •     A calibration  data  summary  reporting calibration range  used  (and DFTPP
           and  BFB spectra and quantification report for  GC/MS analyses)

     •     Final  dilution  volumes, sample  size,  wet-to-dry  ratios,  and  instrument
           detection limit

     •     Analyte  concentrations  with  reporting  units  identified  (to  two significant
           figures unless otherwise justified)
                                              40

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      •    Quantification of all analytes in method blanks (ng/sample)

      •    Method blanks associated with each sample

      •    Tentatively identified compounds (if requested) and methods of quantification
           (include spectra)

      •    Recovery   assessments  and  a   replicate  sample   summary  (laboratories
           should  report  all  surrogate  spike  recovery  data  for  each  sample;  a
           statement  of the   range  of  recoveries  should  be  included  in  reports
           using these data)

      •    Data qualification codes and their definitions.

The data  reporting forms for the EPA Contract Laboratory Program illustrate  an appropriate
format for documentation of chemical data.

      All  contaminant concentration  data to be  used in a  risk assessment should  undergo
a thorough QA review  by  a qualified  chemist independent of the laboratory that  analyzed
the samples.   In  some  cases,  the analytical  laboratory may provide  a QA  review that is
simply checked by an independent chemist.   The purpose  of  the  QA  review  is to evaluate
the data  relative  to  data quality objectives  (e.g., precision  and accuracy) and performance
limits  established in the QA  plan.    In  many cases,  qualifiers  are necessary for selected
data  values.   These  qualifiers should be  added  to the  database.   A  summary of  data
limitations  should  always   be  included  in   the  risk  characterization  (see   below,   Risk
Characterization).   The  EPA  Office  of  Acid Deposition,  Environmental  Monitoring,  and
Quality Assurance is  developing guidelines for quality assurance  of chemical data to support
exposure assessments.


Statistical  Treatment of Data

      Statistical  analyses  of  data will  depend  on  specific  study objectives.  For   each
species,  statistical  summaries  of tissue  concentration  data  should  include  sample   size,
estimates  of arithmetic  mean  concentration, range,  and  a measure of  variance  (standard
error  or  95 percent  confidence limits).  Geometric mean concentrations are appropriate
measures  of central  tendency  when only  estimates of  tissue burden of  contaminants or
exposure  dose  are desired.   However, arithmetic means  are  needed  to  compare  exposure
estimates  with  RfDs  and  to calculate health risk  for chronic  effects  because long-term
consumption is an  averaging  process.   Mean tissue concentrations and  variances  may be
calculated  for  mixed-species  diets  if data  are  available on  the   proportion  of  each
species in the diet.

      The  one-way  ANOVA  model  discussed  earlier  or multifactor  ANOVA  models  are
appropriate  for  testing  for  differences   in mean  contaminant concentrations  among
species, among sampling  stations,  or  among  time  periods (Schmitt  1981; also see Tetra
Tech  1986b,d).  For small  sample  sizes and  data  that  do not  satisfy the assumptions of
ANOVA,  nonparametric  tests such  as  the  Wilcoxon rank  sum  test for  two  treatments or
the Kruskal-Wallis  test  for multiple  comparisons  are  recommended.   These  tests   have
the added  advantage of being  relatively   insensitive  to  a  few  missing  data  points or
undetected  observations  (Gilbert 1987).   Long-term data  sets may  be tested for trends
by  time  series analysis  (for  reviews, see  Montgomery  and  Reckhow  1985  and  Gilbert

                                              41

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1987).    Examples  of trend  analysis  for chemical  contaminants  in  fish  are provided  by
Brown et al.  (1985)  for PCBs in striped  bass of  the  Hudson River and by  DeVault et al.
(1986)  for PCBs and DDT in lake trout from the upper Great Lakes.

     Data  on concentrations  of  contaminants  of  concern  in  tissue  samples  will  often
contain observations  below detection  limits.   Means and variances  for  tissue concentra-
tions  should  be calculated twice:   once  using detection limits for  undetected  observa-
tions  and  once  using  0   for  undetected observations.   Although  alternative  approaches
are possible (e.g., using one-half the detection limit), the approach recommended here yields
more   accurate,  complete  results  by  quantifying   the   range  of   the  estimated  values.
According  to  the  EPA  Exposure Assessment  Group,  calculations  of  plausible-upper-limit
risk  estimates based  on  detection  limits should  generally  be avoided.   However,  risk
estimates  based  on  detection limits  may  occasionally be  useful  to  indicate  that  particular
chemicals,  species,  or  geographic locations  are  not  problems,  even  assuming undetected
contaminants are  present at concentrations just below  their respective detection limits.

     The choice of contaminant concentration values to  use  in  subsequent  calculations
to estimate  exposure (and ultimately risk)  is partly  a risk management  decision.   Exposure
estimates  are  commonly  based  on  arithmetic  mean  concentrations  of  contaminants  in
edible  tissue  of  fish or  shellfish.   Use of  the upper  90 or  95 percent  confidence  limit
in place  of  the mean would provide  a  conservatively high  estimate of  exposure.  Calculation
of  conservative  estimates  for  exposure  is  an  appropriate  step  in  uncertainty  analysis.
However, U.S.  EPA  (1986b)  guidelines on  exposure  assessment  discourage  the  use  of
worst-case  assessments.   Use of  upper confidence limits  for  chemical  concentrations  in
combination  with  a plausible-upper-limit estimate  for  the  Carcinogenic  Potency  Factor
may lead to  an  unrealistic  (i.e.,  highly unlikely) estimate of  upper-bound risk,  especially
if a conservatively high estimate of  fish  consumption   is also adopted.   In  most cases,
the  best  estimate   of  exposure   based  on  mean  contaminant  concentrations should   be
used to  develop risk estimates.   If upper  confidence limits for  chemical concentrations
are used  to  develop risk   estimates, the effects of  compounding conservative assumptions
should be evaluated.
ANALYSIS OF SOURCES, TRANSPORT, AND FATE OF CONTAMINANTS

     Exposure pathways and routes are potential mechanisms  for transfer of  contaminants
from  a  source  to a  target human  population  or subpopulation.   The  sources,  transport,
and  fate of  chemicals  in  the  environment  are analyzed  to  evaluate exposure  pathways
and routes.   To compensate for  a  limited database, this analysis often includes  mathematical
modeling of contaminant  transport  and  fate.    The modeling  of  exposure  pathways
focuses  on  transfer  of contaminants  from  source  to target  fishery species,  since  the
transfer  step from  fishery to  humans can  be  based  on  knowledge of  fishery  harvest
activities (see below.  Exposed Population  Analysis).   When  extensive data on contamination
of a  fishery is  available  and  source-tracing is  not  an  objective,  modeling  of chemical
transport and fate may be unnecessary.

     Although the  specific uses  of  modeling  in  exposure assessment are  diverse, several
broad objectives may be outlined as follows:
                                              42

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      •    Estimate  the  spatial   and  temporal  distribution  of  concentrations   of
           chemical contaminants in edible tissues of fish and shellfish

      •    Identify potential sources of contaminants

      •    Evaluate alternative source controls or remedial actions.

Estimation  of contaminant  concentrations  in  fish and shellfish by mathematical  modeling
is especially  useful  when  available  data  on  tissue contaminants  are  limited.    If the
distribution of  contaminants  in  sediments or water  can be  estimated  from  available data
or model  predictions,  estimates  of chemical  residues in fishery species can  be  based  on
relationships  of  tissue  contamination  to environmental  contamination  (e.g.,  laboratory-
derived  bioconcentration  factors).   Spatial  characterization  is important  for  identifying
areas  of  high  contamination resulting  from  heterogeneous  transport  and  deposition  of
contaminants.     Temporal   characterization   is  important  for  defining  time-dependent
changes in contaminant concentrations that may mitigate future exposure and risk.

      Predictions  of  spatial  trends  in  chemical residues may  also aid  in  identifying and
controlling  sources of  pollutants.   For example,  when data  on  sources,  sediments,  and
tissues  are available,  modeling  of chemical  transport  and  transformation processes may
help  to  link the patterns  of  chemical  contaminants  observed  in  the  environment with
specific  individual sources.    Information on  differential degradation of contaminants and
compositional  relationships  for  complex  mixtures  can  be  used  to  support  the  model
analysis  (e.g.,  calibration and validation).   Finally, modeling of  contaminant  releases  in
combination with  chemical  residues in  fisheries may aid  in  evaluating alternative  source
controls  or remedial  actions  for waste  sites.   The  results  of modeling can indicate the
level  of source control or remedial action  needed to achieve a desired  level of environmental
quality.

      In  the exposure assessment guidelines, U.S. EPA (1986b)  describes general approaches
for  characterizing  sources,   exposure  pathways,  and  environmental  fate  of  chemicals.
Analysis of chemical transport  and fate  is a major endeavor, which cannot  be  addressed
in detail  here.    For  additional  information,  the interested  reader  should  consult  Callahan
et al.  (1979), Burns  et al. (1981), Jensen  et al. (1982), Mills  et al.  (1983), Games (1983),
Connor  (1984b),  Thomann   and  Connolly  (1984),  Onishi  (1985a,b),  U.S. EPA  (1986b),
Pastorok (1986), and references therein.


EXPOSED POPULATION ANALYSIS

      The  second  stage  of  the  exposure assessment,   analysis  of  exposed  populations,
includes the following steps:

      •    Identify potentially  exposed   human populations  and  map  locations  of
           fisheries harvest areas

      •    Characterize potentially exposed populations

           -  Subpopulations by age, sex, and ethnic composition
           -  Population abundance by subpopulation
                                               43

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      •    Analyze population activities

           -  Harvest trip frequency
           -  Seasonal and diel patterns of harvest trips
           -  Time per harvest trip
           -  General activity (e.g., clamming, crabbing, fishing)

      •    Analyze   catch/consumption  patterns   by  total  exposed  population  and
           subpopulation

           -  Proportion of successful  trips
           -  Catch  by numbers and weight according to species
           -  Time since last meal of locally harvested organisms
           -  Number of consumers sharing catch
           -  Parts of organisms eaten
           -  Method of food preparation (e.g., raw, broiled, baked)

      •    Estimate  arithmetic  average  consumption  rate by  species  and  by total
           catch  for  the  total  exposed  population  and for   subpopulations.   For
           seasonal   fisheries,  consumption  rates  may  be  estimated  on  an   annual
           and a seasonal basis.

      Only  selected  steps may  be performed in  a given exposure assessment, depending
on  data availability, study   objectives,  and  funding limitations.   Note  that  many of the
steps  to characterize harvest activities  and  consumption  rates  apply  only to  analyses  of
recreational fisheries.   When estimating consumption of  fish and  shellfish of commercial
origin,  harvest activities are  irrelevant.   Also, the specific geographic origin of commercial
fisheries products is often unknown.

      Two  approaches  to estimating   consumption  rates are  outlined below.   In  the  first
approach, a comprehensive analysis of a recreational fishery is performed based on extensive
catch/consumption data  for  the  exposed  population.   In the  second  approach, estimates
of consumption  rates are based  on available  values  for the  U.S.  population  (or  subpopu-
lations)  or  other  assumed  values.    Most  of the  available  estimates  were  derived   from
recall  or diary  studies (Lindsey  1986) and include commercial  fisheries  products.    It is
recommended here that  local or regional assessments of fishery  consumption  be performed
whenever possible to  avoid  possible  errors  inherent  in  extrapolating standard  values for
the  U.S.  population  to distinct  subpopulations.    Moreover,   extrapolation   of  standard
consumption estimates  that   include commercial fisheries  products  to recreational  fisheries
should generally  be avoided.

      In developing  a  profile  of  the  exposed  population,  there  is  no  single  "correct"
estimate of  consumption rate.   Because  consumption  rates  are highly  variable,  use  of  a
range of values or a probability distribution for consumption  rate  estimates is  recommended.
This  approach may  also be  followed  when estimating consumption  rates for subpopulations
of interest.

      An alternative  to  the typical  practice of basing risk  estimates  on selected  consumption
rates  involves  presenting  risk estimates  graphically  for a  wide  range  of  consumption
rates  that  essentially  includes  all  possible  realistic  values  (see  below,  Presentation  and
Interpretation  of Results).    For  example,  plots   of  estimated   risk  vs. consumption  rate
are useful  for  public advisories  on  recreational fishery resources.    In  this  case,  each

                                               44

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individual  may evaluate  risks by selecting a consumption  value  based on  his  or  her diet.
Use of  this approach  avoids having  to  collect  extensive data on the exposed population.
A similar  approach  involves  selecting an "acceptable" risk  level  and providing  advice  on
levels  of consumption,  such  that  the "acceptable"  risk  is  not exceeded.   The  advantage
of  both  of  these  approaches   is  that  consumption  rates  need  not  be  determined  or
assumed.   While  both may  provide excellent formats for advising sports  fishermen, they
may not be appropriate  in cases where  involuntary exposures are likely  (e.g., commercial
fisheries).
Comprehensive Catch/Consumption Analysis

     Appropriate  field  survey  forms,  data  analyses,  and  format  for  presentation  of
results  for  a  comprehensive  catch/consumption  analysis  of  fisheries  are  provided  by
Landolt  et al.  (1985),  McCallum  (1985),  and  National  Marine  Fisheries  Service  (1986).
Details  of  methods   will  not  be  presented  here,  except  to  emphasize  some  important
considerations  for calculating  consumption  rates.    Examples  analyses  of catch/consump-
tion data can  be found in Puffer et al.  (1982) for coastal  waters of southern California,
in Landolt et al.  1985, 1987) for Puget Sound,  in Helton et al. (1986) for New  York Bay
and Newark  Bay, and in National Marine Fisheries Service (1986) and companion documents
for other areas of the U.S.

     Lindsay (1986)  reviewed  alternatives  to  field  survey methods, including  use  of food
diaries and dietary recall.   Gartrell et al.  (1986a,b) described methods used  by  FDA in
their  total diet  studies to  estimate  rates of  consumption of various  foods.    However,
the results  of  the FDA  total  diet studies  are  of limited  use  in  the  present  context
because  fish  are  grouped  with  meat  and poultry.   Estimates   of  seafood  consumption
used by FDA  to  calculate  average intake of methylmercury for  exposed portions of  the
U.S. population were  based on a diary survey sponsored by the Tuna Research Foundation
(Tollefson and Cordle  1986).  Supplementary information on analysis of fisheries  consumption
data can be found in SRI (1980).

     The average rate  of consumption of  fish  or  shellfish  is the key exposure  variable
for use  in  subsequent  steps of  risk  assessment.  Consumption rates should be expressed
in terms of  g/day and meals/yr [meals/yr may  be calculated from g/day  by  assuming  an
average meal of  fish  or shellfish equals about 150 g  (0.33  Ib) if the  average  meal  size
is  unknown].   Average  consumption  rate  for  each  harvest species  is  calculated  from
field data according to the following steps:

     •     For  each  successful  angler  trip,  calculate  the  weight  of  harvest  by
           species based on number and total weight harvested per household

     •     Calculate mean harvest weight consumed per person per time by

           -   Dividing  the  total harvest weight for each  species  by  the .number  of
              consumers in household  and by the days  elapsed since last  meal from
              the same area
                                              45

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           -  Multiplying  the  value  obtained  in  the  preceding  computation  by  a
              factor   to  account  for  the  proportion  of  cleaned   weight  to   total
              weight  [according to Landolt et al. (1985), this  factor  equals about 0.5
              for squid  and crabs, 0.3  for  fish, and  1.0  for  shucked  clams;  these
              estimates should be verified or replaced by local data]

     •     Calculate  mean  consumption  rate  per person by geographic harvest  area,
           by subpopulation, and by total exposed population.

Note that  the above  method  (cf. Landolt et al.  1985,  1987)  may provide a biased estimate
of  average consumption  rate  due  to its  dependence  on  a  short-term  observation (i.e.,
time since last  meal).   Averaging of  data over a longer time period might  be  preferable,
but  such  data  may   be  more  susceptible to  biases  from  inaccurate  recall  of  consumers
(interviewees).    Harvest  weights  should generally  be  determined   directly rather  than
from  length measurements.  However,  for  shellfish  and crabs,  it  may  be necessary to
establish tissue weights from weight-length regression analysis.

     The  model for  calculating  mean daily consumption rate  (Ijjk)  for  fishery  species i,
human subpopulation j, and area k is therefore:

                                                   wijkl Pi
                                                                                        (4)
                                                   *jkl  Tjkl
where:
        I,jkl = Mean  daily  consumption  rate of  species i for  subpopulation j,  area k, and
              household 1 (kg/day)
       N;jk = Number of  households (successful  harvest trips)  for species i,  subpopula-
              tion j, and area k
       wijki " Weight of species  i  harvested  by household  1  of subpopulation  j in area k
              (kg)
         Pi = Proportion of cleaned edible weight of species i to total harvested weight
       Hjkl « Number of people in household  1 of subpopulation j in area k
       Tjkl = Time  elapsed since  last  meal  by household 1  of subpopulation  j in area k
              (days).

When consumption  rates (lyy)  are log-normally distributed,  a geometric  mean  consumption
rate  may  be  calculated  by  log-transforming  the  data  before  applying  Equation  4  to
calculate a mean  consumption rate.

     Consumption  rate  data  may be  summarized  further   by  calculating means  across
species,  subpopulations, and  areas.   However, it  should be  recognized that means of Iijk
across  species  do  not  represent  actual   diet  patterns  for  consumers  of mixed -species
diets.   To  calculate mean consumption rates for  mixed-species  diets, all  Ijjkl should be
summed across  species  within  a  household  before  determining  mean  consumption  rates
across households (Ijk):


                                                                                        /o
                                                                                        (5)
                                               46

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 Where:

         Ijk] -  Mean daily consumption rate of all  fishery species  for household  1, subpopu-
               lation j, and area k (kg/day)
        Njk »  Number of households in subpopulation j and area k

and other terms are defined above.

      Landolt  et   al, (1985)  summarized  the  assumptions  involved   in  calculating  mean
consumption rates (Ijjkl) by household as follows:

      •    Consumption

                PI values are assumed as noted above

                Catch was distributed evenly among consumers in house- hold

                People in household actually ate the entire cleaned  catch

                Personal harvest  consumption  was  distributed evenly  over the  time
                interval  since the last successful trip

      •    Fishing interval

                Fishing  frequency  (days)  is related to  seasonal  fisheries; that  is,
                interviewees  did  not  report  average  time interval  for  entire  year
                but only  for  recent  past.   Therefore,  calculated  consumption  rates
                cannot be directly extrapolated  to a yearly  basis.  Fishing  interval
                was set to  1 day if unreported (Landolt et al.  1985).

      Despite  the  limitation  noted  in  the  last  item  above,  calculated consumption  rates
can  be extrapolated to  an  annual average  rate by multiplying the Ijjkl  by 365 days  and
by  a  species-specific  factor  equal  to  the  fraction  of the  year  a  fishery  is available.
Determination  of  this  species-specific  factor  is  somewhat  subjective  because  of large
seasonal  fluctuations  of the  harvest  (e.g.,  Appendix £ of  Landolt  et  al. 1985).    These
factors should be determined on a case-specific basis.


Assumed Consumption  Rate

      In  many  cases,  comprehensive  data  on  fisheries catch  and  consumption  patterns
are not  available.   For  some  risk assessment problems  (e.g.,  ranking  of potential  problem
chemicals  in  aquatic  organisms   or  development  of  consumption   advisories)  extensive
catch/consumption data are  not needed.   Moreover,  catch/consumption patterns  undoubtedly
vary  over time.   Extensive  long-term  monitoring of  catch/consumption  for all areas  of
interest within a  large  water body may not  be  warranted.  Despite its obvious limitations,
extrapolating  consumption  data from one area (or  time) to  another  may  be a  suitable
approach when:
                                               47

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      •    Site-specific data are unavailable

      •    Differences among areas (or times) are expected to be small

      •    Precise  estimation  of average fish or  shellfish consumption  is  unneces-
           sary to meet the study objectives.

      In  the  past,  many  risk  analysts have simply  assumed  standard  values  for food
consumption rates  based  on previous analyses  of dietary patterns  of  the  U.S. population
(U.S. EPA  1980b;  SRI  1980).  Average values  for fish  and  shellfish  consumption  for  the
U.S. population  generally  range from  6.5  to  20.4 g/day (Nash  1971;  National  Marine
Fisheries  Service 1976,  1984;  SRI  1980; U.S.  Department of Agriculture   1984; also  see
Appendix  F).   Most   estimates  include   fish   and   shellfish  (molluscs,   crustaceans)   in
marine,  estuarine,  and  fresh waters, but  saltwater species  form  the bulk of  consumed
items.   Most  estimates  also  include  commercially harvested fisheries  products.    Also,
estimates  of average  U.S. consumption  do  not  account  for  subpopulations in  areas such
as the Great Lakes that consume large quantities (>20 g/day) of  locally caught sport fish.

      An  estimate   of  6.5 g/day  for  consumption   of   commercially  and  recreationally
harvested fish  and  shellfish  from  estuarine  and  fresh   waters  was  used  by  U.S. EPA
(1980b)  to  develop water quality criteria  based  on human  health guidelines.   The value
of 6.5 g/day  is  an  average per-capita  consumption rate for  the U.S.  population, including
nonconsumers,  based  on  data  in  SRI  (1980).    Consumption  rates   for  portions   of  the
U.S. population  (e.g., by region,  age, race,  and  sex) show  that  average  consumption  of
fisheries organisms  may  vary from  about 6  to  100 g/day  (e.g., Suta 1978;  SRI 1980;
Puffer et al. 1982).   Finch (1973) determined that approximately 0.1 percent (i.e., the 99.9th
percentile)  of  the  U.S. population  consumes  165 g/day  of  commercially  harvested  fish
and  shellfish.  Pao et al.  (1982) provided  estimates of 48 g/day for  the  average and  128
g/day for  the  95th percentile  consumption rates  by U.S.  consumers of fish and shellfish.
Rupp  (1980)  presented  estimates  of  average  daily  consumption   of  freshwater fish,
saltwater  fish,  and  all  shellfish according  to age  group  within  the U.S. population.  SRI
(1980) presents  average and  95th  percentile rates  of  consumption  of all  fish and shellfish
according  to  age  group,  race,  region  and  other demographic  variables.   Estimates  of
food  consumption  rates  for  specific subpopulations in the U.S. are also available  from  a
database maintained  by the EPA Office of Pesticide  Programs (see Appendix F).   Limita-
tions of fisheries consumption data are discussed by SRI (1980) and Landolt et al. (1985).

      One or  more  of the following values of  average consumption rate may  be assumed
when site-specific data are unavailable:

      •    6.5  g/day to  represent  an estimate  of  average consumption  of fish and
           shellfish  from  estuarine and fresh  waters by the U.S.  population  (U.S. EPA
           1980b)

      •    20 g/day  to  represent an estimate  of  the average  consumption of fish
           and   shellfish  from  marine,  estuarine, and  fresh  waters by  the  U.S.
           population [U.S. Department of Agriculture (USDA) 1984]

      •    165 g/day to  represent  average  consumption  of  fish  and  shellfish  from
           marine,   estuarine,  and  fresh   waters  by  the  99.9th  percentile  of  the
           U.S. population (Finch 1973)


                                              48

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      •    180  g/day to represent  a "reasonable worst case" based on  the  assumption
           that  some  individuals would consume fish at  a  rate equal to the combined
           consumption  of red  meat,  poultry, fish,  and shellfish in the U. S.  (EPA
           Risk  Assessment  Council  assumption  based  on  data  from   the  USDA
           Nationwide Food Consumption  Survey of 1977-1978; see Appendix F).

Extrapolation  of  these   values  to  local  populations   and  recreational   fisheries   should
generally be  avoided.   Limited  estimates of  average  consumption rates  for  recreational
fisheries are given  in SRI (1980).   Whenever possible, data on  local consumption patterns
should  be collected  or  obtained  from  a  current database.   Alternatively,  risk estimates
may  be expressed  on  a  unit  consumption  basis (i.e.,  per  unit weight  of fish/shellfish
consumed).   This latter  approach  is used by some  states in issuing sportfishing  advisories.
If average  consumption  values  listed above  are assumed   for local risk   assessment, it  is
recommended that  a range  of values be  used.   The  references cited earlier  should be
consulted for consumption  rate  data  for  fish and  shellfish  separately, or  for  individual
species (also see references cited in Appendix F).


EXPOSURE  DOSE DETERMINATION

      In  the next  step  of the exposure  analysis,   information  on  estimated contaminant
concentrations  and  rate  of consumption of  fish and shellfish  are  combined to  estimate
chemical intake  by exposed  humans.   Analyses of  single-species diets and mixed-species
diets  are discussed separately in the following sections.


Single-species Diets

      The general model to calculate chemical intake for a  single-species diet  is:

                                   Qkm *ijk Xm
                           Eijkm "        y/                                            ^

where:

      Eijkm  * Elective   ingested dose  of  chemical  m  from  fishery  species  i  for   human
              subpopulation j in area k (mg kg'1 day"1 averaged over a 70-yr lifetime)
      Cikm  « Concentration of chemical m in  edible portion  of species i in area k (mg/kg)
        Ijjk  « Mean  daily  consumption   rate  of  species i  by subpopulation j  in   area k
              (kg/day averaged over 70-yr lifetime)
        Xm  * Relative absorption  coefficient,  or  the ratio  of  human absorption efficiency
              to test-animal absorption efficiency for  chemical m (dimensionless).
         W  » Average human weight (kg).

Values  of  subscripted   terms  above  may be  estimated   means or  uncertainty  interval
bounds  (e.g., 95 percent confidence intervals) depending  on  the exposure  scenario  being
modeled (e.g.,  worst  case vs. average  case  vs. lower-limit  case).   Note  that Egkm  is
analogous to  the dose  "d" in  Equations  1  and 2.   The term "effective"  ingested dose
(Ejjkm)  is introduced  to  emphasize  that  estimates of  chemical intake (i.e.,  ingested dose)
may  be  modified by the term  Xm to account for  differential absorption  of contaminants
by humans and bioassay animals.


                                              49

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     Absorption coefficients  (Xm)  are  assumed  equal  to  1.0  unless  data  for  absorbed
dose  in animal bioassays  used  to  determine  toxicological  indices  (carcinogenic  potency
or  RfD)  are  available  and  the human  absorption  coefficient  differs from  that  of  the
animal  used  in the  bioassay.  Assuming that  Xm  is  equal  to 1.0  is equivalent to  assuming
that the human absorption efficiency is equal to  that of the animal  used in the  bioassay.
In  the  absence of  data  to  the contrary,  this  is  appropriate.   Toxicological  indices  are
determined  from  bioassays that usually  measure  administered  (ingested) dose.  Therefore,
the estimated  chemical  intake  by  humans, Ej:km,  is usually the  ingested  dose,  not  the
absorbed dose.  If  the  toxicological index  used  to  estimate  risk  is based  on the  absorbed
dose,  then an estimate  of human absorption efficiency  for  the chemical  of concern  may
take the place of the term Xm  in Equation 6 above.   In most cases,  however, information
or  assumptions about absorption efficiencies has  been  incorporated  into  EPA's  estimates
of  RfDs  and  Carcinogenic  Potency Factors.    Therefore,  Xm is usually  dropped  from
Equation 6 and Eljkm becomes simply  the ingested dose.

     W  is  usually  assumed  to  be  70 kg  for   the  "reference  man" (U.S.  EPA  1980b).
Assuming  other average  values  to  account  for  growth from a  child's  body  weight  to
adult  weight  over  a lifetime  would  not  change  the  results  of  carcinogen risk assessment
substantially.   Concerns about  exposures  over a time  period of  less than about  IS  yr
may require  modeling  of early childhood  exposures.    Standard  values  for age-specific
body  weight  and  other factors  used in  exposure  assessment  are  provided  by  Anderson
et al. (1985).
Mixed-species Diets

     Estimation  of  chemical  exposure  due  to a  mixed-species  diet  is complicated  by
variation  in the  dietary habits  of  individuals.   The various diets of  individual  humans
may differ  from  one  another  in the  kinds  and  relative  proportions  of fishery species
consumed.   The  sum  of  species-specific  exposures (Ejjkm) is  not  equivalent  to  total
exposure  for a  mixed-species diet.   In  a diverse  fishery, each  individual  consumer  is
likely  to consume  only a  subset of  the total  available  species.   Thus,  the    sum  of
species-specific  exposures  might  overestimate  the  average  consumption   rate  for  mixed-
species diets.

     To  estimate  average  chemical  exposure resulting  from  a  mixed-species  diet,   an
exposure dose should first be estimated for each individual in a subpopulation as follows:

                                         EMkro
                       «j.»               	
where:

      Ehjkm * Effective exposure dose  of chemical m from  a mixed-species diet eaten  by
              individual  human h  in subpopulation j in  area k (mg  kg'1 day'1 averaged
              over a 70-yr lifetime)
       Ihijk • Average consumption rate of  species i by  individual h in  subpopulation j
              in area k (kg/day averaged over a 70-yr lifetime)

and  other terms are  defined  as  above.   The average  exposure dose  for mixed  species
diets is:

                                               50

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where:

       Ejkm * Average  effective  exposure dose  of chemical m  from  mixed-species diet
              for subpopulation j in area k (mg kg"1 day1)
        Hjk - Number of persons in subpopulation j in area k.

Uncertainty estimates can be obtained by calculating 95 percent confidence limits for E:km.


SOURCES OF INFORMATION

      References  to  protocols  for  sampling   and analysis  of toxic chemical  residues  in
fish and  shellfish  are  provided  above  (see Tissue Concentrations of Contaminants).  For
the  updated status of protocols and  new  developments, contact a representative  of the
EPA  Office of Water (Appendix A) or one of  the  EPA Office of Research and Development
Laboratories (Appendix G).   Information on sampling and  analysis  of  commercial fisheries
products collected  from  the  marketplace  is available in FDA Compliance  Program Guidance
Manuals  (available  from  FDA,  Freedom of  Information  (HFI-35),  5600  Fishers  Lane,
Rockville, MD 20857).

      Compilations  of  data  on  concentrations  of  chemical  contaminants  in  fish and
shellfish are available in  the  EPA Ocean Data Evaluation System  (ODES),  reports  of the
NOAA  Status  and Trends  Program  (e.g., Matta et al.  1986),   Tetra  Tech  (1985b), and
Capuzzo  et  al.  (1987).    For  current local  information,  contact a member of the  EPA
Regional  Network for Risk  Assessment/Risk  Management  Issues  (Appendix  H).    Many
state  health  and environmental  agencies  maintain  regional databases on chemical residues
in  fish and shellfish.   For  example, the New  York State Department of  Environmental
Conservation  and  the  New   Jersey  Department  of  Environmental   Protection  publish
periodic reports  on contaminants levels in fish (e.g.,  Armstrong and Sloan 1980;  Belton
et  al.  1983; Sloan and  Horn 1986).    The  Wisconsin  Department of  Natural  Resources
(Bureau  of  Water Quality) maintains  computerized records of  long-term  data on  PCB
concentrations in  fish of the Great Lakes.

      Summaries of data on  contaminant concentrations in a variety of  foods are available
in Grasso and  O'Hare (1976), Lo  and Sandi  (1978),  Stich  (1982),  U.S. FDA  (1982), and
Vaessen et al. (1984).  FDA  is developing a data system called FOODCONTAM for pesticide
and industrial contaminant  residues in foods.

      References  containing  estimates  of the  rates  of consumption of  fish and shellfish
by  the U.S. population  were presented above  (see Assumed  Consumption  Rate).    The
EPA  Office of  Pesticide  Programs  maintains  the Tolerance Assessment System (Saunders
and   Petersen  1987).    The  Tolerance  Assessment  System uses  a  U.S.   Department  of
Agriculture  database  (based  on  a 1977-1978 survey) to  generate  estimates of consumption
of  various  foods  stratified  by  specific  subpopulations (e.g., infants, children,  and  adults
in the  northeastern U.S.).  The  Office  of Pesticide Programs  is  also developing informa-
tion on  the effects of food  preparation methods on chemical residues in food.
                                              51

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                              RISK CHARACTERIZATION


     In  the  risk  characterization  stage, results  of  the  hazard,  exposure and the  dose-
response  assessments  are combined  to  estimate  the  probability  and  extent  of  adverse
effects  associated  with  consumption  of contaminated fish  or shellfish.   An  overview  of
the  risk  characterization  process  is  shown  in  Figure 6.   In  human  health   risk assess-
ment,  carcinogens  and  noncarcinogens  are  treated  separately.   Indices of  risk  for  these
different  categories   of  toxicants  are  based  on   different dose-response   models  (see
above, Dose-Response Assessment).

     The procedures  for generating  quantitative estimates  of risk  are  emphasized in  the
following sections.    However,  it  is  critical that  numerical  estimates  of  risk  not  be
presented in  isolation  from  the assumptions and   uncertainties  inherent in  the process
of risk assessment.   The risk characterization should  include a discussion of assumptions
and  uncertainties and their potential  impact on numerical estimates of risk; i.e., the degree
to which the  numerical  estimates are  likely to reflect  the actual  magnitude  of risk  to
humans.  For example,  if  upper confidence  limits  for  mean  chemical concentrations are
used  to  develop risk estimates,  the  effects  of  compounding assumptions of  upper-bound
estimates  of  carcinogenic  potency  and  conservatively  high  estimates  of  consumption
rate  should  be  evaluated.    A  risk  characterization  should include  a  summary of the
preceding  steps  of  the  risk  assessment:    hazard   assessment,   dose-response  assessment,
and  exposure  assessment.   The  weight-of-evidence  classification  and  other supporting
information  should be  summarized  concisely.   Approaches  to presentation  of  summary
information  to  be  included  in  risk  characterization  are  presented  in  the  next chapter
(see  below, Presentation and Interpretation of Results).


CARCINOGENIC RISK

     Numerical  estimates of  carcinogenic  risk  can  be presented  in  one or  more  of the
following ways (U.S. EPA 1986a):

     •    Unit  risk   -  the   excess  lifetime  risk   corresponding  to  a  continuous
           constant lifetime  exposure to a unit carcinogen concentration (e.g.,  1  mg/kg
           carcinogen in edible tissue of fish  or shellfish)

     •    Dose  or concentration corresponding  to   a  specified  level  of risk  -  for
           example, a guideline for maximum allowable  contamination of a specified
           medium may  be  derived from  a maximum allowable  risk value established
           by risk  managers

     •    Individual  and population risks -  upper-limit estimates  of excess  lifetime
           cancer  risk may  be expressed for  individuals  (as a probability estimate)
           or for  the exposed population (as an  estimate  of the  number of cancers
           produced within a population of specified size per generation).
                                               52

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1 Ha.
1 Identrti
lOOM-R
1 Asses
i
urti 1
-anon 4 L
esponsel^
smenl |
p










Physical-Chemical
BioaccumulatBn Potential
Environmental Partitioning,
Degradation. Transport
Mechanisms, and Potential
Exposure Media
Metabolism and
Pharmacokineuc Properties
Tone Effects in Humans
and Laboratory Animal*
















e.g., Structure-Activity
Relttionsnips. K^.
Bioconcentration Factors
e.g., Air, Water, Sediment,
and Biota
e.g., Upopnilicrty. aoactivalnn,
Tonlication/Oetoiification,
Target Organs. Ekminaicn
e.g.. Acute and Chronic
Toiicrty, Carcinogenic Potency,
Ep()erniologic Evidence
e.g., Dose-Response Relations,
Carcinogenic Potency
e.g., Adequacy and Quality
of Data, bkelinood of
Specific Tone Effects
   Are Data
 Sufficient For a
Quantitative Risk
 Assessment?
    Is Substance
     Potentially
     Hazardous'












Select Route of Exposure

Concentration of
Specific Contaminant






oQoy WttQhf of
Exposed Indvidual
















e.g., in g/day of nsrvSneilfisn
Consumed
e.g., Vea/1 of Exposure,
Fraction o« lifeline Exposed
e.a.. Assimilated
Contacted
Daily Exposure Per kg
BodyWeignt
                                       Qualitative Risk Determination Based on
                                   Toxieoteggal Properties and LrnHed Exposure Data













• Carcinogenic Potency
•HFD
• Other Standards

• ProoaWty of Tumor
• CxMSdanne of Standard
• Procaoikty of Some Other
Adverse Health Effect
Figure 6   Conceptual structure of quantitative health risk assessment
             model.

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Regardless of  the  option  chosen for expressing risk,  final numerical  estimates  should  be
presented  as  one   significant  digit  only,  followed   by  the  EPA  classification  of  the
weight of evidence  for carcinogenicity in brackets (U.S. EPA 1986a).

     The general  model for estimating  a plausible upper limit  to  excess  lifetime risk of
cancer at low doses for a single-species diet is:

                                  R ijkm * fll m Eijkm                                 (9)

where:

     R'ijkm • Plausible-upper-limit  risk  of  cancer  associated with  chemical m  in  fishery
              species i for human subpopulation j in area  k (dimensionless)
       q/n, « Carcinogenic Potency  Factor  for chemical m  [(mg kg'1  day'1)"1]  estimated
              as the upper 95  percent  confidence limit  of  the slope of a  linear  dose-
              response curve
      Eijkm * Exposure  dose  of chemical  m from species i for  subpopulation  j in area k
              (mg  kg'1 day'1)

The  actual   risk is likely  to  be  below  the estimated  upper-limit  value  calculated  from
Equation  9,  and may be  zero  in some  instances.   Equation  9 corresponds  to Equation 2
above,  except   that an  estimate  of human exposure (E^)  has replaced  the dose  (d),
which  is usually  a  known quantity administered  to a  bioassay  animal.    All Ejjkm are
calculated  as discussed  above  (see Exposure Dose Determination  in  Exposure  Assessment).
When  local  consumption  rate data  are  unavailable,  a range  of E^km and corresponding
risk  estimates   may  be  calculated  based  on  a   range   of  assumed  consumption  values.
Estimates of q,*m  are available in IRIS.   Note that Equation 9 is only valid for estimated
risks below 10.

     Estimation  of  upper-limit  risk   associated   with   the  average   mixed-species   diet
follows  a  similar  approach,  except that  the  average  effective  dose   (Ejkm)  of chemical
m from a  mixed-species diet,  calculated  from  Equation 8  above, replaces  the  species-
specific  exposure  (Ei;km)  in  Equation 9.   Calculation  of the average  effective dose  was
discussed earlier (see Exposure Assessment, Exposure Dose  Determination).
NONCARCINOGENIC EFFECTS

     Noncarcinogenic  risk  may  be  evaluated  by  calculating the  ratio  of the  estimated
chemical intake to the RfD as follows:
where:
                                     Hijkm-  575-                                   do)
      Hijkm " Hazard  Index  of  a  health  effect  from  intake  of  chemical m associated
              with fishery species i for human subpopulation j in area k (dimensionless)
     RfDm » Reference Dose for chemical m (mg kg"1 day'1)

and Eijkm is defined as above.  RfDm values are given in  IRIS  (U.S. EPA 1987a).
                                              53

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      When  all  significant  exposure  routes  and  sources  are  taken  into  account,   the
estimated  total exposure  for all routes  replaces  Eijkm in  the  numerator  of  Equation  10
and the  resulting  hazard  index is  compared  to  a  value of  1.0  to evaluate the chemical
hazard  (Stara et  al. 1983;  U.S. EPA  1985b).   Values  of  the  hazard   index  for  total
exposure  or of H;jkm that are above  1.0 indicate  that  the  estimated exposure is potentially
of  concern.   Above  1.0,  increasing  values  of  either  hazard  index  indicate increasing
hazard.   However,  the  hazard  index does  not define  a  dose  response  relationship,  and
its  numerical  value should not be regarded as a direct estimate of risk.

      Because  Hijkrn as  calculated  by Equation  10 do  not  account  for  exposures other
than  that  from  consumption  of  single   fisheries  species,  values  of  Hjjkm  substantially
below  1.0  do not  necessarily  indicate  a  lack  of  significant  risk  overall.    Although
species-specific hazard  indices  are useful for evaluating  whether  contamination  of  any
single species is of concern, two problems remain:

      •     How can hazards from mixed-species diets of fish and shellfish be  evaluated?

      •     How should  exposures from sources other  than consumption of  contami-
           nated fish and shellfish  (either single-species or  mixed-species  diets) be
           taken into account?

      To  address  the first  question above, one approach  would  be to sum  Hjjkm  values
across  all species   to  obtain a hazard  index,  Hjkm,  associated  with  the  entire  fishery.
However, Hjkn, could not be interpreted  as representative  of actual hazard  to individuals,
since the  sum of estimated  exposures across  species  will  not be the same  as  exposures
associated  with the  mixed-species  diets of individuals  (see  above, Exposure  Assessment,
Exposure  Dose Determination, Mixed-species Diet).   An  alternative approach recommended
here  is to  use the  average  effective dose (Ejkm)  for mixed-species  diets  to calculate  a
hazard  index.   This  hazard  index  for   mixed-species  diets  still  does  not  account  for
exposures due to other sources.

      To  address   the  second  question  above,  the sum  of  exposures from  all  sources
should  be  compared  to  the  RfD  to  evaluate  total hazard.   Guidance on  estimation  of
exposures due to  other sources is available in  U.S. EPA (1986b,f).   If exposure estimates
for sources other  than  the  fishery are  not available, then  some  relatively  small fraction
of  the  RfD (e.g.,  0.1) could  be assigned to intake  from  consumption of fish and shellfish.
This  fractional RfD would  then  replace  the RfD  in  the denominator  of  the  hazard
index.  The  index  would  be  compared  to a  value  of  1.0 to  evaluate  the potential  for
concern.   However, the  uncertainties  associated with  such an approach should be clearly
stated.  Further research on this  problem is clearly needed.

      The margin   of exposure  (MOE) is an  alternative  indicator  of noncarcinogenic risk.
The MOE is  the  ratio of the No-Observed-Adverse-Effect-Level to an estimated exposure
dose.     When the MOE  is equal  to  or greater than  the  product  of the  uncertainty
factor and  the modifying factor  used to derive the RfD,  the level of regulatory concern
is  usually low (see  U.S.  EPA  1987a for details  of  the  derivation of RfDs).   Concerns
about  mixed-species  diets  and exposures  from  non-fishery sources,  as  discussed  above
for hazard indices,  also apply to  MOE for exposure  to contaminated fisheries.
                                               54

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CHEMICAL MIXTURES

     U.S.  EPA  (1986d) discussed  various models for  assessment  of  the  upper  limit  to
risk  from  chemical mixtures.  Because  of present data limitations and the complexity  of
possible contaminant interactions, it is  virtually  impossible  at present to predict synergistic
or  antagonistic  effects  of  most  chemical  mixtures.   Moreover,  such effects  may  be
unlikely  at  low environmental  concentrations  of contaminants.  The  approach  used  most
frequently   for  multiple-chemical  assessment  is  the  additive-risk  (or  response-additive)
model.  Thus,  total  upper-limit  risk  for a  chemical  mixture  is usually estimated  as the
sum of  upper-limit risks  for carcinogens or  of  hazard  indices for  noncarcinogens.  A
sum of noncarcinogenic hazard indices should be  calculated only for a group  of chemicals
acting  on  the  same target organ  (Stara  et  al. 1983).   The numerical  estimates  obtained
using  the   response-additive  model  are  useful  in  terms  of   relative  comparisons  (e.g.,
among  fishing  areas  or among  fishery species).  However,  risk  estimates  for  chemical
mixtures should be  regarded only as  very  rough  measures of absolute  risk  (U.S.  EPA
1986d).   Because  technological  limitations  preclude   analyzing  fishery  samples  for  all
potentially  toxic  chemicals,  risk  estimates  for  chemical  mixtures  should  not  be  inter-
preted  as estimates  of total chemical risk associated with ingestion.
                                               55

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                 PRESENTATION AND INTERPRETATION OF RESULTS


      Examples  of  formats  for  presenting  the  results  of  risk  assessments are  provided
below.   These  formats are  adaptable  to  any level  of summary analysis  (e.g.,  subpopula-
tion  vs. total  exposed  population,  individual  fishery  species  vs. average across species).
Approaches  to  presentation  of supporting  documentation on assumptions and  uncertain-
ties  are  also  described.     Interpretation  of  the  results is  largely  a  function  of  risk
management.   As  such, guidance  on  interpretation  of risk  estimates  to support  decision -
making  is  beyond  the scope  of  this manual.   Nevertheless, a  brief  discussion of  risk
comparisons (e.g.,  estimated risks for various  fish  species;  estimated  risk  vs.  acceptable
risk defined  by  policy)  is  provided  to alert  the  reader  to the interface between  risk
assessment  and  risk  management.   Supplementary  information,  such  as  comparisons  of
contaminant concentrations  with FDA  action levels, is addressed in the final section below.


PRESENTATION FORMAT

      The  results of  risk  assessment  may  be  summarized  in  both  tabular  and graphic
format.   All  final  estimates of risk  should  be rounded to  one significant  digit  (or an
order  of magnitude  if appropriate).    The EPA  classification  of the  qualitative  weight of
evidence  for  carcinogenicity should  be shown in brackets adjacent  to final risk estimates
for carcinogens (U.S.  EPA J986a).  To guide the reader's interpretation  of the information
presented,  supporting  text  should  describe  assumptions, uncertainties,  and   any  caveats
about  the  results    All risk  estimates  should  be  interpreted  as plausible-upper-limit values
for the stated assumptions and exposure conditions.


Summary Tables

     An  example  format  for  summarizing  an  exposure analysis  is  shown   in Table 6.
The table  format  allows  storage  of  quantitative information in  a  computer  spreadsheet.
Columns  of notes containing  references  to sources  of  information  can  easily  be added
to the spreadsheet to further document the exposure analysis.

     It  should   be  emphasized  that   some of  exposure  variables  are  capable   of  being
measured  relatively  precisely  (e.g.,   contaminant concentrations  in  fish  tissue),  whereas
others may  only be  estimated  on  an order-of-magnitude  basis  (e.g.,  consumption rate).
The  precision  and  accuracy  of  the  final  risk  estimates  are  directly  related  to  the
precision and accuracy of the  variables incorporated  into the equations  used  to calculate
exposure and risk.

     Quantitative uncertainty analyses such  as  sensitivity  analysis  are  easily  performed
with  a spreadsheet by calculating exposure estimates  for low,  mid, and high  values of
key   variables   within  their respective  plausible  ranges.    Specification  of  probability
distributions for key  variables  is  an  alternative method  of uncertainty analysis  requiring
graphical models  (see  below, Uncertainty Analysis).   In  the  example shown  in  Table 6,
the  average,  minimum, and maximum  concentrations  of  each  contaminant [PCBs  and
mercury (Hg)J are  used to estimate potential health risk,  thereby accounting  for uncertainty

                                               56

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                   TABLE 6.  EXAMPLE TABULAR FORMAT FOR DISPLAY OF QUANTITATIVE RISK ASSESSMENT FOR CONSUMPTION OF FISH AND SHELLFISH


Substance
PCBs


PCBs


Mg


Hg


r 	
Concen-
tration
in Medftn
(mg/kg>8
0.007
O.OM
0.010
0.007
0.004
0.010
0.157
0.008
0.478
0.157
0.008
0.478

Contact
Rate
|
None arc inogens

RfD
(mg/kg/d)
N/Ad
N/A
N/A
N/A
N/A
N/A
2.9E-04
2.9E-04
2.9E-04
2.9E-04
2.9E-04
2.9E-04

Hazard
Index
N/A
N/A
N/A
N/A
N/A
N/A
5E-02
3E-03
2E-01
2E-01
8E-03
5E-01
8 Concentration of contaminant in fisheries species of concern (ing/kg = ppn by mss, wet weight).

k Amount of fish/shellfish ingested per day, prior to accounting for absorption efficiency,  etc.

c Ratio of g of contaminant absorbed per g of contaminant ingested, or correction factor to account for differential  absorption by humans and
bioassay animals (see text. Exposure Assessment. Exposure Dose Determination).

d N/A = not applicable.

e Carcinogenicity of methyl Hg has not been evaluated by EPA Carcinogen Assessment Group.   Hg is typically treated as a  noncarcinogen  in risk
assessment.

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in  chemical  analyses.   Also,  risks  are  estimated  for  two  consumption  rate  estimates
(6.5 g/day  and 20 g/day).   Note that spreadsheet summaries of  quantitative information
should  be supported  by a  text  discussion of  qualitative  uncertainties  such as  the  weight
of evidence for the health effect of concern.


Summary Graphics

      Presentation of risk assessment results in graphic form may include:

      •     Plots of estimated risk vs. consumption rate

      •     Plots  of estimated  risk  vs. contaminant  concentration  in edible  tissue  of
           fish or shellfish

      •     Summary maps  of  risk  estimates  for  different  geographic  locations  or
           individual sampling stations

      •     Histograms  of estimated  risk  by  fishery species,  human  subpopulation,
           or geographic location.

Because  estimated  risk  for a  given  area  and fishery species  varies  with   consumption
rate  and  because  consumption  rates  vary  greatly  among  individual  humans,  the  first
approach  above  is  recommended  as  a primary  means  of  presenting  risk  assessment
results.    Actual  consumption  patterns  of the  exposed  population  may  or  may  not be
estimated (see above,  Exposure  Assessment).  If they are,  estimates of average consumption
rate (and  95  percent  confidence  limits)   can be identified  in  a  footnote  (e.g.,  Figure
7).   Uncertainty in  chemical measurements can be illustrated by plotting lines  corresponding
to  the  minimum  and  maximum  (or  95  percent  confidence  limit) values of contaminant
concentrations in  fishery  species,  as  well  as the  mean concentration  (e.g.,  each  solid
line in   Figure  7).   As  an interpretive  aid,  risk  assessment  results for  a  reference  area
can  be  presented  along  with  those  for the  study area.   Coupled  with information on
comparative  risks  (see  below,  Risk  Comparisons), Figure 7  is an  appropriate  format  for
graphic display of results to lay public.

      Other approaches  noted  above can  be  used to supplement plots  of risk  vs. consump-
tion.    Summary   maps  and   histograms  may  be  especially  useful  for  presentation  of
detailed  results of  spatial  analyses  by  human subpopulation or  by  fishery species.   Plots
of  risk  vs.  contaminant concentration  for  selected  consumption  rates  and   species  (e.g.,
Figure 8) aid in rapid interpretation of tissue contamination data.


RISK COMPARISONS

      Interpretation  of carcinogenic risk  assessment  results  may be based on  comparison
of estimated health risks for  the study area with:

      •     Estimated health  risks  for consumption of fishery  species  from a reference
           area

      •     Estimated health  risks  for consumption of alternative foods (e.g., charcoal-
           broiled steak,  marketplace foods).

                                               57

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           cr
           cr
           111
         CD
           LU
           s
           LL
                 10-3-
10"*-
10'5-
                 10-6-
                 10
                  •7
                          STUDY AREA
                          N . 25 BUTTER CUMS
                                               REFERENCE AREA
                                               N - 25 BUTTER CLAMS
                      1
                     (2)
                    10
                   (25)
  I
 100       g/day
(250)     (m«al*/yr)
                                  CONSUMPTION RATE
PCBs Weight-of-evidence elMsifiettion:
    PROBABLE HUHAM CARCINOGEN [82]

All  canctr ri*ks are  pt«usiblt-hpper-limit  tttiMttc  of  txctsc  ritk  btctd  on
linearized nultittage procedure and assumptions sumarized  in the text.  Solid lines
are  risks  associated with  average PCS concentrations in  butter clams.  Dashed lines
are  for   uncertainty  range  (e.g.,  95  percent  confidence  Knits)  for  average
concentrations of PCBs, not the  total uncertainty.  Actual  risks are likely to be
lower than those shown above and ny be zero.
   Figure 7   Example graphic format for display of quantitative risk
               assessment results for hypothetical study area and reference
               area.

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     10-* r-
cc
LLI
o
z
<
o
UJ
:  R;*. REFERENCE
                                       C" -TISSUE CONTAMINATION

                                          GUIDELINE FOR S.Sg.day
                                           11    I  I t t i I i t I   I  I  i i i i i i I
                      CHEMICAL CONCENTRATION IN

                         FISH OR SHELLFISH (ppm)
      Figure 8  Plausibfe-upper-limit estimate of lifetime excess cancer n'sk
               vs. concentration of a chemical contaminant in fish or shellfish

               (ppm wet wt.) at selected ingestion rates.

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An  example  of  comparison  with  reference-area  risk  estimates  is  shown  in   Figure  7
above.  Comparative risks for alternative  foods  can be summarized in a table or  histogram.
Wilson  and  Crouch  (1987) point  out  the  importance of  comparing the  results of  risk
assessments   with  similar assessments of common  activities  to  provide   perspective  for
interpretation of the results by risk managers and the general public.

     Risk comparisons should be based on consistent exposure analysis  and risk  extrapolation
models.  Analogous  exposure scenarios should be used for  each risk estimate  being compared
(i.e.,  either  worst case,  plausible-upper  limit,  average,  or lower  limit).   A single  mode!
should  be  applied  consistently  to  calculate exposure and   risk.   A linear  extrapolation
model,  such  as   Equations  2  and  6 above,  is  justified  in  general  if  the excess  risk
attributed  to the  contaminant   of concern  is  regarded  as  a  marginal  risk,  added  to a
background of relatively high  cancer incidence from all other causes  not  being modeled
(Crump et al. 1976; Omenn  1985).

     When  interpreting  the  results  of  risk  assessments,  risk  managers  may  define  an
acceptable  level  of risk  to provide  a  criterion for  judging the  significance  of potential
health  effects.  The  term "acceptable risk" is used  to  denote  the maximum  risk  considered
tolerable by an individual  or  a regulatory agency.  An  acceptable risk level has not  been
strictly  determined  by  EPA.    Although  acceptable  risk  levels  must  be  defined  on  a
case-specific  basis,  past regulatory decisions  that   apply   to  the  U.S. population   have
generally  set  allowable  levels  for  environmental risks  on  the  order  of  10"5 to  10"6
(Travis et al. 1987).
SUMMARY OF ASSUMPTIONS

     Assumptions  underlying  the  risk  assessment  model  and  estimates of  model  variables
should be  summarized  in  a concise  format (see  Table 7 for summary  of some assumptions
and  numerical  estimates   used in  the  approach  presented  in  this  manual).   Specific
assumptions adopted on a case-by-case basis should be summarized in a similar fashion.

     Other assumptions,  such  as  general approaches  or  assumptions  underlying  models
that  are  commonly  used  to   estimate risk,  can  be  summarized  in  the  text  of  a  risk
assessment document.   Some additional  assumptions  involved  in applying  the risk assessment
approach described in this  manual include the following:

     •     Adverse  effects in  experimental animals are indicative of  adverse effects
           in  humans  (e.g., lifetime incidence  of  cancer  in humans  is  the  same as
           that  in animals receiving an equivalent dose  in  units  of mg per  surface
           area)

     •     Dose-response  models can   be  extrapolated  beyond the range of  experi-
           mental  observations  to  yield  plausible-upper-bound  estimates of  risk at
           low doses

     •     A threshold dose does not exist for carcinogenesis

     •     A   threshold  dose  (e.g.,  No-Observed-Adverse-Effect-Level)  exists  for
           noncarcinogenic effects


                                               58

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                          TABLE  7.  SUMMARY OF ASSUMPTIONS  AND NUMERICAL
                            ESTIMATES  USED IN RISK ASSESSMENT APPROACH
         Parameter
    Assumptions/Estimates
      Reference
Exposure Assessment-

Contaminant concentrations
  in tissues of indicator
  species

  Average  consumption rate*
  Gastrointestinal absorption
     coefficient
  Exposure duration

  Human body weight

Risk Characterization:

  Carcinogenic risk model



  Carcinogenic potency
  Noncarcinogenic risk
No effect of cooking
6.5 g/day
20 g/day
165 g/day

1.0
Assumes efficiency of absorp-
tion of contaminants is same
for humans and bioassay animals

70 yr

70 kg (« avg. adult male)
Linearized Multistage
At risks less than 10"2:
Risk * Exposure x Potency

Potency factors are based on
low-dose extrapolation from
animal bioassay data

Upper bound of 95 percent
confidence interval on potency
is used

RfDs for noncarcinogens
compared with estimated
exposure
Worst case for parent
compounds.   Net  effect
on risk is uncertain.

Low, moderate, and
high values for U.S.
population  (see text).

U.S. EPA  1980b; 1986a,b
U.S. EPA 1980b; 1986a,b

U.S. EPA I986a,b
U.S. EPA 1980b, 1986a,
1987a
U.S. EPA 1987a
U.S. EPA 1987a
• Estimates of consumption for local population should be used in place of values shown
for U.S. population whenever possible.

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           The  most sensitive animal  species is appropriate to represent  the  response
           of humans

           Cumulative   incidence  of  cancer  increases  in  proportion  to  the  third
           power  of age  (this  assumption  is  used  to  estimate  lifetime  incidence
           when data are available only from less-than-lifetime experiments)

           For  carcinogens,  average doses  are  an  appropriate  measure  of  exposure
           dose, even if dose rates vary over time

           In the  absence of  pharmacokinetic data,  the  effective  (or  target  organ)
           dose is assumed to be proportional to the administered dose

           Risks from multiple exposures in time are additive

           For  each chemical,  the  absorption efficiency of humans  is equal to that
           of the experimental animal

           If available, human data are preferable to animal data for risk estimation

           For   chemical   mixtures,   risks  for  individual chemicals   are  additive.
           However, the total sum  of individual  chemical  risks  is  not  necessarily the
           total  risk associated   with ingestion   of  contaminated  fish  or  shellfish
           because some important toxic compounds may not have been identified and
           quantified.
UNCERTAINTY ANALYSIS

      Uncertainty  analysis  is  an  integral part  of risk assessment.   A  general  discussion
of  uncertainties present  in  the  risk assessment  approach  described  in this  manual  is
presented  in  the  next  section.   The  EPA  guidelines  on  exposure assessment  describe
general  approaches   for  characterizing   uncertainty  (U.S.  EPA   1986b).    Methods   for
uncertainty  analysis  are  discussed  by  Cox  and  Baybutt  (1981),  Morgan  (1984),  and
Whitmore  (1985).   A  detailed  discussion  of  procedures  is  beyond  the  scope  of   the
present  effort.  General  approaches  to uncertainty  analysis  will  be   described  briefly
after  a discussion of sources  of uncertainty.


Sources of Uncertainty

      Uncertainties  in the  risk assessment  approach presented  in  this  manual arise  from
the following factors:

      1.    Uncertainties  in  the determination of the weight-of-evidence  classification
           for potential carcinogens.

      2.    Uncertainties in estimating Carcinogenic Potency Factors or RfDs,
           resulting from:
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           •     Uncertainties   in   extrapolating   toxicologic   data   obtained  from
                 laboratory animals to humans

           •     Limitations in quality of animal study

           •     Uncertainties in  high-  to  low-dose  extrapolation  of  bioassay  test
                 results,  which   arise from  practical     limitations  of  laboratory
                 experiments and variations in extrapolation models

      3.    Variance of site-specific consumption rates and contaminant concentrations

      4.    Uncertainties  in the  selection of 6.5  g/day, 20  g/day, and 165  g/day as
           assumed consumption rates when  site-specific data are not available

      5.    Uncertainties  in the  efficiency of  assimilation  (or absorption) of  contami-
           nants by  the human gastrointestinal  system  (assumed  to be  the  same as
           assimilation efficiency  of  the experimental  animal  in the  bioassay  used
           to determine a Carcinogenic Potency Factor or RfD)

      6.    Variation of exposure factors among individuals, such as:

           •     Variation in fishery species composition of the diet among  individuals

           •     Variation  in food  preparation   methods  and  associated changes in
                 chemical composition and concentrations due to cooking.

      Variance in  estimates of  carcinogenic potency  or RfDs (#1 above)  account for one
major uncertainty  component in most risk  assessments.   Chemical  potencies  are  estimated
only  on an  order-of-magnitude basis, whereas  analytical  chemistry of tissues is  relatively
precise (on  the  order of  ±20  percent).   The  choice of a  low-dose extrapolation  model
greatly influences  estimates of the Carcinogenic Potency Factor  and  calculated risks.  This
uncertainty contributed  by  the model  is   substantial  when predicting  risks  below  J0~2.
For example, the plausible-upper limit to lifetime cancer  risk associated with 50 ug/L tetra-
chloroethene  in  drinking water  ranges from  about 10"6 for the  probit  model to 10"2 for
the Weibull model (Cothern  et al.  1986).  Model uncertainty  is important when considering
absolute risk estimates  (e.g., Cothern et  al. 1986),  but less  important  for  relative  risk
comparisons.

      Uncertainty  analysis   conducted  by   previous  researchers  illustrates  the  variability
of  risk  estimates  and  potency  factors  for  a  given  extrapolation model.    For  example,
the coefficient  of variation for the  mean  value  of  potency generally  ranged from 2  to
105  percent for each  drinking  water contaminant studied by  Crouch et al.  (1983).  This
uncertainty arose  mainly  from  error associated   with  experimental  bioassay data  for  a
single animal  species.   Among  bioassay  species,  the potency  of  a  given  chemical may
vary  only  slightly or  up to  approximately 1,000-fold, depending  on  the  chemical   in
question (Clayson et  al.  1983).  Thus, the  uncertainty associated  with extrapolating potency
factors from laboratory animals  to  humans  may be  much greater  than the uncertainty
associated  with  animal  bioassay  techniques.  By  comparison,  the  range  of  potencies
among  carcinogens  covers  7-9  orders  of  magnitude  (Clayson  et   al. 1983; U.S.  EPA
1985a).  Relative  risk comparisons  among  chemicals  can be made  more confidently when
the range  of potency factors is  broad.   Note  that  such comparisons should also  include
consideration  of  the  qualitative  uncertainty  (e.g., weight  of  evidence) in  assessing the

                                              60

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specific  health  effects  of  chemicals,  including  mode  of  action,  latency  period,   and
target organs.

     In  conclusion,  uncertainty  ranges  (e.g.,   95  percent  confidence  intervals)   around
estimates  of  mean risk may  typically  span  at least several orders  of magnitude.   The
approach  taken  by U.S. EPA  (I980b,  1985a, 1986a)  and followed  herein is to estimate a
plausible-upper limit  to risk.  In this  way, it is unlikely that  risk will  be  underestimated
substantially.   Moreover, the  plausible-upper-limit  estimate  serves as  a consistent  basis
for  relative  risk  comparisons.     However,  the  effects  of   compounding   conservative
assumptions should be evaluated to provide perspective on risk assessment results.


Approaches to Uncertainty Analysis

     Analysis  of  uncertainty  in  a  risk  assessment  should address both quantitative  and
qualitative   uncertainty.   Quantitative  uncertainty  analysis  deals primarily  with  variation
in  numerical estimates  of  exposure  and  risk  that  results  from  changing  the  values of
variables in mathematical models used to calculate the estimates  (e.g., low-dose extrapolation
models).     Characterization   of variability  in chemical   measurements,  food   consumption
rates,  and   Carcinogenic Potency  Factors (or  RfDs)  and  its effect  on  estimates  of
exposure  and  risk is  an  example  of  quantitative  uncertainty analysis.    A  qualitative
uncertainty  analysis  includes  primarily  a  summary  of  limitations of  the   data  and  the
weight  of  evidence  for toxic effects  of  concern.    A discussion of  qualitative  uncer-
tainties should   present  information  from IRIS on  the level of confidence that  EPA
places  in each Carcinogenic Potency Factor and RfD.

     General approaches to  treatment  of  uncertainty  in  variables used in  risk  analysis
models include the following (Morgan 1984):

     •    Perform analysis  using   single-value-best-estimates   for model   variables
           without uncertainty analysis

     •    Perform single-value-best-estimate analysis,   with  sensitivity calculations
           and appropriate discussion of uncertainty

     •    Estimate some measure  of  uncertainty  (e.g.,  standard deviation)  for each
           model variable and use  error  propagation  methods to estimate uncertainty
           of final exposure or risk value

     •    Characterize  subjectively  the   probability  distribution  of   each  model
           variable and propagate error through stochastic  simulation

     •    Characterize  important   model  variables  using  a  parametric  model  and
           perform risk analysis using various plausible values of each of the variables

     •    Determine  upper  and lower  bounds on  model variables  to  yield  order-of-
           magnitude  estimates and range of possible answers.

Morgan (1984)  refers to the  first  two  approaches as "single-value-best-estimate  analysis,"
to the second  two  as "probabilistic analysis,"  and to  the  final two  as  "parametric/bounding
analysis."    The  analytical  strategies listed  above  are in roughly  descending  order, based
on  the amount  of uncertainty  in  the  model  variables.   Single-value-best-estimate  analysis

                                               61

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 is  appropriate  when  model  variables  are  precisely  known.   Bounding  analysis is  most
 appropriate  when  values  of  model  variables  are  not well-known.   The  techniques listed
 above do  not address  model  uncertainty,  which must be handled by exploratory examina-
 tion of outcomes based on alternative  model equations.

      The  choice of  a method  for  uncertainty analysis  will  depend on  the amount  and
 quality of  exposure data  and  on the  study  objectives.   Quantitative  uncertainty  analysis
 is  applied  mainly  to exposure  variables,  such  as  contaminant  concentration  in   fishery
 species and  consumption  rate.   Following  U.S. EPA (1980b,  I984a,   1985a),  an  upper-
 bound  estimate  of  the Carcinogenic  Potency  Factor is  used  in  carcinogenic  risk calcula-
 tions.   Substitution  of the mean estimate  or the lower bound  of  the  95 percent  confidence
 interval  for the potency  factor in  the risk calculations  is  generally not  done  because of
 the instability of these estimates (U.S. EPA  I980b, 1986a).

      The  U.S.  EPA  (J986b)  guidelines  on  exposure   assessment  and  Whitmore  (1985)
 summarize  the  primary  methods for  characterizing  uncertainty  in  exposure estimates in
 relation  to  attributes  of  the  exposed  population and the exposure  data.   In many cases,
 data  will be  sufficient only  to  use  parametric/bounding analysis, as described  above.   In
 any case, a  discussion of qualitative uncertainties  in the analysis should always  accompany
 presentation   of  risk   assessment  results.    For  example,  limitations  of  data  related to
 inadequate  survey  design  or  insensitive analytical  chemistry  methods should be  described.
 The extent of  chemical   data  for geographic  locations of  interest should be summarized.
 Insufficient  information   on  characteristics  of  the exposed   population should   be  noted.
 The  level  of  confidence  in  data used to develop  RfDs,  Carcinogenic  Potency  Factors,
 and weight-of-evidence classifications based on IRIS  Chemical Files should be indicated.


 SUPPLEMENTARY INFORMATION

      Additional  information to support risk assessment  of contaminated fish  and shellfish
 consumption may include:

      •    Comparisons of  tissue  concentrations of contaminants  with FDA  action
           (or tolerance) levels

      •    Statistical    comparisons   of  mean  contaminant  concentrations  among
           fishery species and  among  locations

      •    Statistical   comparisons  of  mean  contaminant  concentrations  in  fishery
           species with those in other foods.

 FDA  limits  on  contaminants  in  fishery products  are shown  in  Appendix  I.   Limitations
 to  use  of  these  values  for  assessing  health  risk  were  discussed  earlier (see  above.
 Overview  of Risk  Assessment).   For comparison,  legal  limits  on fishery  contaminants
established by other countries are also provided  in Appendix I.

      Some  resource  management agencies  have  developed  advisories based  simply  on
comparisons  between  contaminant concentrations in  fishery  species  and  those  in  corres-
 ponding species  from  reference  or  control  areas.    For example, the  Northeast Shellfish
Sanitation  Commission has  established  "alert  levels"   for   metals  in   shellfish   as  the
concentration equal  to one  standard  deviation  above  the  mean  background  (reference)
                                               62

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concentration.   These alert  levels  are  not  based on  health effects,  but assume  that  the
level of concern is related to an elevation above average background conditions.
                                                63

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Washington, DC.

U.S. Environmental  Protection  Agency and U.S.  Food and Drug Administration.   1987.
Contaminants in  fish:  The  regulation and  control of residues  for  human safety.   Draft
Report.    Prepared  by U.S.  Environmental Protection Agency  Risk Assessment  Council
Subcommittee on  Fish Residue Issues,  Washington, DC  and  U.S.  Food  and  Drug  Ad-
ministration,  Office of Toxicological Studies, Washington, DC.

U.S. Fish and  Wildlife Service.  1986.  Type  B  technical information  document  recom-
mendations on  use  of habitat  evaluation  procedures  and  habitat suitability index models
for CERCLA applications. Draft Report.  U.S. Fish and Wildlife Service, Habitat Evaluation
Procedures Work Group, Fort Collins, CO.  45 pp.
                                             75

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U.S.  Food  and  Drug  Administration.    J978.    Pesticides  analytical manual.    Methods
which detect  multiple  residues:   foods and  feeds.   U.S.  Food  and  Drug Administration,
Washington, DC.

U.S. Food  and Drug  Administration.  1982.   Levels  for poisonous or deleterious substances
in human  food and  animal feed.   U.S. Food  and Drug  Administration,  Washington,  DC.
13 pp.

U.S. Food  and  Drug  Administration.  1984.   Polychlorinated  biphenyls  (PCBs)  in  fish
and  shellfish;  reduction of tolerances; final decision.   U.S. Food and  Drug Administration,
Rockville, MD.  Federal Register, Vol. 49,  No. 100.  pp. 21514-21520.

U.S.  Food  and  Drug  Administration.    1986.   Pesticides  and  industrial  chemicals  in
domestic foods  (FY  86).    Compliance Program  Guidance  Manual.   Programs  7304.004,
7304.004c,  7304.010.  U.S. Food and Drug Administration, Washington, DC.

U.S. Office of  Science  and  Technology  Policy.  1985.   Chemical carcinogens;  a  review
of the science  and its  associated principles.  Federal Register, Vol. 50. pp.  10372-10442.

U.S. Office of Technology  Assessment.    1979.   Environmental   contaminants  in  food.
U.S. Office of Technology  Assessment, Washington, DC.  229 pp.

Vaessen, H.A.M.G.,  P.L.   Schuller,  A.A. Jekel,  and  A.A.M.M.  Wibers.    1984.   Polycyclic
aromatic hydrocarbons  in  selected   foods:   analysis  and  occurrence.   Toxicol.  Environ.
Chem. 7:297-324.

Versar,  Inc.   1985.   Assessment of  human health risk from  ingesting fish and crab from
Commencement  Bay.   EPA 910/9-85-129.   Prepared  for  U.S. Environmental  Protection
Agency, Office of Solid Waste and Emergency  Response.  Versar, Inc., Springfield, VA.

Whitmore,  R.W.    1985.    Methodology  for  characterization  of  uncertainty  in  exposure
assessments.  Final  Report.  OHEA-E-160.  Office of Health and Environmental Assessment,
Washington, DC.  44 pp. + appendices.

Whittemore, A.S.   1983.    Facts  and values in  risk  analysis  for  environmental toxicants.
Risk Analysis  3:23-33.

Wilson,  R., and  E.A.C.  Crouch.    1987.    Risk assessment  and  comparisons:    an intro-
duction.  Science 236:267-270.
                                              76

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                             APPENDIX A




EPA OFFICE OF WATER CONTACTS ON RISK ASSESSMENT FOR FISH CONSUMPTION

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                                  APPENDIX A

EPA OFFICE OF WATER CONTACTS ON RISK ASSESSMENT FOR FISH CONSUMPTION


        Name            Organization            Phone          Subject Area

   Kim Devonaid      Office of Marine and   (202) 475-7114   EPA Coordination on
                     Estuarine Protection                    Fish Health Risk
                                                          Assessment

   Frank Gostomski   Office of Water        (202) 475-7321   Derivation of Refer-
                     Regulations and                        ence Doses for
                     Standards                             Toxic Chemicals

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                 APPENDIX B






INTEGRATED RISK INFORMATION SYSTEM (IRIS)




          (excerpt from U.S. EPA 1987a)

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                                 INTRODUCTION TO IRIS
 OVERVIEW
 IRIS is a computer-housed, electronically communicated catalogue of Agency risk assessment and risk
 management information for chemical substances. This system is designed especially for federal,
 state, and local environmental health agencies as a source of the latest information about Agency
 health assessments and regulatory decisions for specific chemicals.

 The development of IRIS is a response to repeated requests for Agency risk assessment information
 to deal with various environmental issues and a response to the need for consistency and quality in
 EPA risk assessment and risk management decisions. IRIS is intended to introduce the user to Agency
 information which may be useful for building the database necessary to make a risk assessment.

 IRIS is not a primary toxicologic data base or a conclusive risk resource; rather, it is an introduction to
 EPA's risk information, and should be used  with an understanding of its capabilities as well as its
 limitations and constraints (see  background documents  in  Service Code 4).  Supportive
 documentation included in the system provides instruction and explanation for the risk information
 presented. The information contained in IRIS is intended for users without extensive training in
 toxicology, but with some knowledge of health science.

 The risk assessment information contained in IRIS, except as specifically noted, has been  reviewed
 and agreed upon by intra-agency review groups, representing an Agency consensus. An intra-agency
 work group has been responsible for the development of IRIS.

 As  intra-agency review groups  continue to review and verify  risk assessment values, additional
 chemicals and data components will be added to IRIS. Although IRIS is available in hardcopy, it is also
 available through  Dialcom, Inc.'s Electronic Mail,  the computer-based electronic communications
 system to which the EPA subscribes. Designed as an electronic loose-leaf notebook, IRIS provides
 users with the ability to access, copy, and print information from the data base. IRIS harcfcopy, which
 will be available in the future through the National Technical  Information Service (NTIS), is provided
 initially to help users get started. This material can then be expanded and updated by users through
 electronic retrieval of new and revised data.

 SYSTEM STRUCTURE

 The information contained within IRIS is divided into two major  components: the chemical files,
 which form the heart of the system, and the supportive documentation, which provides instruction
 and explanation in support of the system and the chemical files. This  information is distributed
 among six Service Codes, with the chemical files (the functional files in  IRIS) contained in one Service
 Code and the supporting documentation contained in the remaining five. The Service Codes and
their functions are as follows:

Service Code 1     Chemical Files: This is the heart of the system. It is within this file that the actual
                  chemical-specific data have been compiled. A detailed presentation of the
                  content and format of this Service Code will be provided later in this Introduction
                  and in the Chemical Fife Structure description in Service Code 4.

Service Code 2     List of Chemicals on IRIS: A simple alphabetical and Chemical Abstract  System
                  (CAS) number listing of all the chemicals contained in IRIS.

                  Chemical File Update Information:  The chemical files which have been recently
                  updated are listed here. Chemical name, CAS No. and date of revision are given.

Service Code 3     Chemical File Revision History:  This Service  Code contains a running record of
                 specific revisions to each chemical file. The information is more specific than that
                 found in Service Code 2, which is just a list of updated fifes. The specific file
                 sections that have been changed or modified are given and the type of change is
                 indicated (e.g., "Oral  RfD: UF text modified", "Risk  Estimates for Carcinogens:
                 slope factor corrected", "Risk Management Section added", etc.). The date of the
                 change is also given.

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Service Code 4    Introduction to IRIS (this document): a brief overview of IRIS.

                 Chemical File Structure: General background information is provided on each of
                 the data elements contained in the chemical files. This section is intended to help
                 the user understand the information contained in the chemical files. In addition.
                 there is some discussion of the general limitations, restrictions, and qualifications
                 placed on the EPA data so  as to minimize misinterpretation of the data
                 presented.

                 Background Documents (Appendices):  Concept papers are  provided  for the
                 categories of information  contained  in the  chemical  files (oral RfD,
                 carcinogenicity assessment, risk management actions, and supplementary data).
                 As background documents are prepared for other information categories, such as
                 inhalation RfDs or Drinking Water Health Advisories, they will be added to the
                 system.

                 EPA  Chemical Profile  Database References: List of references cited  in the
                 Supplementary Data section of the chemical files is provided at the end of the
                 background document for that section.
Service Code 5


Service Code 6
Glossary: A glossary of terms and abbreviations used in the chemical files and
supportive documentation is provided for user reference.

User's Guide: An operations manual is provided which describes how to use the
system and lists commands, procedures, helpful hints, and a series of examples for
illustration.

Case Study: A case study is included to provide an example of a situation to which
IRIS can be applied and how the information it contains might be used.
              1. Chemical files.
                2. List of chemicals in IRIS.
                 3. Revision information.
                   4. Background information.
                    5. Glossary.
                      6. User's guide and case study.
                                Service Codes in IRIS

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CHEMICAL FILE FORMAT

The chemical files are intended to assist the user in developing risk assessments which can be used in
making management decisions for specific situations. For reference, agency risk management
information is also included. One is cautioned, however, that the EPA risk management data have
been developed for conditions and with constraints which may have little applicability to a given
user's specific situation.

Each chemical  file begins with a short introductory paragraph followed by a status table indicating
the availability of various components of the chemical file. The information contained within the
chemical file includes risk assessment and risk management information. The specific chemical file
content is outlined below:

                            IRIS CHEMICAL FILE STRUCTURE

INTRODUCTION AND STATUS

        I.  CHRONIC SYSTEMIC TOXICITY (NON-CARCINOGENIC HEALTH EFFECTS)

           A.  REFERENCE DOSE (RfD) FOR ORAL EXPOSURE

               1. REFERENCE DOSE SUMMARY TABLE
               2. PRINCIPAL AND SUPPORTING STUDIES
               3. UNCERTAINTY AND MODIFYING FACTORS
               4. ADDITIONAL COMMENTS
               5. CONFIDENCE IN THE RfD
               6. DOCUMENTATION AND REVIEW
               7. U.S. EPA CONTACTS

           B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE

               (same format as for oral exposure)

       II.  RISK ESTIMATES FOR CARCINOGENS

           A.  U.S. EPA CLASSIFICATION AND BASIS

               1. HUMAN DATA
               2. ANIMAL DATA
               3. SUPPORTING DATA

           B.   ORAL QUANTITATIVE ESTIMATE
               1. UNIT RISK SUMMARY TABLE
               2. DOSE RESPONSE DATA
               3. ADDITIONAL COMMENTS
               4. STATEMENT OF CONFIDENCE

           C.   INHALATION QUANTITATIVE ESTIMATE

               1. UNIT RISK SUMMARY TABLE
               2. DOSE RESPONSE DATA
               3. ADDITIONAL COMMENTS
               4. STATEMENT OF CONFIDENCE

           D.   DOCUMENTATION AND REVIEW

               1. REFERENCES
               2. REVIEW
               3. U.S. EPA CONTACTS

      III.   DRINKING WATER HEALTH ADVISORIES
           (format in preparation)

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       IV.   RISK MANAGEMENT SUMMARIES

            A. RISK MANAGEMENT ACTIONS

            B. RISK MANAGEMENT RATIONALE

       V.   SUPPLEMENTARY DATA

            A. ACUTE HEALTH HAZARD INFORMATION

            B. PHYSICAL-CHEMICAL PROPERTIES

            SYNONYMS

Each section consists of a data and rationale summary of two or three pages in length. In addition,
EPA contacts who  are familiar with the chemical are provided in each section (except  for the
Supplementary Information section).

Unavailability of data for a section will be indicated, and, if known, other information pertaining to
the status of the data will be provided. A more detailed description  of each of these sections is
provided in the Chemical File Structure document following this Introduction.

ELECTRONIC REPRESENTATION OF SPECIAL CHARACTERS

The use of a computerized telecommunication system for IRIS imposes limits on the number and
types  of  nonalphanumeric characters that can be represented. Special characters such as degree
symbols or Greek letters, and print codes such as superscripts and subscripts cannot be reproduced on
most display terminals. Therefore, very small numbers are given in scientific notation using the "E"
format. That is, a number such as 0.0006 is expressed as 6E-4, which is equivalent to saying "6 times
10 to the power of-4." Large numbers are given in "E" format in some instances, for consistency (for
example, 2E2 for the number, 200). Some other substitutions for notations generally  represented by
superscripts or subscripts are: "cu. m" for cubic meter, "**"  for exponentiation in formulas (for
example, "Y =  X"2" represents "Y equals X squared"), and Ca(CN)2  for the chemical formula of
calcium cyanide (chemical formula subscripts are subscripted  one full line in other instances). Upper
case "L" is occasionally used as the abbreviation for liter in those cases where the lower case "I" may
be misinterpreted as the number, one.

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                           IRIS CHEMICAL FILE STRUCTURE
PREFACE

The user is directed to Service Code 6 for instructions on how to call up information on specific
chemicals. The discussion below supplements the introduction under Service Code 4 by describing in
detail the information displayed in each of the chemical-specific files. The Appendices are
background documents which provide more detailed information on risk assessments and risk
management concepts and terms.

When one calls up a chemical, sections of information are displayed  in the following order:
INTRODUCTION  & STATUS, CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS,
RISK ESTIMATES FOR CARCINOGENS, DRINKING WATER HEALTH ADVISORIES, RISK MANAGEMENT
SUMMARIES, SUPPLEMENTARY DATA, and SYNONYMS. Each numbered section (all sections except
the Introduction and Synonyms) begin with a heading with the following information:

    Chemical: The chemical name of the agent is given, with the common name in parentheses
             where appropriate.

    CAS No.:   The Chemical Abstract Service number unique to the compound.

    Preparation date:   The date of the most recent revision of the summary sheet.

The subsections and data entries found in each of the sections are discussed below.

  INTRODUCTION AND STATUS

  The chemical  name and Chemical  Abstracts Service  (CAS) number which uniquely identifies this
  substance is given, along with the latest revision date for the  chemical file. An introductory
  statement is included in each file, followed by a status table indicating the  availability of each
  section. A status of  "review pending" means that  a chemical  is currently under review, or is
  scheduled for review by an EPA work group.

  /. CHRONIC SYSTEMIC TOXICITY: NON-CARCINOGENIC HEALTH EFFECTS

  Risk assessors are often faced with  the task of interpreting the significance of  long-term exposure
  to chemicals which might produce toxic effects other than cancer. These effects  are sometimes
  referred to as the "systemic toxicity" of the compound. Traditionally, these effects have been
  assessed by identifying the lowest  No Observed Effect Level (NOEL) and reducing this amount by
  some factor (Safety Factor or Uncertainty Factor) to estimate a level which is judged to be without
  significant toxicologic concern to humans.

  The CHRONIC SYSTEMIC TOXICITY section contains chemical-specific information couched in terms
  of a Reference Dose (RfD), a concept which is discussed in greater detail in Appendix A. The RfD is
  related to a formerly used notion of "acceptable daily intake (ADI)" but has been tailored to the
  risk assessment/risk management approach used at EPA.

    A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE

     Chemical name, CAS No., and preparation date are given.

       1. REFERENCE DOSE SUMMARY TABLE

       This table summarizes the data used in the derivation of the reference dose.

         Critical Effect

         This first column lists the critical effect, the species and type of study, and the reference.

         Experimental Doses

         The second column is a summary of the information on the highest level at which no
         adverse effects were found (i.e.. the No Observed  Adverse Effect Level [NOAEL]) and/or

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   the lowest level tested at which adverse effects were found (i.e., the Lowest Observed
   Adverse Effect Level [LOAEL]). The dose levels are usually given in the units presented in
   the original study and in units of milligrams per kilogram body weight per day (mg/kg/day
   or mg/kg-day).

   UF

   The  Uncertainty Factor which  contributes as a divisor to the NOAEL (or LOAEL) in
   calculating the Reference Dose is given. In most instances, these uncertainty factors are
   standardized, based on the particular data set available. See the paper on the  Reference
   Dose in Appendix A for a more complete description.

   MF

   The Modifying Factor  which also contributes as a divisor to the NOAEL in calculating the
   Reference Dose is given, in  most cases, this factor is 1; however, in certain instances, the
   review group uses its collective professional judgment to adjust the RfD through the use
   of a Modifying Factor. In such cases, explanations are provided in the text following the
   table.

   RfD

   The RfD is an estimate (uncertainty spanning perhaps an order of magnitude)  of a daily
   exposure to the human population (including sensitive subgroups)  that is likely to be
   without an appreciable risk of deleterious effects during a liftime. The RfD is expressed in
   units of milligrams per kilogram body weight per day (mg/kg/day  or mg/kg-day).  See
   Appendix A for a full discussion of the concept and its use in risk  assessment and  risk
   management.

   Doie Conversion Factors And Assumptions

   The factors used to convert the dose to mg/kg-day are listed, as well as any assumptions
   made. These factors include food and water consumption, and, in some cases, inhalation-
   to-oral conversion factors.

2. PRINCIPAL AND SUPPORTING STUDIES

An elaboration of the material in  the  summary table immediately above is presented,
providing descriptions of the critical study and other germane studies.

3. UNCERTAINTY AND MODIFYING FACTORS

An explicit presentation of the individual Uncertainty  Factors contributing to the overall
Uncertainty Factor is given. The UFs are:

10-fold factor for extrapolation from animal to human (lOa)
10-fold factor for variability in the human population (10h)
10-fold factor for use of a less-than-chronic study (10s)
1 to 10-fold factor for extrapolation from a LOAEL (1 -> I0e)

See Appendix A for a more complete discussion.

An explicit explanation of the selection of any Modifying Factor is also presented.

4. ADDITIONAL COMMENTS

Ancillary information is given which may be of use or interest, e.g., other approaches taken
to establishing an RfD and why EPA prefers its approach.

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     a. CONFIDENCE IN THE RfD

     This entry provides a qualitative estimate, expressed in both summary and narrative form, of
     the  confidence that the EPA review group had in  the  quality of the critical study,  the
     supporting data base, and the RfD. A "Low" designation for the RfD suggests that the value
     is likely to change as new data are generated.

     6. DOCUMENTATION AND REVIEW

     The EPA document(s) in which the RfD (ADI) was originally derived, and the level of review of
     that document, are given. The dates of the RfD work group meetings at which the chemical
     was discussed are also given.

     7. U.S. EPA CONTACTS

     Persons to contact for additional details on  the technical issues associated with the RfD of
     this chemical are listed.

  B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE

  Inhalation RfD methods are under development.

//. RISK ESTIMATES FOR CARCINOGENS

  A. U.S. EPA CLASSIFICATION AND BASIS

  Classification

  The EPA weight-of-evidence classification  of the  agent, as described  in the  Hazard
  Identification section (HA) of appendix B.

     1. HUMAN DATA

     A description of the human evidence leading to the classification. Difficulties in determining
     the final classification are also given where necessary.

     2. ANIMAL DATA

     A description of the experimental animal evidence leading to the classification. Difficulties in
     determining the final classification are given  where necessary.

     3. SUPPORTING DATA

     A description of data fending support to the classification, such as genotoxicity.

  B. ORAL QUANTITATIVE ESTIMATE

  Slope Factor

  The upper-bound incremental lifetime cancer risk estimated to result from a continuous orally
  absorbed dose of 1 mg per kg body weight per day. Since the oral absorption fraction is usually
  assumed to be 100%, the same oral slope factor is used for continuous oral intake.

     1. UNIT RISK SUMMARY TABLE

     Water concentration producing risk levels of E-4, E-5, E-S

     The concentration of the agent (micrograms per liter) in drinking water estimated to  result in
     upper-bound incremental lifetime cancer  risk of E-4, E-5, E-6, if 2 liters of water which is
     contaminated with the agent were ingested per day continuously for a lifetime.

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  Unit Risk

  The upper-bound incremental lifetime cancer risk estimated to result from ingestion of 2
  liters of water per day of drinking water contaminated with the agent at a concentration of
  one microgram per liter.

  Model

  The abbreviation for the dose extrapolation model used to estimate cancer risk at low doses
  from experimental observations at higher doses. M is the multistage procedure, W is Weibull,
  P is probit, LO is logit, OH is one-hit, GM is gamma multi-hit.

  2. DOSE-RESPONSE DATA

  This table shows the animal data set from which the risk parameters were estimated. The
  table shows the species and strain of the animals used, the tumor type or types used for the
  estimate, the dose administered in the experiment, the lifetime tumor incidence observed, a
  code for the literature citation of the report where the data was published, and the route of
  administration used in the experiment. The table is modified when human data are used for
  the estimation of risk parameters.

  3. ADDITIONAL COMMENTS
  An  explanation of the assumptions used in deriving the risk estimate. For each agent the
  following information is presented:

      method of selecting the data set,

      animal-to-human equivalent dose assumption,

      statement of whether the administered animal dose or a pharmaco-kinetically-derived
      effective metabolized dose was used, and

      relevant non-cancer toxicity.

  Other  comments describing the estimation procedure for the  agent are included. A
  statement is also made that the risk estimate should not be used if the water concentration is
  larger than x ug/l and the air concentration is larger than y ug/cu.m. In this statement the
  values of x and y are the concentrations above which the risk exceeds 1.0%.

  4. STATEMENT OF CONFIDENCE
  A high, medium, or low rating based on the factors enumerated in section II of appendix B. A
  description of the main factors leading to this rating is included.

C INHALA TION QUANTITA TIVE ESTIMA TE

The entries in this subsection  are  analogous to those in the Oral Quantitative Estimate
subsection above.

D. DOCUMENTATION REVIEW

  1. REFERENCES
  Literature citations  for the major papers used in the classification of the agent and in
  quantitative estimates.

  2. REVIEW

  Description of the review procedure received  by the EPA evaluation document which is
  summarized by these sheets:

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        Agency CRAVE Work Group Review
        Dates on which the Agency review committee met to review data on the agent.
        Verification Date
        Date on which the Agency review committee agreed that the information is accurate.
     3. U.S. EPA CONTACTS
     The person or persons at EPA who can explain the origin of the items on the summary sheet.
///. DRINKING WATER HEALTH ADVISORIES
Health advisories are still under development.
IV. RISK MANAGEMENT SUMMARIES
INTERPRET A TION OF RISK MANAGEMENT DATA
A cautionary statement is presented concerning the interpretation of the data.
  A. RISK MANAGEMENT ACTIONS
  A table summarizing the risk management actions taken by the U.S. EPA is given. This table
  includes the following categories:
     Risk Management Action
     The type of action (i.e., official name)
     Status
     Current status of this action
     Date
     Date of the action
     Risk Management Value
     The numeric risk management value. Some values are specific for duration of exposure, and
     are so indicated. Values that vary according to a given set of conditions (e.g., site-specific
     values) will not be listed here. Call the EPA Contact for specific information.
     Considers EconlTefh Feasibility
     Indicates whether or not the economical or technical feasibility of the risk management
     action has been considered prior to setting the value.
     Reference
     The document in which the value was published.
  B. RISK MANAGEMENT RATIONALE
  The chemical-specific information underlying each of the risk management actions is described.
  U.S. EPA contacts are also given.

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V. SUPPLEMENTAR Y DA TA

  A. ACUTE HEALTH HAZARD INFORMATION

  In response to concerns raised following the tragic release of toxic substances from a chemical
  plant in Bhopal, India in  1985, EPA has generated a list of chemicals which could conceivably
  pose acute hazards to people living in the neighborhood of production or storage facilities. The
  list includes a range of chemical-specific information which would  be useful in assessing the
  significance of levels determined in the environment.

  B. PHYSICAL-CHEMICAL PROPERTIES

  The chemical and physical properties of the compound are listed and other properties of the
  substance are presented.

  SYNONYMS

  A listing of synonyms for the chemical as extracted from a number of sources is given.

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  100-42-5   Etrrene
62476-59-9   Tackle
 59O2-51-2   Terbacll
   95-94-3   1.2.4,S-Tetrachlorobencene
   79-34-5   1,1,2.2-Tetrachloroethane
  127-18-4   Tetrachloroethrlene
   58-90-2   2.3.4.6-Tetrachlorophenol
  961-11-5   Tetrachlorovlnphos
   78-00-2   Tetraethyl Lead
 1314-32-5   Thalllc O*lde
  563-68-8   TtuUllua Acetate
 6533-73-9   Thallium Carbonate
 7791-12-0   Thalllua Chloride
10102-45-1   Thalllua Nitrate
12039-52-0   Thai HUB Selenlte
 7446-18-6   Thalllua(I) Sulfate
235C4-05-B   Thlophanate-Mthrl
  108-88-3   Toluene
 2303-17-5   Triallate
  615-54-3   1.2.4-Trlbroawbencene
  120-82-1   1.2.4-Trlchlorobencene
   71-55-6   1.1.1-Trlchloroethane
   79-00-5   1.1,2-Trlchloroethane
   79-01-6   TrlchloroethrlwM
   75-69-4   Trlchloroaonof luoroaMthaae
   95-95-4   2.4.5-Trlchlorophenol
   88-OC-2   2.4.6-Trlchloropbeaol
   96-18-4   1.2.3-TrlcMoropropana
   76-13-1   1.1.2-Trlchloro-1.2.2-trlfluoroetbai>e (H-113)
no CAS No.   Trlxllphane
 1314-62-1   Taaadlua Pentorlde
 1929-77-7   Vernaa
50471-44-8   Tlnclocolio
   81-81-2   Warfarin
  557-21-1   Zinc Cyanide
 1314-84-7   Zinc Phosphide
12122-67-7   Zlneb

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Lindane:  page 2 of 7
        I.  CHRONIC SYSTEMIC TOXICITY:   NONCARCINOGENIC HEALTH EFFECTS

INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA

 The Reference Dose (RfD) is based on the assumption that thresholds may exist
 for certain toxic effects such as cellular necrosis,  but may not exist for
 other toxic effects such as carcinogenicity.   The RfD is considered to be the
 level unlikely to cause significant adverse health effects associated with a
 threshold mechanism of action in humans exposed for a lifetime.   RfDs can
 also be derived for the noncarcinogenic health effects of compounds which are
 also carcinogens.  Therefore, it is essential to refer to section II, and
 other sources as well, for risk assessment information pertaining to the
 carcinogenicity of this compound.  Please refer to the Background Document on
 the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.


   A.  REFERENCE DOSE (RfD) FOR ORAL EXPOSURE

Chemical:  Lindane
CAS No.:   58-89-9                                Preparation Date:  04/28/86


1.  REFERENCE DOSE SUMMARY TABLE


 Critical Effect         Experimental Doses  *        UF     MF       RfD


 Liver and kidney        4 ppm diet 0.3 mg/kg       1000      1      3E-4
 toxicity                bw/day (females)                           mg/kg/day
                         (NOAEL)
 Rat, subchronic oral
 bioassay                20 ppm diet 1.55
                         mg/kg bw/day (males)
 RCC (1983)              (LOAEL)


 * Dose Conversion Factors & Assumptions:  none


2.  PRINCIPAL AND SUPPORTING STUDIES

Research and Consulting Co., Ltd.  1983.  Ace. Nos. 250340-250342.
Available from EPA.  Write to FOI, EPA, Washington D.C. 20460.

    Twenty male and 20 female Wistar KFM-Han (outbred) SPF rats/treatment
group were administered 0, 0.2, 0.8, 4, 20 or 100 ppm lindane (99.851) in the
diet.  After 12 weeks, 15 animala/sex/group were aacrificed.  The remaining
rats were fed the control diet for an additional 6 veeks before sacrifice.
No treatment-related effects were noted on mortality, hematology, clinical
chemistry or urinalysis.  Rats receiving 20 and 100 ppm lindane were observed
to have greater-than-control incidence of the following:  liver hypertrophy,
kidney tubular degeneration, hyaline droplets, tubular diatension, inter-
stitial nephritis and basophilic tubules.  Since these effects were mild or
rare in animals receiving 4 ppm, this represents a NOAEL.  The reviewers of
the study calculated the dose to be 0.29 mg/kg/day for males and 0.33
mg/kg/day for females, based on measured food intake.

-------
 Llndane:  page  3 of  7


     In a  2-year feeding study  (Fitzhugh, 1950), 10 Wistar rats/sex/group were
 exposed to  5, 10,  50, 100, AGO, 800 or 1600 ppm lindane.  Slight liver and
 kidney damage and  increased liver weights were noted at the 100 ppm level.
 If a food intake equal to 5% body weight is assumed, a NOAEL of 2.5 tng/kg
 bw/day (50  ppm) can  be determined from this assay.  In a 2-year bioassay
 (Rivett et  al., 1978), four beagle dogs/sex/group were administered 0, 25, 50
 or 100 ppm  lindane in the diet.  Treatment-related effects noted in the
 animals of  the  100 ppm group were increased serum alkaline phosphatase and
 enlarged dark friable livers.  A NOAEL was determined to be 50 ppm (1.6 mg/kg
 bw/day).

    Use of  the  NOAEL derived from the RCC (1983) study is most appropriate, in
 keeping with the practice of utilizing data from the most sensitive species
 (or strain) as  a surrogate for humans when human data are lacking.


 3. UNCERTAINTY AND MODIFYING FACTORS

 UF - 1000.  A factor of 10 each was employed for use of a subchronic vs. a
 lifetime assay, to account for interspecies variation and to protect
 sensitive human subpopulations.

 MF - 1


 4. ADDITIONAL COMMENTS

    Data on reproductive effects of lindane are inconclusive.  Most reports
 Indicate that hexachlorocyclohexane iaomers are nonteratogenic.


 5. CONFIDENCE IN THE RfD

    Study:  Medium              Data Base:  Medium              RfD:  Medium

    The RCC (1983) study used an adequate number of animals and measured mul-
 tiple end points.  Since there are other reported chronic and subchronic
 studies, confidence  in the study, data base and RfD is considered medium.


 6. DOCUMENTATION AND REVIEW

 U.S. EPA.    1985.  Drinking Water Criteria Document for Lindane.   Office of
 Drinking Water, Washington, DC.

 The RfD in  the  Drinking Water Criteria Document has been extensively reviewed
 by U.S. EPA scientists and selected outside experts.

Agency RfD Work Croup Review:  01/22/86

Verification Date:   01/22/86


7. U.S. EPA CONTACTS

Primary:     M.L. Dourson           FTS/684-7544 or 513/569-7544
            Office of Research and Development

Secondary:  C.T. DeRosa            FTS/684-7534 or 513/569-7534
            Office of Research and Development

-------
Lindane :  page 4 of 7
  B.  REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE

Chemical:  Lindane
CAS No.:    58-89-9
 Information is not available at this time.
Chemical:
CAS No.:
                    II.  RISK ESTIMATES FOR CARCINOGENS
Lindane
58-89-9
     This chemical is among those substances evaluated by the U.S.  EPA for
 evidence of human carcinogenic potential.   This does not imply that this
 chemical is necessarily a carcinogen.   The evaluation for this chemical is
 under review by an inter-office Agency work group.   A risk assessment summary
 will be included on IRIS when the review has been completed.
                  III.  DRINKING WATER HEALTH ADVISORIES
Chemical:
CAS No.:
Lindane
58-89-9
 Information is not available at this time.
                      IV.  RISK MANAGEMENT SUMMARIES
Chemical :
CAS No.:
Lindane
58-89-9
Preparation Date:  09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA

 EPA risk assessments may be continuously updated as new data are published
 and as assessment methodologies evolve.   Risk management (RM) decisions are
 frequently not updated at the same time.  Carefully read the dates for the
 risk management actions (in this section) and the verification dates for the
 risk assessments (in sections I & II), as this may explain apparent inconsis-
 tencies.  Also note that some risk management decisions consider- factors not
 related to health risk, such as technical or economic feasibility.  Such
 considerations are indicated in the table below (Considers Econ/Tech
 Feasibility).  Please direct any questions you may have concerning the use of
 risk assessment information in making a risk management decision to the
 contact listed in Part B of this section (Risk Management Rationale).  Users
 are strongly urged to read the background information on each RM action in
 Appendix E in Service Code 4.

-------
INTEGRATED RISK INFORMATION SYSTEM:   Chemical  Files


Lindane; CAS No. 58-89-9 (Revised 11/16/1986)


USE AND INTERPRETATION OF THE DATA IN IRIS

      Health risk assessment information on chemicals  is  included in IRIS  only
 after a comprehensive review of chronic toxiclty data by work groups
 composed of U.S. EPA scientists from several  Agency Program Offices.  The
 summaries presented in Sections I and II represent  *  consensus reached in
 those reviews.  The conceptual bases of these risk  assessments are described
 in Appendices A & B in Service Code 4.   The other sections  are supplementary
 information which may be useful in particular risk  management situations, but
 have not yet undergone comprehensive U.S. EPA review.  The  risk management
 numbers (Section V) may not be based on the most current risk assessment, or
 may be based on a current, but unreviewed, risk assessment, and may take  into
 account factors other than health effects (e.g., treatment  technology).   When
 considering the use of risk management numbers for  a  particular situation,
 note the date of their development, the date  of the most recent risk
 assessment, and whether technological factors were  considered.  For a more
 detailed description of procedures used in these assessments and the
 development of risk management numbers, see Appendix  E in Service Code A.

STATUS OF DATA FOR  Lindane

  I.   Chronic Systemic Toxicity:  Noncarcinogenic Health Effects

      A.  Oral RfD:                               available

      B.  Inhalation RfD:                         none

  II.  Risk Estimates for Carcinogens:            review pending

  III.  Drinking Water Health Advisories:          none

  IV.  Risk Management Summaries:                 available

  V.   Supplementary Data:                         available

-------
LIndane:  page 5 of 7
  A.  RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Statutory
1980
Risk
Management
Value
1 Ib
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
 a. Human Health

 b. Aquatic Toxicity
   1) Freshwater
              18.6  ng/1        no
   2) Marine
Pesticide Active
Ingredient:
 a. Registration
    Standard

 b. Special
    Review
Final       Acute             no
1980           2.0 ug/1
            Chronic
             0.080 ug/1
Final       Acute             no
1980          0.16 ug/1
            Chronic
              none
Current
1985
various
Termination  P.D.  1
of RPAR
1983
                no
                no
  B. RISK MANAGEMENT RATIONALE
RQ
                             45 FR 79318
                             11/28/80

                             45 FR 79318
                             11/28/80
                             ibid.
Reg. Std.
Sept. 1985

42 FR 9816
02/18/77
P.D.

P.D.

2/3

4

yes

yes

45 FR 45362
07/03/80
48 FR 48512
09/30/83
     The statutory RQ of 1 pound established pursuant to CERCLA Section
 102(b) is retained until the assessment of potential carcinogenicity is
 complete.
   Contact:  Office of Emergency and Remedial Response
             202\382-2180 or FTS\382-2180

WQC
   Contact:  Office of Water Regulations and Standards
             202-382-5400 or FTS-382-5400

 a. Human health: The WQC of 18.6 ng/1 represents a cancer risk level of
 1E-6 based on consumption of contaminated organisms and water.  A WQC of
 62.5 ng/1 has been established based on consumtion of contaminated aquatic
 organisms alone.

 b. Aquatic toxicity:  Water quality criteria for the protection of aquatic
 life are derived from a minimum data base of acute and chronic tests on a

-------
 Llndane:  page 6 of 7


 variety of aquatic organisms.  The data are assumed to be statistically
 representative and are used to calculate concentrations which will not have
 significant short or long term effects on 95% of the organisms exposed.
 Recent criteria (1985 and later) contain duration and frequency stipulations:
 the acute criteria maximum concentration is a 1-hour average and the chronic
 criteria continuous concentration is a 4-day average which are not to be
 exceeded more than once every three years, on the average (see Stephen et al.
 1985).  Earlier criteria (1980-1984) contained instantaneous acute and
 24-hour average chronic concentrations which were not to be exceeded. (FR 45:
 79318: November 28, 1980).  The freshwater chronic WQC is a 24-hour average.

 Pesticide Active Ingredient
 a. Regulation Standard:  Lindane Pesticide Registration Standard.
 September 1985.  Registration Support and Emergency Response Branch.
 Office of Pesticide Programs.
   Contact:  Office of Pesticides Programs
             202/557-7760 or FTS/557-7760

 b. Special Review:  Negotiated settlements have been made for Lindane in dog
 dips  [49 FR 26282 (06/27/84)] and in smoke bombs [50 FR 5424 (02/08/85)].
   Contact:  Office of Pesticides Programs, Special Review Branch
             202/557-7420 or FTS/557-7420
                          V. SUPPLEMENTARY DATA

Chemical:  Lindane
CAS No.:   58-89-9                                Preparation Date:  11/07/86


              USE AND INTERPRETATION OF SUPPLEMENTARY DATA

 The information contained in this section (subsections A and B) has been
 extracted from the EPA Chemical Profiles Database, which has been compiled
 from a number of secondary sources and has not undergone formal Agency
 review.  The complete reference listings for the citations below are provided
 in Service Code 4.  The user is urged to read the background document for
 this section (Appendix E in Service Code 4) for further information on the
 sources and limitations of the data presented here.


A.  ACUTE HEALTH HAZARD INFORMATION

    Lindane is a stimulant of the nervous system, causing violent convulsions
 that are rapid in onset and generally followed by death or recovery with 24
 hours (Hayes, 1982, p.  218).  The probable human oral lethal dose is 50-500
 
-------
Lindane:   page 7 of 7


 reported in children.   Coma,  respiratory failure and death can result.
 Exposure to vapors of this compound,  or its thermal decomposition products,
 may lead to headache,  nausea, vomiting, and irritation of the eyes,  nose,  and
 throat (Gosselin, 1984, pp.  III-240,  241).


B.  PHYSICAL-CHEMICAL PROPERTIES

    Chemical Formula:  C H Cl
                        666
    Molecular Weight:  290.83
    Boiling Point:  614F, 323.4C;  Decomposes
    Specific Gravity (H20-1):  1.9
    Vapor Pressure (mmHg):  9.4 x 10-6 at 20C
    Melting Point:  234.5F, 112.5C
    Vapor Density (AIR-1):  Not Found
    Evaporation Rate (Butyl acetate-1):   Not Found
    Solubility in Water:  Insoluble
    Flash Point [Method Used]:  Not Found
    Flammable Limits:  Not Found

    Appearance and Odor:  Colorless solid with a musty odor; pure material is
 odorless (NIOSH/OSHA. 1978,  p. 120).

    Conditions or Materials to Avoid:   Not Found

    Hazardous Decomposition or Byproducts:  Thermal decomposition products may
 include chlorine, hydrochloric acid,  and phosgene (Sax, 1984, p. 366).

    Use:  Lindane is used as a pesticide (Havley, 1981, p. 617) and scabicide
    (Hayes, 1982, p.  221).
Synonyms:  (NIOSH/RTECS 1983 Synonyms, Volume 1, p. 1,000):  Cyclohexane,
1,2,3,4,5,6-Hexachloro-, Gamma-Isoraer; Aalindan; Aficide; Agrisol G-20;
Agrocide; Agrocide 2; Agrocide 7; Agrocide 6G; Agrocide III; Agrocide VF;
Agronexit; Ameisenatod; Ameisanmittel Merck; Aparasin; Aphtiria; Aplidal;
Arbitex; BBH; Ben-Hex; Bentox 10; Benzene Hexachloride-gamma-isomer;
gamma-Benzene Hexachloride; Bexol; BHC; gamma-BHC; Celanex; Chloreaene;
Codechine; DBH; Detmol-Extrakt; Detox 25; Devoran; Ool Granule; Drill
Tox-Spezial Aglukon; Ent 7,796; Entomoxan; Exagama; For1in; Gallogama; Gamacid
Gamaphex; Gamene; Gammahexa; Gammahexane; Cammalin; Gamma1in 20; Gammaterr;
Gammex; Cammexane; Gammopar; Gexane; HCCH; HCH; gamma-HCH; Heclotox; Hexa;
Hexachloran; gamma-Hexachloran; Hexachlorane; gamma- Hexachlorane;
gamma-Hexachlorobenzene; 1-alpha,2-alpha,3-beta,4-alpha,
5-alpha,6-beta-Hexachlorocyclohexane; gamma-Hexachlorocyclohexane; gamma-
1,2,3,4,5,6-Hexachlorocyclohexane; Hexachlorocyclohexane, gamma-Isomer;
1,2,3.4.5,6-Hexachlorocyclohexane. gamma-Isomer,; Hexatox; Hexaverm; Hexicide;
Hexyclan; HGI; Hortex; Inexit; Isotox; Jacutin; Kokotine; Xvell; Lendine;
Lentox; Lidenal; Lindafor; Lindagara; Lindagrain; Lindagranox; gamma-Lindane;
Lindane (DOT); Lindapoudre; Lindatox; Llndosep; Lintox; Lorexane; Milbol 49;
Mszychol; NCI-C00204; NEO-Scabicidol; Nexen FB; Nexit; Nexit-Stark; Nexol-E;
Nicochloran; Novigam; Omnitox; Ovadziak; Owadzlak; Pedraczak; Pflanzol;
Quellada; Sang gamma; Silvanol; Spritz-Rapidin; Spruehpflanzol; Streunex; Tap
85; TRI-6; Viton

-------
                 APPENDIX C






SOURCES OF INFORMATION FOR TOXICITY PROFILES

-------
TABLE C-l. TOXICITY PROFILES AVAILABLE FROM U.S. EPA OFFICE
   OF WASTE PROGRAMS ENFORCEMENT (OWPE) AND OFFICE OF
        EMERGENCY AND REMEDIAL RESPONSE (OERR)
ov
CS«aical Cheated
Acta«pbtb«n*
Actfuphtbylcnr
Aettlc arid
4ft tent
At r»l«ln
tue rrlonlcrlle
Aldrla
Aatbraccnt
Aatlaony
Arttnic
AjWtto*
Urlua
»«m«n«
haiidln*
l*nto(*)inehr*c«n(
l«nio(a)pyrcnt
••asotblazolt
Wrjlllu.
• Iplu-IHC
b«t«-»HC
fUU-BHC (Undine)
ttltt-lHC
BuCinp)
•u(v] «crtit>
U4rlur
Ccrbon t«cr»ehlorid*
cl>-Chlord«nr
tr»n»-Chlord»n«
Chlorlnt
CMorobtnztnr
Chlorob«n« ilatc
Cblore«tb«nf
Chlorofor*
p— Chloro-»-crt«o]
l-dloro-3-nttrebcBtcn*
kli (2-ChJor«>«tho»y)«th«Df
Chraviua (total)
ChrMiu* (h«««*«l*at)
OirovluB (triviltot)
OtryMOt
Co«l t«rt
Cob* It
topper
CrtMl
Cy«nld«f
Cycnurle acid
• ,• -BOD
«,p -DDD
• ,. -MI
-,» -CDT
e,s -DOT
Olbroaochloropropan*
,2-Dlch]oreb«nitnf
, )*Dich]orob«nittt«
,*-Dlchlorob«ni«n«
, l-Dichloro«th«n«
2-DlcMorotthant
,i-Pichloro*th]rl*Bt
. ?-cl»-DlchIcr«>«thyl«nt
, 7-tr«ni-OJehlorot thy lent
2,4-Dlchloropb«ool
Z,4-PJehlorophtDory«cetle acid •
1.2-Dtcbleropropanc :
n OEM Itealth
Profile Cffteti A««*«*Mnt

I

Z
I
Z
Z
Z
Z

X
Z
Z
Z
Z
Z

X
X
X
X
X
X

X
X



[
[

-------
TABLE C-l.  (Continued)
                                            oari          oexi i*«uh
                                       Qir»lc«: frofllt  ttftett A«»ti«wnt
1 ,J-Clchloroprop«nf
1 ,3-Cichloroprepaoa
Dleofol
Dialdrla
Di*thyl bcaxanr
Dltthyltn* glycol
Dltthyl phthaJatr
Dlliobutyl kcton*
DlB«thyUslno«thr] »eth*cryl»t«
Ctjittbyl •allla*
Cl»ethjUth*nol
Jtatbyl ehlorldt
2-Krthyl dodceant
Mubyitnt chlorld*
Ktthyl ctbyl b«nxtnc
Krthyl ethyl ktton*
3-Kfthy) b«>ant
H«thyl laebutyl katena
Kathyl itcehaerylata
Hathyl parathlon
2-M*thyl pantana
J— H*thy) pantant
2-Hathyl-l-pantaoa
2-Mathyl tatradccana
2-Hathyl Crldacana







Z

Z
Z
Z
Z
Z

Z
Z
Z

Z
Z




-------
TABLE C-l.  (Continued)
Otf
Oi«»lc»l Ch««lcil
Hone th« no 1 ••ine
IUphtlvil«n«
•ick«]
KUrocelluloie
2-NitrophtDol
Ftntachlorophcnol
Pent«decanf
Ph«Mnthreo«
Phenol
f bitty] ether
fboiphoric acid
Phoiphorwi
Merle acid
Polycblorlnated biphenyl* (Kit)
Folych]orln«t«4 dib«nte-p-4iozln
folycyellc tromttlc bydroccrbon* (FAHt)
Pyrta*
Scltnlua
Silver
todlua chlorite
todlia eycnid*
Sodiu»
ttexidird «ol»«nt
Sulfuric Trlehlore«thaBt
Trlehlere«tbyl«a«
Trichlerefluora««th«a*
2,i,5-Triehleroph«ael
2.4,t-TrichlorepbtBol
2>4(S-Ttlehlereph«B«s7«ettic acid
2,4,3-Tricblorephtnozr proploolc »cld
Trl»«tb7lb«a(«n«
I.3,S-7rlMtbylV«Bi«a«
1 , J,*-Trl»«thTlb«niene
trlf (2,3-Dlbro»opropyJ)phofptutt
Cnd«c«n«
V*n«dlu«
Vinyl chlorldr
Xyltnt
•-lyltn*
e-Xylent
p-Zyltoc
Zinc
ri OCU lUiltb
Profile tffecti Aiiete««nt
I
X
X
s
X

I
X
X
X
X
X
X
X
X

X






X
X
1
Reference:  Life Systems (1985).

-------
                                                  TABLE C-2.  U.S. EPA SOURCES OF TOXICITY PROFILES
         Document
         Availability
                                             Description
Criteria Document - Air
Criteria Docunent -
Drinking Water
Criteria Document -
Ambient Water Quality
Chemical Hazard Informa-
tion Profile (CHIP)

Chemical Profile
Health Advisory
Health Assessment
Document
Office of Air Quality            Simrnry of  the latest scientific  knowledge  on the  effects  of varying quantities of  a  substance  in the air.
Planning and Standards (OAOPS)   Usually prepared for (MOPS by  the Office of Health and Environmental Assessment (OHEA).

Office of Drinking Water (ODW)   Summary of important experimental results from the literature relevant to the chemistry and health effects
                                 of a specific drinking water contaminant.  Serves as a foundation to support regulatory standards or guide-
                                 lines for the acceptable  concentration of the contaminant in the drinking water.
Office of Water Regulations
and Standards (OURS)
Office of Toxic Substances
(OTS)

Office of Waste Programs
Enforcement (OUPE)
CPU
Office of Health and Environ-
mental Assessment (OHEA)
Health and Environmental   Office of Solid Waste (OSU)
Effects Profile
Health Effects
Assessments
Office of Emergency and
Remedial Response (OERR)
Information on the type and extent of identifiable toxic effects on health and welfare expected from the
presence of pollutants in any body of water.   Objective of document is to protect most species in a balanced
and healthy aquatic community and/or to protect human health.

Summary of readily available information concerning the health and environmental effects and potential
exposure to a chemical.

Brief  summary  of the  chemical/physical  properties,  fate and  transport, health effects and environmntal  toxicity
level* for 202 chemicals identified at hazardous waste  sites.  Currently 183 of the planned Chemical  Profiles
are available in draft form.

Develops toxicological analyses to establish  an acceptable level in drinking water for unregulated contaminants
for various exposure durations.

Inventories the scientific literature and evaluates key studies.  Discusses dose-response relationships  so that
the nature of the adverse health response is  evaluated  in perspective with observed environmental  levels.
Usually prepared by OHEA for another office.

Profiles are "mini-" criteria documents prepared usually as summaries of existing water quality criteria
documents.  They serve as a support for the listing of  hazardous wastes in the RCRA program.

Summary of the pertinent health effects information on  58 chemicals found most often at hazardous waste sites.
Developed by the Environmental Criteria and Assessment  Office (ECAO) for OERR.
Address for all offices listed above;  U.S. Environmental  Protection Agency. 401 M Street S.W., Washington, DC  20460   (202) 382-2090

Reference:  Life Systems (1985).

-------
                                          TABLE C-3.  SELECTED CHEMICAL AND TOXICOLOGICAL DATABASES
      Database vendor
                                      Database Name
                                                                                    Database Contents
                                                                                                           Access Procedures
MEDLARS (National  Library
of Medicine)
Toxline
1.5 million references on environmental  and  toxicological
effects of chemicals.
Contact:  MEDLARS Management Section
         National Library of Medicine
         8600 Rockville Pike
         Bethesda, MO  20209
         (301) 496-6193
                             CheMline
                                   An online chemical dictionary of 500,000 records.
                             RTECS (Registry of Toxic Effects
                             of Chemical Substances)
                                   Basic acute and chronic toxicity for more than 57,000 toxic
                                   chemicals.
CIS (Chemical Information
System)
                             AQOIRE (Aquatic Information
                             Retrieval System
CESARS (Chemical  Evaluation
Search and Retrieval System)
Toxicity data for 2,000 chemicals, each cross referenced by
CAS nuifcer.   Lists any studies on bioaccunulation, sublethaI
effects, and environmental fate of the chemical.

Detailed toxicity and environmental fate information and
evaluation on 150 chemicals of importance to Great Lakes.
Contact: CIS,  Inc.
         Fefn-Marquart Associates
         7215  York Road
         Baltimore, HD  21212
         (800) 247-8737
                             CTO> (Clinical Toxicology of
                             Coamercial Products)
                                   Ingredient and product information for most  commercially
                                   available nonfood items.
                             Envirofate
                              ISHOR (Information System for
                              Hazardous Organics in Water)

                              OHMTADS (OiI and Hazardous
                              Materials Technical Assistance
                              Data System)
                                   Information on the environmental fate of approximately 500
                                   chemicals.

                                   Physical and chemical.properties of 14,000 organic compounds
                                   and associated aquatic toxicity data.

                                   Created by U.S. EPA Superfund.  Includes information on
                                   environmental effects of 11,000+ hazardous substances.

-------
TABLE C-3.   (Continued)
CAS Online
(Chemical Abstracts)
Chemical Abstracts
Physical and chemical properties on 6 million chemical
substances.
                                                                                                Contact: Chemical Abstracts Office
                                                                                                         Customer Service
                                                                                                         P.O. Box 3012
                                                                                                         Colunbus, OH  43210
                                                                                                         (BOO) 848-6533
DOE/RECON
35 energy-related and environ-
mental databases including
Energy Database, Water Resources
Abstracts, Environmental Nuta-
gera, and Environmental
Teratology.
                                                             Contact: Technical  Information Center
                                                                      U.S.  Department of Energy
                                                                      P.O.  Box 62
                                                                      Oak Ridge, TN  37380
                                                                      (615) 575-1272
Reference:  U.S. Fish and Wildlife Service (1986).

-------
                    APPENDIX D
EVALUATION OF THE EFFECTS OF COMPOSITE SAMPLING ON
       STATISTICAL POWER OF A SAMPLING DESIGN

-------
APPENDIX D:  EVALUATION OF THE EFFECTS OF COMPOSITE SAMPLING ON STATIST-
                ICAL POWER OF A SAMPLING DESIGN

     Tetra  Tech  (1986b) used  simulation  methods to  make  a direct  comparison  of grab
and  composite-sampling   strategies.    Simulation   refers to  the  use of  numerical  tech-
niques  to  generate  random   variables  with  specified  statistical   properties.    For  the
analyses  described  below, Tetra Tech  (1986b) developed computer programs  to  1)  produce
individual  random  samples  from  populations  with normally  distributed concentrations  of
contaminants, and  other  statistical properties similar to those of  historical bioaccumulation
data  sets  described in  Tetra Tech  (1986b),   2)  construct  composite  samples,  and  3)
calculate statistical power  of sampling designs using individual or composite samples.

     Two  sets  of  analyses were performed  by  Tetra  Tech  (1986b).    In  the  first  set,
simulation  methods  were  used to show the effect of sample  compositing on  the  estimate
of  the  population  mean.   Power  analyses were  used in  the second  set  of  analyses to
demonstrate  the effect  of  increasing  the  number of  subsamples in  a composite  sample
on the probability of detecting  specified levels of differences among stations.

     The  first  set  of analyses demonstrated  that  the  confidence in the  estimate  of  the
mean increases  as  the  number  of  subsamples  in the composite increases  (Figure D-l).
The  simulated  sampling  consisted  of  randomly selecting  10,000 composite  samples from
two  populations exhibiting  two  different  levels   of  variability  in   the sampling  environ-
ment.    The  mean  value  in   both  populations was  fixed  at  J8.52,   but  the population
variances  were  set  at 70.90 or 354.19, corresponding  to  coefficients of  variation  of 45.5
and  101.6,  respectively.   These population characteristics  were  selected  as representative
of the  range of  values  for  the  coefficient of  variation  observed  in  the  historical data
sets  for  selected metals  and organic compounds  in  marine organisms  (Tetra  Tech  1986b).
For  a series  of  individual  fish samples  taken from the  corresponding  populations used
in Analysis 1,  the  95  percent confidence intervals would  range from  1.7  to  35.4  concen-
tration units (e.g.,  ppm).

     To  demonstrate  the effect of sample  compositing  on  the power  of the  statistical
test  of  significance,  Tetra Tech  (1986b)  performed  statistical  power  analyses   using  a
one-way  Analysis  of Variance (ANOVA)  model.   In  these analyses  (Figure D-2),  the
number  of  stations (5), number   of replicate  composite samples  at  each  station  (5),
significance level  of the  test  (0.05),  residual  error variance  level, and level of minimum
detectable  difference (100  percent  of  overall  mean)  were  fixed.  The power  of  the  test
(i.e., the  probability of  detecting the specified minimum difference)  was  then calculated
as a  function of the  number of subsamples constituting each replicate composite sample.

     Power analyses were conducted  for  three levels  of sample variability.   All  design
parameters  except  the  residual  error variance were  identical  in   each  set  of  analyses.
Values  of  the  residual  error variance  were  selected  to  represent  the  range  of  values
found  in  the historical  data  sets described by Tetra Tech (1986b).  The coefficients of
variation selected for these three sets  of analyses were 45.5,  101.6, and 203.5.

     As   shown in  Figure D-2,  the probability of  statistically detecting  a difference
equal  to   the  overall sample  mean  among  stations  increases with   the  collection  of
replicate composite  samples  at each station and as the number of  subsamples  constituting
the  composite increases.   The results  of  both  sets of analyses shown in Figure D-2 also
demonstrate  the  phenomenon  of   diminishing  returns  for   continued  increases   in  the
number  of subsamples   per  composite.    In  Analysis  Set  1,  for  example,  virtually  no

-------
             Analysis 1.   Mean(u)      . 18.52  Coefficient of Variation .455

                       Variance (o*)  • 70.90
    25.
Z


i  •
o
V  15.
                          95% C.I.
                         4           •          10          20


                       NUMBER OF SUBSAMPLES IN COMPOSITE
Analysis 2.   Mean(^)

          Variance (
                                   . 18.52  Coefficient of Variation « 101.6

                                   . 354.19
40 •
< »
Ul
5
o
Ul jo -
H
<
•g
in 10 •
Ul
a-























































                         4          •          10          ao

                        NUMBER OF SUBSAMPLES IN COMPOSITE
Reference: Tetra Tech (1986b)
       Figure D-i Effects of increasing composite sample size on confidence

                   in the estimate of the mean.

-------
                          Analysis
                             1
                             2
                             3
Coefficient
of Variation
   45.5
  101.6
  203.5
                i.o
                o.s
                0.6
                0.4-
                0.0
                  01  2  3  4  S  6  7  ( 9  10 11  12 13  14 IS  16
                            NUMBER OF SUBSAMPLES
                                     (a)
                1.0
                o.t
                0.6-
                0.4-
                0.0
                  0  2  4  6  I  10  12 14  1C 1» 20  22 24 2t  it M
                            NUMBER OF SUBSAMPLES
                                     (b)
Reference: Tetra Tech (19866)
Figure D-2 Power of statistical tests vs. number of subsamples in composite
           replicate samples.  Fixed design parameters: number of stations
           5, number of replicates = 5, significance level = 0.05, minimum
           detectable difference = 100 percent of overall mean value.	

-------
increase  in  the power of  the  statistical  test was achieved  with  increasing  the  subsample
size  above  three.   In  the second  analysis set,  substantial increases  in  statistical  power
were  achieved by  increasing the number  of subsamples in  each  composite from 2  to  10.
However,  with  each  successive  increase  in  subsample  size,  the  relative  benefit  was
reduced  until  very little   was  gained by increasing  the  subsample size  above  10.   For
moderate  levels  of  variability,  6-10 subsamples  within  each  of  5  replicate  composite
samples  may  be adequate  to detect a treatment  difference  equal  to  100 percent  of  the
mean among  treatments.   At  the  highest  level  of variability  analyzed, the collection  of
replicate  composite samples  composed of  25  subsamples each  is  required  to obtain  a
testing power  of 0.80 (Figure D-2).

-------
                    APPENDIX E
EVALUATION OF THE EFFECTS OF SAMPLE REPLICATION ON
       STATISTICAL POWER OF A SAMPLING DESIGN

-------
APPENDIX E:  EVALUATION OF THE EFFECTS OF SAMPLE REPLICATION ON STATISTI-
                CAL POWER OF A SAMPLING DESIGN

      Statistical  power  analysis  can  be  used  to  evaluate  alternative  sampling  designs
with  varying levels  of replication  (Cohen  1977; Gordon et  al.  1980;  Tetra  Tech  1986b).
In  statistical  power  analysis,  relationships  among  the  following study design parameters
are evaluated:

      •    Power   -   Probability  of  detecting   a  real  difference   among treatments
           (e.g., species, stations,  times)

      •    Type  I error  (a)  -  Probability of wrongly  concluding  that  there  are
           differences among treatments

      •    Minimum  detectable  difference  -  Magnitude  of  the smallest difference
           that can be detected  for given power and Type I error

      •    Residual error - Natural variability

      •    Number of stations

      •    Number of replicate  samples.

The analyses  presented below were  conducted  with the objective  of  providing  guidance
in  selecting  levels of  sampling replication.   This objective  was addressed  by determining
the magnitudes  of difference  among  variables  that  can  be  reliably detected  with  varying
levels of sampling effort.

      A  one-way  ANOVA  model  was  used  to evaluate  statistical sensitivity relative  to
level  of sample replication.  Tetra  Tech (1986b,d) provides details  of  the ANOVA  model
and results  of  the   analyses.    All  power analyses were  conducted   using  the   Ocean
Discharge Evaluation System (ODES) maintained by  EPA's Office of Marine and  Estuarine
Protection  (Tetra  Tech 1986d).   The  measure  used to evaluate the  statistical  sensitivity
of  the  monitoring  design  was  the  minimum  detectable  difference  between two mean
values.   To generalize  the results of the power  analysis, the minimum detectable difference
was expressed  as  a percentage of  the  grand mean among  treatments.   The power  of the
test was fixed at 0.80.

      Predicted values  of  minimum  detectable  difference  are  shown for  various  levels of
sample  replication in  Figures  E-l  and E-2.    For  these  analyses,  the Type  I  error  was
fixed   at  0.05.    Minimum  detectable  difference  was  plotted  vs.  number  of  replicate
samples for the following cases:

     •    Number of stations  (or  sampling times) equal  to 4, 6,  8, and 16 stations
           (or times)

     •    Data Variability  Coefficient  (across  treatments)  equal to 30, 50, 70,  and
           90 percent.

The Data  Variability  Coefficient is  equal  to  the  within-groups mean square  divided by
the grand  mean  among groups  (and  multiplied by  100 to  convert to a  percentage).    In
designing a  bioaccumulation study,  the Data  Variability  Coefficient  can  be  estimated by

-------
  <
  ID


  LL
  o
  o

  LU
  rr
  LU
  5    25H

  LU

  CD
  <    200-
 LU
 O
       550
       500
       450
       400
       350-
300-
150-
       100-
       50-
Data Variability
Coefficient
90
70
50
30
Number of Stations
4 6















                      4     6     8     10     12



                     NUMBER  OF REPLICATES
                                              14
16
Reference: Tetra Tech (1986b)
   Figure E-I Minimum detectable difference versus number of replicates

             at selected levels of unexplained variance for 4 and 6

             stations. Power of test = 0.80, significance level = 0.05.

-------
   z
   UJ
  LU
  o
  LU
  cr
  HI
  LL
  LL
  O
  LU
  00
  o
  LU
  LU
  O
       550
       500
       450
400
       350
300
250-
      200-
150-
  i
  z  100
       50-
Data Variability
Coefficient
90
70
50
30
Number of Stations
e 16















                      46      S     10     12
                      NUMBER OF REPLICATES
                                               14
16
Reference: Tetra Tech (1986b)
  Figure E-2 Minimum detectable difference versus number of replicates
             at selected levels of unexplained variance for 8 and 16
             stations. Power of test = 0.80, significance level = 0.05.

-------
performing an  ANOVA  on  available data  from  the literature or  on  a preliminary  data
set.    If  such  data  cannot  be  obtained,   the  average  Coefficient of Variation  (within
groups) can be used as a rough estimate of the Data  Variability Coefficient.

      The  effect  of setting  a different  value for  Type  I error is shown  in  Figure  E-3.
The effect of  changes  in  Type I  error  is greater  for higher  levels  of  data  variability.
Note   that  substantial  increases in   sensitivity  (i.e.,  decreases  in  minimum  detectable
difference) are achieved only for the case of three replicate samples in Figure E-3.

-------
UJ
o
z
UJ
tr
UJ ^
u. £"

5 uj
-I U.
m o
OZ
UJ U
t- o
UJ ff
O UJ
  fi.
s~

s
                                             3 REPLICATES

                                             5 REPLICATES

                                             7 REPLICATES
       80-
       60-
       40-
       20'
               I

             0.05
                   I

                  0.1
 I

02
 \

0.3
0.4
 I

0.5
                         TYPE I ERROR (a)
Figure E-3 Minimum detectable difference versus Type I Error for
          one-way ANOVA design with 3, 5, and 7 replicate samples.

-------
                APPENDIX F
ESTIMATION OF FISH/SHELLFISH CONSUMPTION
        FROM A NATIONAL DATABASE
     (by U.S. EPA Office of Pesticide Programs)

-------
           APPENDIX F:  ESTIMATION OF FISH/SHELLFISH CONSUMPTION
                           FROM A NATIONAL DATABASE
     The EPA  Office  of Pesticide Programs  (OPP) has  evaluated  comprehensive data on
dietary   consumption  of  fish   and  shellfish   within  the  conterminous   United  States.
Selected  consumption rate data  for  the  U.S. population were  used to provide an  overview
of  potential  exposure of  humans  to  toxic  chemicals  associated  with  the  consumption of
contaminated  fish and  shellfish.  Many surveys and reports  were  examined to  determine
probable sources for data on patterns of fish and  shellfish consumption.   Some  economic
reports are  useful only for estimating average fish  and seafood consumption.   In contrast,
polls  have   the  potential  to  provide   estimates   of  individual  consumption   trends  by
consumer, ethnic, or geographical subgroup (Table 1).


DEVELOPMENT OF A NATIONAL DATABASE

     Based  on  sample  size  and  relevance to  recent  trends in  fish  consumption,  OPP
concluded  that  the  most reliable  database for average  daily consumption of  fish  and
shellfish  was  the  U.S.  Department  of  Agriculture  (USDA) Nationwide Food Consumption
Survey of 1977-1978.   In addition to   being relatively  recent,  the USDA  survey  had  a
weighted  sample  size  of  36,000  individuals.    The  consumption  values  listed  in  this
survey are based on 3 days  of individual consumption (from  a  1-day  recall and a 2-day
diary)  gathered  by  interviewers over the course of 1  year.   Although the USDA 1977-
1978  National  Food  Consumption  Survey  is   an  excellent  source of fish  consumption
data,  this survey was conducted  9-10  years ago.   Fish  consumption in the United States
has been rising slowly for several  years.  Based  upon  the  USDA   1977-1978  survey  and
their  National  Food  Consumption  Survey  CSFII  Report  No.  85-3,  the  U.S.  National
Marine  Fisheries  Services  estimated  that average  per  capita consumption of   fish  and
shellfish  increased  from  13  g/day in 1960  to 21  g/day  in  1986.    Because  of  the  nature
of  these  surveys and  limitations  of polls in terms of duration of  individual records  and
numbers  of people surveyed, precise statistical distributions for life-time fish consumption
cannot be obtained with existing  data.

     Consumption  values derived from  the  1977-1978 USDA  study were  used  to develop
EPA's  Tolerance Assessment  System (TAS).   Mean and  percentiles of fish and shellfish
consumption  rates  are  provided in  TAS  for the U.S. population in the  48 conterminous
states and various  population  subgroups (Tables  2-7).   These  estimates  are  for "acute"
consumption  (i.e.,  the  amount  of fish  eaten  in a  single day).   The  average  per  capita
fish/shellfish  consumption  rate  of 15  g/day  in TAS  (No.  4 of  Table  1) is   generally
consistent with the per capita consumption values listed for other surveys and reports.

     The distribution of  consumption   provided in Tables  2-7 is  the  distribution among
fish or shellfish eaters  only, and  is not a distribution  for  the entire population.   The
column  titled "%  Population as  Consumers" provides the  percentage  of  each  population
subgroup  that  is estimated  to  be a consumer  of  each  category  of fish/shellfish on any
given day.   The  mean  consumption estimates  shown  in Tables 2-7  are  also  for eaters
only,  and  should  not be  confused with  the  mean  per  capita consumption  estimates  that
are more commonly used  in TAS analyses.   These  numbers provide valid estimates of
the amounts  of fish  eaten  in a single  day.   However, because of  the  way the data  were
derived,  the  frequency of  fish  consumption  and,  hence,  annual consumption applies  only

-------
                            Table 1 ;   Fish Consumption Data Summary

                                          Survey  Da t a
     Source

1.  USDA Nationwide
   Food Consumption Surwr/
   (for individuals)

note; Figure obtained from
      Environ 1985.
2.  USDA Nationwide Food
   Consumption Survey
   Continuinq Survey of
   Food Intakes by Individuals
   Report I 85-3

3.  USDA NFCS, CSFII
   Report I H6-1 -
Survey
    1977-1978
Averaqe
Consumpt ion
n/day	

  12.0
Extreme
Consumpt ion
q/dciy
    1985
    1986
4. USDA NFCS, CSFII
   Report I 85-2
    1985
  21
  14 (from 1977-1978
      survey above)
  11

  13 (from a CSFII
      concucted in 1985)

  11  (from 1977-1978
       survey above)
  11 (women)
   5 (children)
*Those dates which reflect publication or
 communication rather than the date of the survey
 are enclosed in parenthesis.
 Caveats

Sample size > 36,000
(weighted). Fish and
shellfish in the
conterminous 48 states.
Based on a three day
survey that included
a 1 day recall and a
2 day diary.

Sample size = 658
for men 19-50 only.
1 day recall.
Fish and shellfish.
              Sample size =
              1501 women and 509
              children. This
              survey included
              women 19-50 and
              their children
              1-5. 1 day recall.
              Fish and shellfish.

              Sample size =
              2,210 women, 1,314
              children. This
              survey included
              low income women
              19-50 and their
              children 1-5.
              Fish and shellfish.
                    "--.al1

-------
                                        Table 1 cont.
    Source
Survey Date
 Averaqe
 Consumpt ion
 q/day
Rxtreme
Consumpt ion
q/day
Caveats
5. EPA Tolerance Assessment System
   (computed for a 60kq individual)
    1977-1978
   a. Total  	
   h. Freshwater finfish
                 15.2
                 • 1.8
note; Althouqh the USDA survey fiqure listed is for Pish and
      shellfish/ the TAS data summary includes roe and caviar as well,
      It is unclear whether the USDA fiqure of 12 q/day obtained from
      Environ 19fl5.includes roe and caviar.
                          Based on USDA 1977-
                          1978 NFCS survey.  The
                          discrepency between
                          TAS's 15.2 o/day and the
                          USDA's 12 q/day is due to
                          conversion of the TAS fiqi
                          from q/kq body weiqht/day
                          to q/day by multiplyinq
                          by 60 kq.
6.
USDA's Foods Commonly Eaten (1982) 54
by Individuals: Amounts Per
Day and Per Eatinq Session







	 901
                                                                             Consumers of
                                                                             finfish other
                                                                             than canned,
                                                                             dried or raw.
                                                                             Mean does not
                                                                             equal the median.
                                                                             Sample size ?
note: Obtained from Environ 1985.
7. National Purchase niary
   (analyzed by SRI International)
   a. 95th percentile  	
    1973-1974
14.3
                             41.7
note; Obtained from SRI International.
      It is unclear whether the sample
      size of 25,000 included nonconsumers
      as well as consumers of fish.
           Sample size =
           qreater than 25,000.
           1/12 of the sample
           was surveyed each
           month. It appears
           that this survey was
           for the conterminous
           48 St-

-------
                                  Table i  cont.
    Source
Survey Hate
Averarje
g/day
Extreme
q/day
Caveats
8. National Marine Fisheries
   Service Market Facts Survey
    1969-1970
16.8
   a. 99th percentile --
   h. 99.9th nercentile
                                  - 77
                                  165
   note; The average value of 16.8 q/day was derived from
         Environ, and the extreme finures came from Roland
         Finch's article listed in the reference  section.
         There is'a discrepancy between the 16.8 fiqure and
         the averaqe figure of 14q/day based on the same survey
         ci ted by - Pinch.
              Sample size =
              4,864. Survey
              yielded a per
              capita fish
              consumption figure.
              It is not clear
              whether recreationally
              cauqht fish are
              included. Representative
              households completed
              diaries twice a
              month for I year
              reqardinq fish
              consumption patterns
              at home and outside
              the home.
9. Guide to Eatinq Ontario
   Sport Fish
      1983
13.8
              Sample size
              unknown. Self
              selection biases
              possible. This
              survey is for
              Ontario fishermen
              consumption of
              freshwater finfish.

-------
                                         Table f cont.
    Source
Survey
                                                Average
                                                n/day
Rxtreme
q/day
Caveats
10.  Rnviron 19R5
    Estimate of Humphrey's
    Lake Michigan Data
                                    (1976)
                   45
11.  Personal  Communication
    with R. Sonsteqard
    concerninn intensive
    Lake Ontario sports
    fishermen.
       1187
                                                             373
               Rst ima te is
               extremely rough,
               and is for Lake
               Michigan snorts
               fishermen consumption
               of Lake Michiqan fish.
               Rubiects were selected
               because of how much
               fish they caught.

               Intensive Lake Ontario
               snorts fishermen.
                              TAS MEAT CONSUMPTION VALUES (q/day)
                            a. Red meat
                            b. Poultry -
                            c. Fish 	
                                 134
                                 30.4
                                 15.2

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                                         Table i cont.


                                          Market Data
    Source
Date
Average
q/day
Extreme
q/day
                                                                              Caveats
12.  USDA Agricultural Statistics

    note: Unclear what fish
          connotes.
13.  USDA, ERS, Statistical
   "Food Consumption, Prices,
    and Expenditures."

    note; Unclear whether seafood
          other than fish and
          shellfish included.

14.  National Marine Fisheries
    Service Current fisheries
    Report
    a. Recreationally cauoht
       fish consumption cited
       in 1986 Current Fisheries
       Report table footnote and
       not included in that tablet

15. New York State Department
    of Environmental Conservation
    Average Fish Consumption for
    Recreational Fishermen.

    note: From Environ 1985.
 1983
  18.4
 1985
 1986
 1985
 1984
 1960

 1970
  18.0
  18.1
  17.9
  17.0
  10.3

 3.7-5.3
            32.4
               Per capita
               market data.
               Retail weight.
               Fish.

               Per capita
               market data.
               Edible weight.
               Fish and shellfish.
               Commercial fish
               and shellfish per
               capita. The military
               population is
               excluded and no
               information on fish
               caught through non-
               commercial activities.
                             Based on 90th
                             percentile of
                             nationwide fish
                             consumption figures.
                             The source of the
                             fif    ?s  .,

-------
                                                           TABU 2   CONSUMPTION Of FRCSHUATCR FINFISH
                                         MEAN
                        X POPULATION   CONSUMPTION
POPULATION SUBCROUP:    AS CONSUMERS     C/KC
    ESTIMATED X OF POPULATION Of CONSUMERS VIM CONSUMPTION EXCEEDING X, FOR X>
0    0.?   0.4   0.6   0.8   1.0   1.2   1.4   1.6   1.8     2     3	4     5
U.S. POP. --48 STATES
INFANTS(<1 TEA!)
CHILDIENd 6 TRS)
FENALES(13» TRS)
NAtES(13» f«$)

POPULATION SUBGROUP;
U.S. POP.- -48 STATES
INFAMTS(<1 TEAR)
CHI10REN(1-6 TRS)
FEMALESO3* TRS)
NAIES(13» TRS)
1.10
0.11
0.62
1.14
1.37

X POPULATION
AS CONSUMERS
10.73
0.93
9.36
11.69
10.32
2.7038
2.6724
4.8498
2.4986
2.SS24

MEAN
CONSUMPTION
c/rc
1.7510
4.5676
3.4117
1.4970
1.5181
100
100
100
100
100

0
too
100
100
100
100
100
100
100
too
too
TABLE
98
100
100
98
98
_3 	
ESTIMATED X
0.2 0.4
97
too
99
97
97
91
95
96
90
90
97
100
99
97
95
93
100
98
93
91
CONSUMPTION Of
Of POPULATION
0.6 0.8
84
89
93
82
81
75
83
90
72
71
87 79
100 100
96 93
87 78
04 77
SALTWATER
72
100
93
69
70
64
100
92
62
61
58
44
89
55
54
51
44
84
48
47
30
44
68
27
27
17 10 2
44 0 0
50 32 8
14 7 2
15 8 1
0 0
0 0
3 0
0 0
0 0
flNFISH
OF CONSUMERS WITH
1.0 1.2 1.4
65 56
77 77
86 82
61 51
61 51
47
66
78
41
41
CONSUMPTION
1.6 1.8
40
U
74
34
34
35
58
71
28
29
EXCEEDING
2 3
30
58
67
23
25
14
58
46
9
10
X. FOR X>
4 5 10
740
51 45 6
30 20 3
4 1 0
470
1$ 20 c/rc
0 0
0 0
1 0
0 0
0 0

-------
                                                         TABLE  4  CONSUMPTION OF  SALTUATER FINFISH--DRIED
                                          ME AM
                        X POPULATION   CONSUMPTION
POPULATION SUBGROUP;    AS CONSUMERS       C/KC
     ESTIMATED X Of POPULATION Of CONSUMERS WITH CONSUMPTION EXCEEDING X.  FOR  X*
_0..   0.2   0.4   0.6   0.8   1.0   1.2   1.4    1.6   1.8    2     3      4     5     10     15     20 C/KC
U.S. POP.--48 STATES
INFANTS(<1 TEAR)
CMlLDREN(1-6 TRS)
FEHALES(13* TRS)
MALES(13» TRS)
POPULATION SUBGROUP;
U.S. POP.- -48 STATES
INFANTS(<1 TEAR)
CHILDREN! 1-6 TRS)
FEMALES! 13* TRS)
NALES(1)» TRS)
0.02
0.00
0.00
0.02
0.03
X POPULATION
AS CONSUMERS
0.01
0.00
0.00
0.01
0.00
0.4758
0.0000
0.0000
0.4511
0.5016
MEAN
CONSUMPTION
C/KG
2.3449
0.0000
0.0000
2.S632
0.7346
100 26
0 0
0 0
100 25
100 27
TABLE
26 26
0 0
0 0
25 25
27 27
26
0
0
25
27
26
0
0
25
27
26
0
0
25
27
5 CONSUMPTION OF FISH-ROE
ESTIMATED X Of POPULATION
0 0.2 0.4 0.6 0.8
100 100
0 0
0 0
100 100
100 100
100 100
0 0
0 0
100 100
100 100
85
0
0
100
. 0
OF
1.0
85
0
0
100
0
26
0
0
25
27
.CAVIAR
CONSUMERS WITH
1.2 1.4
85
0
0
100
0
69
0
0
100
0
6
0
0
13
0
0
0
0
0
0
CONSUMPTION
1.6 1.8
69
0
0
100
0
69
0
0
100
0
0
0
0
0
0
0
0
0
0
0
EXCEED INC
2 3
69
0
0
100
0
38
0
0
42
0
00000
00000
00000
00000
00000
X, FOR X*
4 5 10 15 20 GAG
15 0 0 0 0
00000
00000
00000
00000

-------
                                        MBit  6  CONSUMPTION Of SHELLFISH
                  MEAN
X POPULATION   CONSUMPTION
ESTIMATED X OF POPULATION OF CONSUMERS WITH CONSUMPTION EXCEEDING X, FOR **
                                                                     4
U.S. POP.- -48 STATES
iNFAJtrs(«EN(1-6 T(S)
FCHALES(13» TBS)
MALES(I3» TRS)

POPULATION SUBCHOUP:
U.S. POP.- 44 STATES
INfANTS(
-------
to the  "average" person.   It  is  not  possible to predict  from  that  survey the population
distribution for frequency of consumption and range in annual consumption.


ESTIMATION OF LOCAL CONSUMPTION

     Since  the  estimates  of fish consumption  just  discussed  are  national  averages, they
are not  predictive  of all  subgroups and regions on a scale fine enough to address local
situations of potential  concern.   If  local fish  consumption information  is not  available,
the  Fish  Contamination  Subcommittee  of  the Risk Assessment  Council suggests  that
other estimates  of  extreme  consumption can  be made by  assuming that fish  consumption
by some  subgroups would be equal to  the average consumption of red  meat (130  g/day)
and, as  a "reasonable"  worst case, that  some people  would consume  fish at  levels equal
to the  combined TAS  average consumption of red meat,  poultry,  and fish/shellfish (180
g/day)  (Table  8).   Conceivably,  these values  could be  exceeded locally,  especially when
economically disadvantaged  people  rely  on fishing  to survive.   Adding on  an  additional
equivalent for  egg consumption  would bring the average  estimate  up to 215  g/day,  and
this  might  not  be  unreasonable  for  special  situations.   The  above  values are  based  on
consumption by an average 60-kg individual.

     Based  on  114  g  (0.25  pound)  for a  single serving  of  fish/shellfish,  an  average
annual  consumption  of 18  g/day  (e.g., see Data  Source   Nos.  12  and  13  of  Table  1)
corresponds to  approximately  1  meal  per week of  fish  or  shellfish.   Using  the TAS
estimate  of 180  g/day   for  total meat  protein  consumption  (consisting  of  red meat,
poultry,  and fish/shellfish),  and  an estimate  of 114 g for an average single  serving,  the
total average meat consumption corresponds  to about  11  meals per week.

-------
                                                      Table 8


                                               Fi sh Cbnsumpt ion - TAS


                              g/day/kg body weight     g/dayl    meals/year!  (assuming a meal size
                                                                               of approximately 4
                                                                               ounces or 114 grams)
1.  EPA TAS Average                   0.25              15           48
    Per capita
    Fish/shellfish
2.  EPA TAS Average                   2.2              130          420
    Per capita
    Red meat

                                      3.0              180          580
3.  EPA TAS Average
    Per capita
    Red Meat + Poultry + Fish
1 Based on TAS values for average consumption presented in g/day/kg body weight and adjusted to g/day
  for a 60 kg individual.

-------
                              References


 Dykstra,  William.  January 12,  1982.  "Ferriamicide; Request
      for  Conditional  Reaistration; EPA Req. No.  38962-RR",
      Internal  Memorandum  to Georqe LaRocc*.

 Environ Corporation.  19^5. Fish Consumption by Recreational
      Fishermen:  An Example of  Lake Ontario/Niaara River  Reaion.
      Prepared  for  US EPA Office of Enforcement and Compliance
      Mon i to r i na.

 Pinch, R.,  1973. Effects  of Reoulatorv Guidelines on  the  Tntak<=> of
      Mercury  from  Fish -  the  MECCA Proiect, N'1FS, Fishery
      Bulletin, Vol.  71, No. .3, pn. 615-626.

 Metzqer, Michael.,  March  25,  19R7. "Fish Action  Level Reevaluation
      for Aldrin/Dieldrin, Chlordane, DOT, Heptachlor, and Mirex.  o
      Accession Number RCR Numbers 205ft, 20fi2, 2063, 2064,
      2065 and 2066.", Internal Memorandum to Jack Housenaer.

 Ontario Ministry of  the Environment. 19R4. Guide to Eatinq Ontari
      Snort Fish, 1984-1985. Southern Ontario, Great Lakes.

 Page, N.; Cavender,  F.; Cook, R. 1985.  Carcinoaenic  Risk Assess™ i
      for Aldrin and Dieldrin.  Unpublished study prepared by Dynaiua<
      Corp. under EPA Contract No. 68-02-4131.

 Sonsteqard, R. , Tufts University, Boston, Massachusets.  Personal
      communicat ion.

 SRI International.  1980. Seafood Consumntion Data Analysis
      (Final Report). Prepared for USEPA, under EPA Contract No.
      68-01-3887.

USOA. 1984. Agricultural Statistics* Consumption and  Family
      Li vino i Table 697, p"I 506.

USDA. 1985. ERS, Statistical Bulletin 749.  Food Consumption,
      Prices and Expenditures. Table 7, p. 13.

fJSDA. 1985. Nutrition Monitorina Oivision, Hunan Nutrition Informat
      Service. FOOD ANO MtJTRIF.NT INTAKES: INDIVIDUALS  IN FOrjR
      1977-1978. Report No. 1-3.

USDA. 1936. Nationwide Food Consumption Survey Continuina
      Survey of Food Intakes by Individuals, Men 19-50 Years,
      1 Day 19R5. NFCS, CSFH Report No. 85-3.

-------
USDA. 1986. Nationwide Food Consumption Survey Conf.inuina Survey
     of Food Intakes by Individuals,  Low-Income Women 19-50 Years
     and Their Children 1-5 Years,  1  Day 1985. NFCS,  CSFII report
     No. 85-2.

USDA. 1987. Nationwide Food Consumption Survey Continuing Survey
     of Food Intakes by Individuals,  Women 19-50 Years and Their
     Children 1-5 Years, 1 Day 1,986.  NFCS, CSFII Renort No. 86-1.

USDC. 1987. National Oceanic and Atmosoheric Administration,
     National Marine Fisheries Service. Fisheries of  the United
     States, 19*5, Current Fisheries Statistics No.  83«5.

-------
              APPENDIX G
EPA OFFICE OF RESEARCH AND DEVELOPMENT,
 ENVIRONMENTAL RESEARCH LABORATORIES

-------
              EPA OFFICE OF RESEARCH AND DEVELOPMENT,
                ENVIRONMENTAL RESEARCH LABORATORIES
Region 1       Environmental Research
                 Laboratory/ORD
               South Ferry Road
               Narragansett,  RI  02882
               FTS: 8-838-5087
               DDD:(401) 789-1071

Region 4       Environmental Research Lab/ORD
                 Laboratory/ORD
               Sabine Island
               Gulf Breeze, FL  32561
               FTS: 8-686-9011
               DDD:(904) 932-5311

Region 5       Environmental Research Lab/ORD
                 Laboratory/ORD
               6201 Congdon Boulevard
               Duluth, MN  55804
               FTS: 8-780-5550
               DDD:(218) 720-5550

               Environmental Ecological and
                 Support Laboratory/ORD
               26 W. St.  Clair Street
               Cincinnati, OH 45268
               FTS: 8-684-7301
               DDD:(5J3) 569-7301

Region 6       Robert S. Kerr Environmental
                 Research Laboratory/ORD
               P.O. Box  1198
               Ada, OK  74820
               FTS: 8-743-2011
               DDD:(405) 332-8800

Region 10      Environmental Research
                 Laboratory—Corvallis/ORD
               200 S.W. 35th  Street
               Corvallis, OR  97333
               FTS: 8-420-4601
               ODD:(503) 757-4601
Environmental Research
  Laboratory/ORD
College Station Road
Athens, GA 30613
FTS: 8-250-3134
DDD:(404) 546-3134

Center for Environmental
  Research Information/ORD
26 West St. Clair Street
Cincinnati, OH  45268
FTS: 8-684-7391
DDD:(513) 569-7391
Pacific Division - Environ-
  mental Research Lab/ORD
Hatfield Marine Science
Marine Science Drive
FTS: 8-867-4040
DDD:(503) 867-4040

-------
                  APPENDIX H
EPA REGIONAL NETWORK FOR RISK ASSESSMENT AND
           RISK MANAGEMENT ISSUES

-------
                        EPA REGIONAL NETWORK FOR
                 RISK ASSESSMENT/RISK MANAGEMENT ISSUES
Region
Senior Contact
Staff
Other Memberships
   I     Paul Keough
         Deputy Regional Admin.
         J.F. Kennedy Federal Bldg.
         Room 2203
         Boston, MA 02203
         (FTS) 835-3402
         E-Mail EPA9102

   II     Alice Jenik, Acting Chief
         Policy & Program
         Integration Branch
         26 Federal Plaza
         New York, NY 10278
         (FTS) 264-4296
         E-Mail EPA9243

  III     Greene Jones,  Director
         Environmental Services Div.
         841 Chestnut Bldg.
         Philadelphia, PA  19107
         (FTS) 597-4532
         E-Mail EPA9380
  IV     Lee DeHihns3'*
         Deputy Reg. Admin.
         345 Courtland St., N.E.
         Atlanta, GA 30365
         (FTS) 257-4727
         E-Mail EPA9400

  V     Bill Sanders, Director
         Environmental Services Div.
         230 South Dearborn St.
         Chicago, IL  60604
         (FTS) 353-3808
         E-Mail EPA9580
                        Tom D'Avanzo, Chair
                        Toxics Coord. Comm.
                        (FTS) 835-3222
                        E-Mail EPA9136
                        Maria Pavlova
                        Office of Emergency &
                        Remedial Response
                        (FTS) 264-1918
                        E-Mail EPA9231
                        Roy Smith
                        Environmental Scientist
                        Environmental Serv. Div.
                        (FTS) 597-9857
                        E-Mail EPA9381
                    Barbara Beck1
                    Toxicologist
                    Air Management Div.

                    Harley Laing5
                    Director
                    Planning & Mgmt. Div.

                    Bill Muzynski2
                    Deputy Regional
                    Administrator
                    Stan Laskowski3
                    Deputy Regional
                    Administrator

                    Steve Wassersug2
                    Director, Hazardous
                    Waste Management
                        Susan Deihl
                        Risk Assessment Coord.
                        Office of the Regional
                        Administrator
                        (FTS) 256-3776
                        E-Mail EPA9400

                        David  Dolan (5S-PTSB-7)
                        Environmental Scientist
                        Pesticides & Toxic Substances Branch
                        (FTS) 886-5518
                        E-Mail EPA9575

                        Milt Clark  (5HT)
                        Chairman,  Health Effects Forum
                        Pesticides & Toxic Substances Branch
                        (FTS) 886-3388
                        E-Mail EPA9575

-------
   VI
   VII
  VIII
   IX
Allyn M. Davis, Director
Hazardous Waste
Management Division
120J Elm Street
Dallas, TX 75270
(FTS) 729-2730
E-Mail EPA9650

William W. Rice
Deputy Region. Admin.
726 Minnesota Avenue
Kansas City, KS  66101
(FTS) 757-2800
E-Mail EPA9703

Alexandra Smith3
Deputy Region. Admin.
One Denver Place
Denver, CO  80202-2413
(FTS) 564-2413
E-Mail EPA9802
Jill Lyons
Toxics Coordinator
Air Programs Branch
(FTS) 729-9187
E-Mail EPA966J
Bob Fenemore
Air & Toxics Div.
(FTS) 757-2835
E-Mail EPA9761
Jim Baker
Waste Management Div.
(FTS) 564-1518
E-Mail EPA9873

Suzanne Wuerthele
Air & Toxics Div.
(FTS) 564-1743
E-Mail EPA9850
Frances Phillips4
Acting Regional
Administrator
Art Spratlin6
Director
Air & Toxics Div.
Arnold Den
Senior Science Advisor
Office of the Regional Administrator
215 Fremont Street
San Francisco, CA  94105
(FTS) 454-0906
E-Mail EPA9900
          Randy Smith5, Chief
          Hazardous Waste Policy
          Branch
          1200 6th Avenue
          Seattle, WA  98101
          (FTS) 399-1261
          E-Mail EPA9401
                             Elaine Somers
                             Program Analyst
                             Management Division
                             (FTS) 399-2966
                             E-Mail EPA9021

                             David Tetta
                             Environmental Engineer
                             Environmental Services Div.
                             (FTS) 399-1597
                             E-Mail EPA9051
JRisk Assessment Forum
'Risk Assessment Council
'Risk Management Council
^Agency for Toxic Substances Disease Registry
Comparative Risk Task Force
Reference:  U.S. EPA 1987b.

-------
                        APPENDIX I
COMPILATION OF LEGAL LIMITS FOR CHEMICAL CONTAMINANTS IN
                FISH AND FISHERY PRODUCTS

-------
         TABLE 1-1. COMPILATION OF LEGAL LIMITS FOR HAZARDOUS
                    METALS IN FISH AND FISHERY PRODUCTS
Metals (DOW)
Country
Austral ia*
Brazil
Canada
Chile
Denmark
Ecuador
Finland
France
Germany
Greece
Hong Kong
India
Israel
Italy
Japan
Korea
Netherlands
New Zealand
Phil Ippines
Poland
Spa In
Sweden
Switzerland
Thailand
United Kingdom
United States
U.S.S.R.
Venezuela
Zambia
Range
Minimum
Max imum
As Cd Cr
1.0,1.5" 0.2-5.5

3.5
0.12,1.0 0.5

1.0
5.0

0.5

1.4-10 2.0 1.0
1.0




0.05-1.0
1.0 1.0
3.0
4.0


0.1
2.0
1.0


0.1 0,0.1
3.5-5.0

0.1 0 1.0
10 5.5 1.0
Cu
10-70


10

10





10





30

10-30



20
20


10
100

10
100
H9
0.5,1.0
0.5C
0.5

0.5
1.0
1.0
0.5,0.7
1.0
0.7
0.5
0.5C
0.5
0.7C
0.3.0.4C
0.5
l.OC
0.5C
0.5

0.5
l.OC
0.5
0.5

l.OC
0.2-1.0
0.1-0.5
0.2-0.3

0.1
1.0
Pb
1.5-5.5

0.5
2.0

5.0
2.0

0.5

6.0
5.0

2.0


0.5,2.0
2.0
0.5
1.0-2.0

1.0-2.0
1.0
1.0
2.0-10


2.0
0.5-10

0.5
10
Sb Se Zn
1.5 1.0,2.0 40-1,000


0.05,0.3 100






1.0
50





1.0 2.0 40

30-50




50



100

1.0 0.05 30
1.5 2.0 1,000
• Limit varies among  states.
b Inorganic.
C Total.
References:  Nauen (1983); U.S. Food and Drug Administration (1982, 1984).

-------
TABLE 1-2. COMPILATION OF LEGAL LIMITS FOR ORGANIC PRIORITY POLLUTANTS
                AND PESTICIDES IN FISH AND FISHERY PRODUCTS (ppm)
HeiKhloro-
btnitnt Kit ROD
CM*d* 2.0 20*
OvMWk
C«r««i/< O.S
Inland
tetkcrltmlt 4.0
SMdM 0.2 2.0-4.0
fellicrlMd 1.0
ItUllMd
••ng*

Mtitodi O.S 4.0 20*
HrpUcklor/
Aldrl*/ Hrpl«hlor- HCH
Oleldrta CDIordwr 001 OOC 000 OOlt fndrki rpo> id« (rponr (1 lC l»r (Iktr •ffwfe (lMllc
-------