United States       Office of Water         April 1983
            Environmental Protection   Regulations and Standards (WH-553)  EPA-440/4-85-021
            Agency         Washington DC 20460
            Water
&EPA      An Approach to
            Assessing Exposure
            to and Risk of
            Environmental Pollutants

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                                     DISCLAIMER

This is a contractor's final report, which has been reviewed by the Monitoring and Data Support
Division, U.S. EPA.  The contents do not necessarily reflect the views and policies of the U.S.
Environmental  Protection Agency,  nor  does mention of trade names or commercial products
constitute endorsement or recommendation for use.

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                                           EPA-440/4-85-021
                                           July  1980
                                           (Revised April 1983)
      AN APPROACH TO ASSESSING EXPOSURE TO AND

         RISK OF ENVIRONMENTAL POLLUTANTS
                      by

            Arthur D.  Little, Inc.
               Michael  Slinak
               Project  Manager
    U.S. Environmental Protection Agencv
       U.S. EPA  Contracts 68-01-3857
                          63-01-5949
Monitoring and Data Support Di'/ision (WH-553)
  Office of Water Regulations and Standards
           Washington, D.C.  20460
  OFFICE OF WATER REGULATIONS AND STANDARDS
              OFFICE OF WATER
    "J.S.  ENVIRONMENTAL PROTECTION AGENCY
           WASHINGTON, D.C.  20460

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                                 FOREWORD
       Effective regulatory action for toxic pollutants requires an under-
  standing of the ecosystem and human health risks associated with the
  manufacture, use, and disposal of the substance.  The process of assessing
  these risks needs to develop information on the fluxes of the substance
  through the technosphere and through the biosphere, and to couple this
  with information on its biological effects.   The analysis is thus in-
  tended to allow an informed judgment about the likelihood of environmental
  harm and to provide insight into the potential effectiveness of alternative
  actions to control or reduce any unacceptable risks.

       This document describes the exposure/risk assessment methodology
  ?™6 T  aS ?a" °f 3 Pro«"» to addr^s 65  classes of chemicals (or
  129  individual 'priority pollutants")  named  in the 1977 Clean Water  Act.
  The  methodology is multi-media in scope,  enabling all facets of environ-
  mental risk to be viewed in perspective.

     _  The methodology begins  by identifying releases  to  the  environment
  during production,  use,  or  disposal  of  the substance.   It  proceeds with
  evaluating  the fate of  the  substance in the environment  and  the  resulting
  ambient levels.   It  then predicts  the human and  aquatic  life  exposure to
  the  substance  and, after  interpreting the  available data  on  toxicity
  provides  an  assessment of risks.

       The  methodology  has been applied to  the nationwide  assessment of
  several dozen  of  the  priority pollutants, and numerous examples  taken
  hlvl  bt" fr\have befn P^ented.  The analytical  elements, however,
,have  been found to apply readily to local, as well as nationwide studies.

                         Michael W. Slimak, Chief
                         Exposure Assessment Section
                         Monitoring & Data Support Division (WH-553)
                         Office of Water Regulations and Standards
                                   iii

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                            TABLE OF CONTENTS
                                                                      Page
 LIST OF  FIGURES
                                                                      ix

 LIST OF  TABLES                                                        ±±

 ACKNOWLEDGMENTS                                                      xvi

 1.0  TECHNICAL SUMMARY

 2.0  INTRODUCTION

      2.1  Background
      2.2  Types of Exposure and Risk Assessments                    l~]
      2.3  Report Objectives and Content                             ?~^


 3.0  EXPOSURE AND RISK ASSESSMENTS—AN OVERVIEW                     - ,
                                             ~                       J—i
      3.1   Overview
      3.2   Initial Considerations  in  a Risk Assessment               l~l
      3.3   Materials  Balance Environmental  Loadin^                    i_-
      3.4-  Monitoring Data                        3
      3.5   Environmental Pathways  and  Distribution                    \~J7
     3.6   Exposure of  Humans and  Other  Biota                         o
     3.7  Health  and Environmental Effects                           ,7.,
     3.3  Risk Considerations                                        ,  ;.
     3.9  Presentation of Risk Assessments                           3~^

4.0  MATERIALS BALANCE-SOURCE IDENTIFICATION AND LOADING
     ESTIMATION
                                                                     4-1
     4.1  Introduction
     4.2  Goals of a Materials  Balance                               ^~\
     4.3  Materials Balance Methods                                  ,
     4.4  Examples of Materials Balance Output                      7~-
          4.4.1  Introduction                                       "
          4.4.2  Chloroform                                         ^~^
          4.4.3  Copper                                             7~-
          4.4.4  Pentachlorophenol                                  7~^i
     4.5  Selected Examples  from Materials  Balances  for Other       '"'""
          Pollutants
          4.5.1  Releases during Transportation                      4!^
          4.5.2  Public-ly Ovnea Treatment Works                      ^q
          4.:>.j Natural and Inadverzant Releases                    7_]X
          ^.5.4 Releases to  the Atmosphere                          7~-5r,
     References                        '                              -+--50
                                                                    4-32
                                    v

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                    TABLE  OF  CONTENTS  (Continued)
 5.0   ENVIRONMENTAL PATHWAYS AND FATE ANALYSIS
7.0  HUMAN EXPOSURE AND EFFECTS
                                                                     3-1
     5.1   Introduction                                               5_]_
     5.2   Goals of Environmental Pathway and Fate Analysis           5-4
     5.3   Environmental Pathway and Fate Analysis Methods            5-5
           5.3.1  Environmental Scenario/Case Example Method          5-6
           5.3.2  Critical Pathway/Distribution Estimation Method     5-9
           5.3.3  Modeling Approaches                                 5-12
     5.4   Examples of Environmental Pathways and Fate Analysis       5-14
           5.4.1  Environmental Scenario Method                       5-1-
           5.4.2  Critical Pathway/Distribution Estimation Method     5-13
           5.4.3  Modeling Approaches                                 5-19
                 5.4.3.1  Phthalate Esters                           5-19
                 5.4.3.2  Dichiorobenzenes                           5-21
     References                                                      5-^5

6.0  MONITORING DATA AND ENVIRONMENTAL DISTRIBUTION                  6-1

     6.1   Introduction                                               6_]_
     6.2  Goals and Objectives                                       £_••>
     6.3  Methods and Approaches                                     5-3
     6.4  Examples of Monitoring Data                                6-5
          6.4.1  Copper and Silver                                   5-5
          6.4.2  Pentachlorophenol                                   6-11
          6.4.3  Dichloroethanes                                     6-13
     References                                                      6-16
                                                                    7-1
     7.1  Introduction                                              7_]_
     7.2  Goals and Objectives                                      7.3
          7.2.1  Human Exposure Analysis                            7-3
          7.2.2  Human Effects Analysis                             7-4
     7.3  Approaches and Methods                                    7-4
          7.3.1  Exposure Analysis                                  7-4
                 7.3.1.1  General Approach                          7-i
                 7.3.1.2  Sources of Exposure,  Exposure Routes
                          and  Subpopulation Groups                   7-7
                 7.3.1.3  Exposure Levels  from  Major Exposure
                          Routes                                    -_S
                 7.3.1.4  Summarizing Exposure                       7-2S
          7.3.2  Effects Analysis                                   7-23
                 7.3.2.1  General Approach                          7-28
                 7.3.2.2  Details of Approaches and  Examples         7-38
     References                                                     7-61
                                  VI

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                     TABLE OF CONTENTS (Continued)


 8.0  EXPOSURE AND EFFECTS—NON-HUMAN BIOTA

      8.1  Introduction                                              g,
      8.2  Goals  and Objectives                                      Q_T
           8.2.1   Exposure Analysis                                   g_3
           8.2.2   Effects  Analysis                                    g_3
      8.3  Approaches  and  Methods                                     g_4
           8.3.1   Overview                                           g_^
           8.3.2   Effects  Analysis                                    g_5
                  8.3.2.1   Data Collection  and  Preliminary Data
                           Review                                     g_r
                  8.3.2.2   Critical Data Review and Tabulation        8-7
                  8.3.2.3   Summary of  Effects                         3-3
           8.3.3   Exposure  Analysis                                   3-1?
                  8.3.3.1   Introduction                               8-12
                  8.3.3.2   Identification of Sensitive Species        8-14
                  8.3.3.3   Identification of Areas with Expected
                           or Measured High Concentrations            8-14
                  8.3.3.4   Identification of Factors Modifying
                          Availability                   '   °        8-lb
                  8.3.3.5  Identification of Locations in Which
                          Risk to Aquatic Organisms is Likely
                          to Occur                                  8-19
          8.3.4  Terrestrial Effects and Exposure Analysis           8-19
     References                                       '              a T

9.0  RISK CONSIDERATIONS                                            9-1

     9.1  Introduction                                              „_,
     9.2  Goals and Objectives                                       o_0
     9.3  Approaches and Methods                                    o_2
          9.3.1  General Considerations                              9_3
                 9.3.1.1  Definitions  of Risk                        9.3
                 9.3.1.2  Overview of  Evaluation  Approaches          9-4
                 9.3.1.3  Approaches Described  in the  Literature     9-7
          9.3.2  Evaluation of  Risk  to Human Health                  9.3
                 9.3.2.1  Overview                                   o_8
                 9.3.2.2  Qualitative  Risk Analysis                  9-9
                 9.3.2.3  Semi-Quantitative Risk  Analysis            9-10
                 9.3.2.4  Quantitative Risk Analysis                 9_n
          9.3.3   Evaluation  of  Risk for Aquatic Species              9-70
          9.3.4   Summary of  Risk Considerations                      Q_O/,
    References                                                      " ^_
                                  VII

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                      TABLE OF CONTENTS (Continued)



                                                                   Page

10.0  BIBLIOGRAPHY OF REFERENCE MATERIALS  FOR USE IN EXPOSURE
      AND RISK ASSESSMENTS                                         10-1

      10.1  Introduction                                           10-1

      10.2  Materials Balance                                      10-2

      10.3  Fate and Pathways Analysis                             10-6

      10.4  Monitoring Data and Environmental Distribution         10-10

      10.5  Human Exposure and Effects                             10-12

      10.6  Effects and Exposure—Non-Human Biota                  10-15

      10.7  Risk Estimation                                        10-16

 APPENDIX A.   MATHEMATICAL DETAILS OF  RISK CALCULATIONS             A-l

       A.I  Introduction                                           A-l
       A.2  Human Equivalent Doses           '                      A-2
       A. 3  One-Hit Models                                         A-5
       A.4  Linear Extrapolation                                   A-6
       A.5  Log-Probit Extrapolation                               A-9
            References                                              A-14
                                  viii

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                                    Page
                            LIST OF FIGURES

Figure
  No.

  1-1       Major Components in Environmental Exposure and
           Risk Assessment

  3-1       Overview of Environmental Risk Assessment Process

  3-2       Example  of  Materials  Balance Checklist                    3-6

  3-3       Schematic Example  of  Fate and Pathways Analysis            3-9

  3-4       Human Exposure  Matrix                                     3-1?

  4-1       Generalized Materials Balance Flow Diagram Showing
           Typical  Releases                                           4_9

  4-2       Materials Balance Methodology Flow Chart                   4-6

  4-3       Example  of  Graphic Representation of Materials Balance
           Output—Environmental Loading  of Chloroform, 1978    ~     4-16

  4-4       Example  of  Graphic Representation of Materials Balance
           Output—Environmental Loading of Copper, 1976              4-10

  4-j       Example of Geographic Distribution of Production           4-2.°
           Sources—Locations of Pentachlorophenol Manufacturing
          and Wood Treatment Plants

 4-6      Example of Regional Distribution of Use Sources-
          Regional Estimated Consumption of Pentachlorophenol
          by Wood Preservation Plants                  '             £_?.

 4-7      Example of End Use Data—Materials  Treated with
          Pentachloropehnol,  1978                                    /._-.,;

 4-8      Example of Regional Consumption Data—U.S.  Regional
          Consumption  of Wood Treated with Pentachlnroohenol*
          1978                                         '   "           ,  „„

 5-1      Example of Environmental  Pathways and Fate  Analysis-
          Major  Environmental Pathways  cf Trichloroethylane          5-2

 5-2      Diagram of Environmental  Scenario Approach  to Pathways
          and Fate  Analysis                                   ' "     -_-,

 5-3       Diagram of Critical Pathway/Distribution Estimation
          Method  for Environmental  Pathways and Fate Analysis        5-10

 5-4       Example of Environmental  Scenario Identification—
          Schematic Diagram of Major Pathways of Copper Released
          to the  Environment by Human Activities   "'                "-!'
ix

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                     LIST OF FIGURES (Continued)

Figure
  No-                                                               Page
 5-5
Example of Environmental Scenario Analysis—Typical       5-16-
Environmental Pathways of Copper                          ^-17
 5-6      Example of Use of Simple Quantitative Model to Estimate
          Environmental Distribution—Ground-Level Concentrations
          of Pentachlorophenol  in the Plume  Downwind  of a Cooling
          Tower (Two Source Heights)

 5-7      Example of Results of Modeling  of  Environmental Distri-
          bution—Comparison of Calculated and  Observed Levels
          of Di(2-ethylhexyl)phthalate  in Air,  Sediment,  Water,
          and Fish                                                  5-2?

 6-1      Example of Surface Ivater Monitoring Data Distribution
          by Concentration  Ranges—Copper, 1970-1979                 6-6

 6-2      Example of Geographic Distribution of Monitoring Data
          for Silver                                                g_-

 7-1      Example of Graphic Summary of Routes  of  Human  Exposure
          to Lead                                                   7-29

 7-2      Example of Graphic Summary of Estimated  Exposures to
          Lead  for the  General  Adult Population                     7-30

 7-3      Example of Graphic Summary of Estimated  Exposures to
          Lead  for a Specific Subpopulation  (Children with Pica)     7-31

 7-4      Flow  Chart for Carcinogenic Risk Evaluation                7-42

 7-5      Flow  Chart for Mutagenicity Risk Evaluation                7-45

 7-6      Flow  Chart for ,,Teratogenicity Risk Evaluation              7-50

 7-7      Flow  Chart  for General Evaluation of Chronic Functional
          Disorders                                                  7-55

 7-8      Possible Protocol  for Evaluation of Data on Chronic
          Functional Disorders Resulting from Dermal Absorption      7-56

3-1      Flow Chart  of Methodology for  Effects  and Exposure
         Analysis for Non-Human Biota                 '              Q z
                                                                   fj ~*O

3-2      Example of  Graphic Presentation  of  Overlap Between
         Observed Concentration and Water Oualitv  Criteriou
         for the Protection of  Aquatic  Life—Zinc                   $-17
O-1
         Flow Chart for Developing Risk  Considerations              9-6

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                      LIST OF FIGURES  (Continued)
Figure
No.                                                                  D
	                                                               Page_

9-2    Example of Risk Considerations Summary for Aquatic            9.95
       Biota—Arsenic Exposure and Toxicity to Aquatic
       Organisms

A-l    Cumulative Distribution Function (Px, t)                      A-3

A-2    Log-Probit Form for Dose-Response Curve                       A-10
                                 xi

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                           LIST OF TABLES
Table
 No.
                                                                    Page

 2-1      Parameters chat Characterize Risk Assessments             2-3

 3-1      General Goals of Environmental Risk Assessment            3-2

 4-1      Example of Source and Environmental Loading Matrix:
          Phthalate Esters                                           _
 4-2
5-2
 Source  Identification  for Materials Balance Matrix
 4-3       Example  of  Materials  Balance  Output  Involving  Inadver-
          tent  Releases—Estimated  Production  and  Use/Release  of     4-14-
          Chloroform,  1978                                           4_15

 4-4       Example  of  Commercial Production and Use Data—Summary
          of U.S.  Copper Supply and Demand,  1976                "     4-17

 4-5       Example  of  Materials Balance  Output  Involving  Natural
          Sources—Estimated Environmental Releases of Conner        '-*-•> 8
          1976


 4-6       Example  of Materials Balance  for Publicly Owned Treat-
          ment Works:  Zinc                        '                  4-?]

 5-1       Example  of Results of Modeling of Environmental Dis-
          tribution—Comparison of Results from MacXay's Equili-
          brium Model and EXAMS for 1,2-Dichlorobenzene  in a
          Pond Svstem
Example of Results of Modeling of Environmental Dis-
tribution—EXAMS Output for 1,2-Dichlorobenzene
                                                                   5-23
                                                                   5-24
6-1      Example of Surface Water Monitoring Data Distribution
         by Major River Basins—Copper                             g_g

6-2      Example of Sediment Monitoring Data Distribution by
         Major River Basins—Copper                        "        5.9

6-3      Example of Surface Water Monitoring Data for Copper bv
         Minor River Basins                                   '     6_1(

6-4      Example of Monitoring Data for Food and Feed—Penta-
         chlorophenol                                              g_--

6-5      Example cf Monitoring Data for Human Tissue and
         Urine—Pancachloropher.ol                                  A_T -
                                 xii

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                       LIST OF TABLES (Continued;
 Table
  No.
  6-6       Example of Ground Water Monitoring Data for Dichloro-
           ethanes                                                   _  ,
                                                                     b-j.4

  6-7       Example of Monitoring  Data for Dichloroethan-s in
           Ambient Air                                               ,  , .
           Exposure Matrix
                                                                     / -o
  7 2      Respiratory Volumes  for Humans  Engaged  in  Various
          Activities
                                                                     / — 1J

  7-3      Example of Estimated Inhalation Exposure to Trichloro-
          ethylene
                                                                     / — LL

  7-4      Per Capita Consumption of Fishery Products and Food
          Fats and Oils in the U.S., 1976                            7_15

  /-5       Example of Estimated Ingestion Exposure to Di(2-
          ethyl-hexyl)phthalate via selected Food Items '             7-13

 7-6       Example of Ingestion Exposure Estimates  for Cooper
          Based  on Total Diet Studies                     '           7,Q

 7-7       Example of Ingestion Exposure Estimates of  Mercury
          tor a  Specific Subpooulation                               - ^
                                                                    i ~~ ±.\j

 7-3       Example of Estimated Exposure to 1,2-Dichloroethane
          via Drinking Water  Including  Population  Size               -_:>•>.

 7-9       Example of Estimated Maximum  and Typical Human Ex-
          posures  to Trihalomethanes via Drinking Wacer

 7-10      Examples of Estimated Exposures  to Pollutants  bv
         Absorption  through  the Skin

 7-11     Example of Exposure Estimates of Lead for Adults and      7-3?
         Children,  including Estimated Absorbed Dose               7.34

7-12      Example of Laad Levels in Blood in Support of Exposure
         Estimates
                                                                   .' -JO

7-13      Matrix  for Initially Organizing Analvsis of Human-
         health  Effects  Information.                                -  —
                                 xiii

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                         LIST OF TABLES  (Continued^
 Table
 No.
                                                                    Pase
 7-14     Example of Presentation of Mutagenicitv Data—Incidence
          ot Chromosomal Aberrations in Spermatogonia of Phenol-
          Treated Mice                                              7 , ,
                                                                    /-4 /

 7-l:>     Example of Presentation of Teratogenesis Data—Effects
          of Copper Salts in Hamsters                        " "    7.53

 7-16     Tissue Growth Characteristics:   Various Animals           7-59


 8-1       Example of Acute Effects  Data for  Freshwater  Fish—
          Phthalate Esters                                          3_9

 3-2       Example of Chronic/Sub lethal  Effects Data  for Fresh-
          water  Fish—Zinc      i                                    1-iQ

 8-3       Example of Lowest  Reported  Mercury Effects Data  for
          Aquatic Organisms


 8-4      Example of Ranges in Effects Levels for Aquatic Biota—
         Silver                                                     8-15

 8-5      Example of Data on Fish Kills—Phenol                      8-16

 8-6      Example of Consideration of Bioavailability Observed
         in Concentrations of Zinc in Surface Water                 8-13

 9-1      Example of Risk Considerations by Use of Margins of
         Safety—Petitachloropbenol                                  9-12

 9-2      Example of Adverse Effects Summary—Adverse Effects of
         Lead on Man                                                9-13

 9-3      Example of Epidemiological Evidence of  Human Exposure—
         Lead Blood Levels in Man                                   9-14

9-4      Example of Carcinogenicity Data Used  for Risk  Extra-
         polation of 1,2-Dichloroethane                             9-18

9-5      Example of Estimation of  Unit  Carcinogenic  Risk:   Estimat-d
         Number  ot Excess Lifetime  Cancers Per 1,000,000 Population
         Exposed to Different  Levels  of 1,2-Dichloroethane '         9-21
                                xiv

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                       LIST  OF  TABLES  (Continued)
                                                                 Page
9-6     Example of Estimation of Carcinogenic Risk due  to
        Environmental Exposures:  Estimated Ranges of
        Carcinogenic Risk to Humans due to 1,2-Dichloro-
        ethane Exposure for Various Routes of Exposure           9-22

A-l     Factors for Converting Doses Administered in
        Laboratory Animal Studies to Human Equivalent
        Doses                               "                    ,  ,
                                                                A-t
                                XV

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                            ACKNOWLEDGEMENT
     This report: was prepared by Arthur D. Little, Inc. under Contracts
63-01-3857 and 68-01-5949.  The Project Directors for this work were
Dr. George H. Harris and Dr. Alfred E. Wechsler.  Principal contributors
to the development of the methodology described include:  Rosaline C.
Anderson, Sam P. Battista, Marcos Bonazountas, Susan Coons, Charles B.
Cooper, Alan Q. Eschenroeder, Joseph Fiksel, Diane E. Gilbert, Muriel E.
Goyer, Judith C. Harris, Karl D. Loos, Warren J. Lyman, Pamela W.
McNamara, Joanne H. Perwak, Gerald R. Schimke, Kate M. Scow, Andrew
Sivak, and Richard G. Thomas.

     The authors gratefully acknowledge the support and extensive con-
tributions of the staff of the exposure Assessment Section, Monitoring
and Data Support Division, of the Environmental Protection Agency, in°
particular,  Michael W.  Slimak, the Project Director;  Charles Deles and
Michael Callahari were also helpful in guiding our efforts.
                                  xvi

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                                           an
1.0  TECHNICAL SUMMARY
      There is  a continuing need on the part of regulatory agencies
 and_pnvate industry to describe and interpret the impacts of potentially
 coxic_substances in the nation's environment.   In this context,  exposure
 and_risk assessment methods are required to permit a quantitative charac-
 terization of  the sources,  environmental pathways,  and human or  environ-
 mental  effects  ot specific  substances.   In  order to assist in the
 determination  of appropriate regulatory  actions,  the Monitoring  and  Data
 rSf ^!isJ0n.(MDSD>  of  the  Office  of Water Regulations and Standards
 IOWES),  U.S. Environmental  Protection  Agency  (U.S.  EPA) has  developed  an
 an^haTln^iT^10  ^T11 ""  ?erforain§ exposure and  risk assessments,
 and has  applied  this approach to approximately sixty environmental ooilu-
 tants of concern.   Although  the approach  was developed using waterborne
 pollutants  its  elements may be applied  in  a wide variety  of situations
 at varying  levels  of detail.  This report describes  the exposure  and
 ris* assessment  methodology and  provides selected examples of the use
 or the methodology.

     For purposes  of this report, exposure  is defined as the eacouncer
 of a substance in  the environment by human  or animal populations, and
 r^sk is detined as  the probability of an exposed organism sufferin
adverse efrect as  the result of such exposure.

     The scope of an exposure or risk assessment mav be characterized
by a number of key features:

     •  Geographic scale, which  may be  global,  national
        regional, or local.

     •  Pollutant sources, which may  include industrial,
        residential, commercial, and  non-point  sources.

     «   Environmental media,  which may  include  air,  surface
        water,  soil,  groundwater, biota,  or  any combination
        tnereof.

    •   Pollutants  addressed, which may be a specific  substance
        or  a class  of related substances.

    •   Receptor  populations considered, which may include
       humans, animals,  plants,  micro-organisms/or specific
       sub-populations of the above  that are exposed  to
       unusually high pollucant levels.

    •  Adverse effects considered,  which may include acute
       or cnronic health effects as well as  environmental
       efrects.

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     •  Time frame of the assessment, which may be retrospective,
        current or prospective.

     •  Intended use of the assessment, which may be for regulatory,
        scientific, or public information purposes.,

The methodology summarized and described in this report is sufficienr.lv
flexible so that it can be applied with respect to any of the above
definitions of scope.

     An environmental exposure and risk assessment for a chemical substance
generally consists of a series of analytic components, or modules, each
addressing a particular set of relevant information about the substance.
These components are linked together as shown in Figure 1-1, culminating
in an evaluation of risks to humans and other biota due to the presence
of the substance in the environment.  The essential aspects of each
component are as follows:

     •  Initial Considerations—the available information about
        the substance and important environmental issues are
        identified, the scope and focus of the detailed exposure
        and risk assessment are established,  and the  subsequent
        work effort is planned and organized.

     "  Materials Balance—the significant pollutant  sources
        are identified,  and the locations and magnitudes of
        environmental releases are characterized.   This involves
        a systematic examination of the various  activities  which
        produce,  transport,  use,  or consume the  substance,  and
        often requires estimation of environmental loadings  in
        the absence of empirical knowledge.

     •  Monitoring  Data—the concentrations  of the pollutant
        in all  environmental media are  investigated through
        scanning  of field data,  and important  temporal  or
        geographic  variations are noted.   The  monitoring data
        provide a means  of confirming some of  the  materials
        balance and environmental fate  estimates.

     »  .Environmental Pathways and Distribution—the  mechanism
        of pollutant transport and transformation  in  the environ-
        ment are  investigated, leading  to an  assessment of  the
        substance's persistence and its likely partitioning
        among the various environmental compartments.   This  may
        involve the use  of mathematical models to  estimate  the
        distribution of  the  substance in specific  media.

     »  Exposure  of Humans and Other Biota—the  potential exposure
        of humans and other  species is  assessed  through an  in-
        vestigation of the important environmental exposure
        routes  and  the extent or  frequency of  exposure.   For

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                       INITIAL CONSIDERATIONS
  Monitoring
    Data
Materials
 Balance
                Pathways
             & Distribution
                             Health &
                           Environmenta"
                              Effects
                                     Exposure  of
                                       Humans &
                                     Other  Biota
Principal
Information Flow
Selective Data Inputs
                            FIGURE 1-1
                              Risk
                         Considerations
  .MAJOR  COMPONENTS  IN  ENVIRONMENTAL  EXPOSURE  AND RISK  ASSESSMENT
                               1-3

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         humans  this  may address  not  only geographic differences,
         but also  the identification  of specific subpopulations
         that may  have higher  :han average exposure via ingestion,
         inhalation,  or dermal  absorption.

      •   Health  and Environmental Effects—the  potential acute
         and chronic  effects of the substance are evaluated for
         both humans  and other  species.   Data on human  effects
         may come  from either epidemiological or laborator}?-
         studies,  and  will  focus  upon  those effects  most perti-
         nent to the  prevalent  chemical forms and exposure  routes
         of  the  substance in the  environment.   To the extent
         possible, metabolic information  is also taken  into
         account.

      *   Risk Considerations—:he  results of the previous components
         are combined  to yield  an  assessment of  the  potential
         health risks  to humans and other species  due to  the
         presence  of  the substance  in  the environment.   This
         may involve simple comparisons of  toxic  levels  with
         environmental  levels,  or,  as  in  the case  of carcinogenic
         effects, may  require extrapolation of  laboratory animal
         dose-reponse  data using mathematical models.

      Each of  the above  components  is  treated in  detail  in  separate
chapters of  this report.  A comprehensive  discussion is given  of the
means for collecting and interpreting relevant data, formulating and
applying analytic models or techniques and consolidating and presenting
the results.  In addition,  specific examples are  provided  of how these°
methodological components have been used for exposure and  risk assess-
ments of selected priority pollutants.

     An important issue  that is addressed  throughout the report is
data adequacy and the associated  levels of confidence in che exposure
and risk assessment results.  Depending on the accuracy and completeness
of the required data, the results can range from well-defined numerical
estimates to rough qualitative statements.  Moreover,  many of  the tech-
niques utilized to analyze  data,  notably fate modelling and dose-response
extrapolation, involve a number of assumptions  which may not be fully
verifiable.   Therefore, it  is crucial that the  outputs  of the exposure
and risk assessment are properly  qualified in terms of  model and'data
limitations.  Despite such  limitations, a well-organized and scientifically-
documented assessment can be an extremely useful instrument for understanding
pollutant impacts  and guiding regulatory actions.
                                 1-4

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                          2.0  INTRODUCTION
 2.1  BACKGROUND

      The growing concern regarding the nature, distribution, and poten-
 tial effects of toxic and other hazardous chemicals in the nation's en-
 vironment has been reflected in many federal government statutes  rela-
 tions,  and rules.   The Clean Water Act, the Clean Air Act, Resource °
 Conservation and Recovery Act, Toxic Substances Control Act  and Dela-
 tions under these  statutes have addressed these concerns,  and several
 regulatory agencies are charged with implementation of environmental
 management responsibilities (for example, the Environmental Protection
 Agencv.  Consumer Product Safety Commission,  and the Food and Drug
 Aaministration).  Industry organizations and independent research groups have
 also investigated  sources,  pathways,  and effects  of potentially to—'c
 materials and the  exposure for humans and other species to these mortals
 as  part  of a nationwide environmental program.

      Throughout  many  of these  efforts,  there has  been  a focus  OP the
 analysis  of  risks  associated with  the presence  of toxic and hazardous
 chemicals in the environment.   This analysis process,  often referred  to
 as   risrc  assessment   or "exposure  assessment;1  encompasses  many aspects
 including in-depth toxicoiogical experimental  investigations  of health
 effects using  laboratory  animals, environmental monitoring and ^easure-
 ments, and extensive  data collection  and/or  modeling efforts  to determine
 and  predict  tne  concentrations  and fate  of toxic  substances in  the environ-
 men..  This  work is expected to  continue  at  many  levels, both oubliclv
 and  privately  sponsored,  throughout the  foreseeable future.

     The  Monitoring and Data Support Division (MDSD) of the Office of
kater Regulations and Standards  (OWES), U.S. Environmental Protection
Agency (J.S. EPA),  is conducting a program to evaluate  the exposure to
and  risk  or pollutants in the nation's environment.  Part of this P£tor-
is a result ot the  settlement agreement between the Natural Resources
Defense Council  (NRDC) and the Environmental Protection A-enc-  ru S
District  Court, D.C.,  1976)X. Under this agreement, the Monitor-in- and
Data Support Division is evaluating the exposure and risks to human and
non-human species resulting from the occurrence of 129 specific chemicals
in Cl,e water environment (hereafter referred to as the 129  orioritv
pollutants).   On the basis of these evaluations, recommendations for
                                           . Serlemen£
                         ^

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  regulatory actions are prepared  to reduce  the exposure  to and  risks  of
  priority pollutants  in the environment.  In order  to provide a systematic
  and comprehensive evaluation approach, an  integrated risk assessment
  methodology is being developed.  This methodology  is the subject of  the
  report.
 7 7
      TYPES OF EXPOSURE AND RISK ASSESSMENTS
      Exposure and risk assessments vary with respect to their scope and
 use.  The scope of the assessment can be described by several parameters.
 The scale of an assessment is defined by whether global or national,
 regional or local exposure or risks are considered.  An assessment can
 also be characterized by which populations are considered (humans,
 plants, animals, microorganisms, or all environmental species) and whether
 average nationwide risks are evaluated or risks to specific subpopulations
 in specific areas.  The time frame of an assessment can be retrospective,
 current, or prospective.  Finally, an assessment can include evaluation
 of one or many of the potential health or environmental effects associated
 with the presence of a toxic substance in the environment.

      An exposure assessment involves examination of all factors that
 lead to an exposure for human and other species to the pollutant and a
 quantification of that exposure.  A risk assessment includes all the
 elements of an exposure assessment and a qualitative or quantitative
 estimation of the risk to a given population based upon the  exposure
 to and effects of a pollutant (e.g.,  the increased risk of carcinogenicitv
 to the total U.S.  population associated with the environmental presence
 of a chemical).   Throughout this report  we will use the terms "risk
 assessment" and  "exposure assessment" interchangeably,  recognizing that
 risk assessments combine both analysis of exposure and analysis of
 effects to yield an assessment of risk.   (In the published literature.
 these quantitative relationships between risk and exposure are often
 called risk assessments.)

     Risk assessments may have many different uses.  Typical uses include:
development of regulatory approaches,  requirements, or recommendations;
development of environmental standards and/or criteria; establishment
of information, monitoring, or research needs; providing public information,
education, etc.   Table 2-1 characterizes risk assessments in accordance
with all of these general parameters.   The methodology described herein
is called an integrated risk assessment methodology since,  in principle,
the approaches used are applicable to all types of risk and
exposure assessment, independent of scope, depth or other characteristics:
specific portions of the methodology are suitable for independent
studies and assessments.

2.3  REPORT OBJECTIVES AXD GONTZNT

     The objective of this report is to describe an integrated exposure
and risk assessment methodology.   The  methodology is intended to be used
by public and private organizations and individuals who seek guidance on
                                   7-9

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 TABLE 2-1.   PARAMETERS THAT CHARACTERIZE RISK ASSESSMENTS
   Scale
National, regional, local
   Populations
   Considered
Humans, plants, animals, micro-
organisms, all species
   Time  Frame
Retrospective, current, prospective
i   Potential
   Effects
Human Health—carcinogenicity,
chronic functional disorders, etc.

Ecological—habitat, foodchain,
reproductive, etc.
   Intended
   Use
Development of regulations, environ-
mental standards, criteria

Establishment of information or
research needs

Public information/education

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 conducting exposure  and  risk  assessments,  and  to  provide  a foundation
 for  further development  of  the  methodology.  Not  all  portions  of the
 metnodology have  been  considered  in  the  same depth  of'detail.   For
 certain  aspects of  the analysis,  such  as ecological modeling and
 toxicological  research,  unique  methodological  approaches  have  already
 been developed to a  high degree of sophistication.  Therefore,  users'
 may  require additional detail in  some  areas depending  upon the  overall
 purpose,  level of effort, and intended use of  the individual risk
 assessment.  This report presents basic approaches  to  risk assessment
 so tnat  users  may select the most appropriate  segments for each specific
 application.   The general approach is  intended to guide the plannin* and
 conduct  of  specific  exposure or risk analyses  rather than  provide  a°
 detailed  procedure.  Since  this risk assessment methodology was developed
 for  the  EPA to address waterborne priority pollutants, it  is  focused
 on assessment  of exposure and risk where water contamination or
 pollution  is significant.

      Chapter 3 of this report provides an overview of the  risk  assessment
 process, including the goals and objectives of each major  component,
 the  flow of information from one analysis area to another, and  sorae  of
 the major assumptions  and limitations of the process.   The initial steps
 of a  risk or exposure assessment are then discussed.  In Chapters 4
 through 9, approaches  to each component of the risk assessment  process
 are described  in some detail.   The organization of these chapters is
 as follows:

      Chapter 4—Materials Balance—Source Identification and Loading
                Estimation

      Chapter 5—Environmental Pathways and Fate Analysis

      Chapter 6—Monitoring Data and Environmental Distribution

      Chapter 7—Human Exposure and Effects

      Chapter 8—Exposure and Effects—Non-Human Biota

      Chapter 9—Risk Considerations

 In each of  these chapters,  examples are drawn from actual exposure and
 risk  assessments  performed for EPA.   These examples are intended to
 illustrate methods of data analysis or presentation and the reader is
 referred to the full report for specific information regarding each
 pollutant.

     Chapter 10 provides  a bibliography of source materials for the
 conduct of exposure and risk assessment of  environmental pollutants.
This bibliography  is intended  to give the investigator an initial means
of obtaining the  numerous types  of information  needed  to assess exposure
and risk.

     The appendix  discusses sorae of the mathematical details of quanti-
fying risk.

                                  2-4

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            3.0   EXPOSURE AND RISK ASSESSMENTS—AN OVERVIEW
  3.1   OVERVIEW
      The  general  goals  of an environmental  risk or exposure assessment
 are  snown in Table  3-1.   Only some  of these goals  may  actually be realized
 in a specific risK  assessment,  depending upon  the  specific  pollutant,
 the  resources available,  and the  time allowed  for  the  assessment process.

     _ Figure  3-1 shows the major components  of  the  risk assessment procpss
 ihe  initial  considerations component  is  intended to  establish  the scope
 and  focus  of  the  risk assessment, assign priorities  for investigation  of
 specific  environmental pathways,  exposures  or  effects,  and  provide  the
 initial basis  upon which  to  proceed with  the risk  assessment.  The  mate-
 rials balance  component refers to a description  and  quantification  of  the
 tlow of a  pollutant from  its  generation  through  its  initial release into
 the environment.  The environmental pathways and distribution component
 rerers to  analysis of the  pathways traversed bv  the  pollutant in  the en-
vironment, the intermedia  and intramedia transfers that occur, and  the
resultant  environmental distribution, both  spatial and  temporal.
Monitoring data can provide  a major input into the establishment
of the pollutant  distribution.  The exposure assessment component
attempts to characterize the type, size,  location,  and distribution of
populations and subpopulations-human and other biota-exposed to a pol^u-
                                                      -         o a po
     ^ in tne environment and to  establish actual  and potential  exposures
 to tne pollutant  in terms  of extent,  duration, level",  etc.   The  health
 and environmental effects  component  analyzes  the known or  anticipated "
 acute,  chronic, and  other  effects  of  pollutants  on  humans  and  oche/soecfes
 ir possibxe,  it provides a basis for extrapolation  of the  results of '
 laboratory  effects  studies  to real environmental situations  and/or  extrapo-
 lation o, results  of  studies with  laboratory  animals  to human  population
 S^!;..The  riSk  '"^derations component summarizes  previouslv  deviled
 ooou^<      e8tlmate;  l^titativelv, if possible, the risks  to  various
 population  groups, and  places the risks  associated with pollutants   sources
 environmental pathways,  exposure routes, and  health effects  in perspective

 ,,3l ^ fh°Wn in,Fi§ure  3-1, the major flew of information is from mate-
 ant distributer1 mCnit°rin§ data Components  to  environmental pathvavs
 walvie   £-  " components   These data, combined with environmental  fate
 an? J  ?:•   ff    analysis Cf exposure of humans  and other biota.  Exposure
 and healtn effects analyses are combined to yield risk estimates.  Mate
 -ials balance has  indirect inputs to  health and environmental effects *rd
exposure components; similarly,  environmental pathways and  distributor
analysis have indirect inputs to health  and environmental effects.
    r       remainder °f this chapter,  each of the major components  in
    Ioa?-a^STnC Pr°C£SS- ^ dl3CUS3ed brief^>  including focusing on
    goal,  and objectives or chese  steps, some  of  the  approaches  used,  ard
                                   3-1

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TABLE 3-1.  GENERAL GOALS OF ENVIRONMENTAL RISK ASSESSMENT
    Establish pollutant sources,  pathways and
    distribution
    Establish exposure to and effects of pollutants


    Quantify the human health and biotic risks
    Provide information base to derive approaches
    to risk reduction
    Identify data gaps  and research needs
                            3-2

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                               INITIAL
                             CONSIDERATIONS
          MATERIALS
           BALANCE
                      T

                       i ___
         HEALTH AND
       ENVIRONMENTAL
           EFFECTS
        MONITORING
            DATA
             i
                                      ENVIRONMENTAL
                                       PATHWAYS AND
                                        DISTRIBUTION
EXPOSURE OF
HUMANS AND
OTHER BIOTA
                       CONSIDERATIONS
            Note:   Solid lines indicate direct flows of
                   information; dotted lines indicate
                   selective duta inputs.
FlCUKIi  3-|   OVliKVIIW  OF KNV IKONMI'NTAL RISK  ASSKSSMF.N'i

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 the  assumptions  and  limitations  of  the  risk  assessment  approach.   Subse-
 quent  chapters of  this  report  discuss each of  these  components  in more  detail,


 3.2  INITIAL CONSIDERATIONS  IN A RISK ASSESSMENT

     The  initial considerations  of  a risk assessment  include:


     • Establishment of the scope  and  focus of the risk assessment.

     » Identification  of the  subject material to be  considered in
        highest priority and with greatest detail.

     • Development  of  a work  plan  and/or approach for  completing
        the risk assessment.

 This component initiates the risk assessment process  by providing
 a basis for understanding the  requirements of the risk assessment, and
 an organization for  the work conducted  throughout the risk  assessment
 process.  To avoid unnecessary effort and development of data on
 topics of little significance,    it  is essential to carefully define
 the desired goals and outcome of  the specific risk assessment.
 The scope should be  established  in  terms of the parameters described
 earlier—scale, populations considered,  time frame,  potential effects,
 and intended use of  the assessment.

     Once the initial scope and  focus of the risk assessment have been
 defined, the next step is to determine in general terms the type and
 availability of information for  the risk assessment process.  This
 can be accomplished  through brief literature reviews, consultation
 with experts, analysis of recent reviews on particular chemicals,
 etc.   Next,  priority areas of investigation are identified, for
 example, a specific pathway, a  specific  set of health effects, an
 industry of significance,  etc.   Priorities should be  set according
 to the overall requirements of  the risk  assessment and the expectations
 of availability of information.

     Following prioritization of  areas of investigation, the final step
 in the initial considerations is  to develop a work plan for conducting
 the risk assessment.   The  work  plan should estimate  the  effort
devoted to each of the major components, indicate  the major areas
 of information flow  and exchange, and estabiisn a timetable for tne con-
 duct of the risk assessment.

     After several  risk assessments have been performed,  the initial
considerations component will become a "natural process."   Nevertheless, it
 will still be important to identify the  overall goals of the risk assess-
 ment, establish priorities, and develop  a work plan to increase  the
potential  for achieving those goals.

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  3.3   MATERIALS  BALANCE  (ENVIRONMENTAL  LOADING)

       The  objectives  of  the  materials balance  component  are:

       •  To  identify  the  important  (if  not  all)  pollutant  sources

       »  To  identify  the  chemical and physical form  of the  pollutant,
         as  it is  released to  the environment.

       »  To  characterize  the environmental  loading of the pollutant-
         quantities,  geographic locations,  rates, receiving environments.

       •  To  identify  uses and  releases  of the pollutant  leading to dir2Ct
         exposure.

       •  To  achieve a balance between production and uses or releases.

       •  To  establish the confidence or uncertainty of data on releases
         of  the pollutant.

       The materials balance  approach requires a  systematic identificacion
  or sources, estimates of environmental releases, and characterization of
  tne receiving environment.  A comprehensive analysis may be enhanced
  through a checklist  or ordered procedure for examinins  all aspects of
  the processes of generation and release of the pollutant.  Figure 3-2
  shows an example checklist,  indicating a source matrix  and an°environ-
 mental input matrix.  All types of manufacturing processes, transporta-
  tion,  storage, and disposal activities, as well as uses of the pollutant
 or products containing the pollutant should be considered.  Specific
 processes,  uses and releases,  and the environmental compartments
 receiving the release that can lead to  direct exposure potential should
 oe identified.  As a check on the quantification of releases,  the
 degree of closure of the materials  balance (the  relationship  of production
 import,  export,  use,  disposal, and  environmental release data)  is
 estaolished.  The ranges of  uncertainty in environmental releases of
 data for tne pollutant should also be established;  several approaches
 tor this task are discussed  in Section  4.3.

     The materials balance is often a difficult component of the risk
assessment to perform since  there are many production processes, trans-
portacion and storage procedures, and use patterns that  affect re-
leases to the environment.  Processes may not be described, uses mav be
unknown,  and quantitative data on releases may not be available   Thus
in many cases, engineering estimates will have to be made in order to '
describe likely or expected  environmental releases,  The assumptions
and uncertainties associated  with all environmental releases should be
aocumented wherever possible.  Those releases that can result  in ^ir-ct
exposure  ot persons or other  biota to the pollutant should be  hi*hli*hfced
as this information will be directly used in the  environmental  pathwavs
and distribution analysis, as well as the exposure and health er>~e-ts
anaxvses
                                   3-5

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                      SOURCE MATRIX
ENVIRONMENTAL INPUT MATRIX
I
G-\
EXTRACTION
Extraction
Method
drilling
strip inniinij
Type of
Release
routine
accidental
WATER
QUANTIFY

RATE

FORM

LAND

AIR

MANUFACTURING
Manufactuiincj
Processes
chemical
inactions
dujostion
Material
Class
contaminant
by products/
co-products
primary product
1 ype of
Huloase
routine
accidental





                      TRANSPORTATION
Disposal





                                          I-11cnui' •)-•:>   KXAMi-i.r. OK  MATUKIAI.S  HAI.ANCK

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  3.4  MONITORING DATA

       Goals of the monitoring data component of the risk assessment
  are:
       •   To  identify concentrations  of the pollutant in all environ-
          mental  media.

       •   To  determine  the  geographical and temporal  distribution of
          the pollutant  in  these media.
•
         To  identify geographical locations and other  factors  asso-
         ciated with pollutant releases  to the environment and to
         proviae data on possible exposure of humans and other biota.
 cure  nM  "mP°nent °ften be?ins with a comprehensive review of litera-
 ture including access to available computerized environmental data bases
 In? f?i    r dlSCUSSed in Section 6'3-  From these data,  average amb^
 and effluent concentrations in air and water nav be established-  concen-
  rations  in soil,  sludges, plants,  animals,  fish tissues,  foods,'  drink-
          '.f^'-f0^ ^ determi*ed>  evaluated,  and summarized.   It
           nt to  identify,  wherever possible,  the uncertainties  in exper-
                           °f     m°re                      monitor
 indr                                                   ^  <«   moni
 mg  data  include:   uncertainties  in  the  chenical/analytica' orocedures
 useu,  conndence levels,  and  detection limits; uncertainties' in  obtS-
 -ng  representative  samples of the environmental media;  the lack  o* d-t-
 on tne temporal variations in concentrations at different locations?
 uncertainties  in the chemical or physical forms of  the  pollutant?  and
 the  lack  of surriciently  detailed and/or extensive  data!  Despite"  tnte
 limitations, monitoring data  can provide an indication  of the locations
 of pollutant releases to  the  environment, a potential means f ^oca^on&

 conf'rSf £-;rSUre °f ^T13  and °ther bi°ta' and a direct ™*™ of
 fate InsiS? matSrialS  balance and the environmental  pathways and
3-5  ENVIRONMENTAL PATHWAYS AND DISTRIBUTION

     If the environment and the pollutants were "static" and adequate monitor-
ing data were available, materials balance and monitorinz data, combined
witn information on receptor distribution could be used to estimate ex-
posure of tiumans and other biota to pollutants.  However, the environ-
ment is not static-pollutants are transported, undergo transformation
accumulate and degrade— and the actual environmental distribution of a
pollutant is different from that associated directly with environmental
releases.   The environmental fate and pathways component of a risk asse^-
ment is directed at estimating the actual distribution of the pollutant""
in the environment.  Specific goals of environmental fate and oathwavs
component are numerous:                                        .CL^WC..,;,
                                j-/

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      •   To define  environmental compartments of  importance.

      •   To  identify  important  transport  mechanisms;  physical,  biological,
         and  chemical transformation  processes,  and predominant
         chemical  forms  of  the  pollutant.

      •   To summarize transfer  and reaction rates,  controlling
         processes  and lifetimes of the pollutant in  the environment.

      •   To trace pollutant pathways  from sources to  sinks.

      •   To estimate  pollutant  concentrations in different environ-
         mental media and their time dependence.

      •   To compare the  results of the pathways and fate analysis
         with monitoring data.

      •   To establish relationships between releases  to the
         environment  and,exposure.

      A variety of approaches may be used in environmental fate and path-
ways  analysis; qualitative estimates may be based  upon case examples
or environmental scenarios, simple analytical equilibrium or transport
models,  or complex multi-media models.   The materials balance component
provides inputs; evaluation of physical, chemical, and biological fata
processes defines  che persistence of the pollutant in the environment;
and models are used  to  estimate environmental concentrations.  Figure 3-3
shows one approach to pathway analysis.   In utilizing environmental models,
it is important to assess average concentrations in environmental media of
broad geographical distribution, as well as environmental pathways
and resultant concentrations in specific localized areas.   The output
of the fate  and pathways analysis should yield pollucant concentration
distributions in sufficient spatial and temporal detail to allow
estimates of exposure of humans and other biota.

      For many environmental situations,  adequate models do not exist or
are just now under development.  Furthermore,  for new or uncommon chemicals
many  of  the physical, chemical, and biological properties  needed to esti-
mate  transformation rates,  persistence,  and distribution are not avail-
able.   For example,  few models exist  to  predict adequately the distribu-
tion  of pollutants released from the  landfill into ground  water and surface
water.  Models  to estimate  residual concentrations of pollutants in edible
foods resulting from the land disposal  of sludges,  contaminated irrigation
water, pesticide or nutrient application, dry deposition,  are in very
early stages of development.   Therefore,  uncertainties and limitations of
the models should be identifiec.,  and  estimates of pollutant  distribution
based upon materials balance,  fate and  pathways analysis  should be compared
with monitoring data.

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              r
I
vo
                         REVIEW PHYSICAL. CHEMICAL
                     AND BIOLOGICAL CHARACTERISTICS
                               OF POLLUTANT
                          REVIEW FATE PROCESSES
                     CONDUCT SENSITIVITY ANALYSIS
                      TO DETERMINE THE IMPORTANCE
                        OF SOURCE PARAMETERS ON
                      ENVIRONMENTAL DISTRIBUTION
    AGGREGATE LOADING FOR
        DIFFERENT MEDIA
    INITIAL ENVIRONMENTAL
    PARTITIONING; ESTABLISH
      CRITICAL PATHWAYS
     USING SIMPLE MODELS TO
   ESTIMATE RATES OF CHANGE
AND POLLUTANT CONCENTRATIONS
   SUMMARIZE PATHWAYS AND
    DISTRIBUTIONS, COMPARE
    WITH MONITORING DATA
 IDENTIFY EXPOSURE POTENTIAL
                     FIGURK 3-3  SCHEMATIC EXAMPLE OF FATE AND PATHWAYS  ANALYSIS

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 3.6   EXPOSURE OF HUMANS  AND  OTHER BIOTA

      The  analysis of  exposure  of  humans  and  ocher  biotic  population groups
 to pollutants is one  of  the  most  difficult and  critical elements  of the
 risk assessment  process.   In general,  there  is  no  well established  method-
 ology or^body of literature  on exposure.  The combinations  of  exposure
 routes, durations,  extents,  and the numbers  and locations of persons  or
 organisms  exposed may be large and difficult to identify  or characterize.
 Also,  there  is usually a wide  range of estimated and actual exposures
 corresponding to the  nature  and behavior of  the subpopulation  groups.
 However,  estimates  of exposure are essential, since otherwise  the risks
 of the pollutant to various  population groups cannot be ascertained.

      The  principal  goals of  human exposure analysis are:
•
        To determine exposure of the general public to the pollutant in
        terms of pollutant sources, exposure routes, exposure durations
        and frequencies, exposure amounts or extents.

     »  To determine the exposure of the workplace population to the
        pollutant in terms of occupations, types of " facilities or opera-
        tions, the numbers of workers exposed and their characteristics,
        the exposure routes, durations, frequencies, amounts or extents!

     •  To identify specific suspopulation groups in terms of geographic
        location, size, occupation, age, sex, dietary or recreational
        habits, with higher than typical exposures to the pollutant.

     •  Determine the exposure of individuals in these subpopulation
        groups in terms of the aforementioned parameters.

     Similarly, the general goals for exposure ana lv sis of biotic popula-
tions are:


     •  To identify the types, location, and number of biotic species
        exposed to the pollutant.

     •  To determine the exposure routes,  exposure durations and
        frequencies, exposure amounts or extents for the exposed
        species .

     »  To quantify as best possible the exposure of various species
        to the pollutant under consideration.

     Although no  well established exposure methodologies  exist,  a
systematic approach to identifying  and  quantifying exposure is  essential
to the process.   All routes of exposure, i.e. ," ingestion, inhalation"
and ^ dermal absorption,  must be included.  Subpopulations  should  oe  identi
fied  with specific sources  and exposure routes,  for example,  those
                                  3-10

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  populations drinking ground or surface water, urban and  rural population
  groups  those with unique dietary  patterns, using products containin-
  in e« hl                Wh° reSiQ2 near S°UrCeS °r Disposal operations.
  In establishing exposure, it is  important to identify  the characteristics
  of the population exposed; the duration and frequency  of the exposure-
  the range   average and maximum,  of actual or potential exposure for  '
  individuals in the population group that lead to estimates of dailv intake
  for average individuals and those who belong to  special population sub-
       The  inputs to the analysis of exposure come  from the materials  ba^a
  monitoring data tor ambient air and water;  concentrations in foods-  re
  ot patnways analysis;  physiologic data such as  respiratorv rate,  average
  drinking  water intake, etc.; and the use of models or data which  rellte
  average daily intake by different exposure  routes to total bodv bura^
  of the pollutant   It  is  frequently convenient  to display exposure data
  in a  matrix form listing  various routes of  exposure, exposure  parameters
  and estimated or observed intakes for the general population and  those
      Throughout the  analysis of exposure, it is important  to iden-ifv
  data gaps and uncertainties in data.   For example, there will frequen
                ^^^^^^^
                                       1 fata and     toring da
                                                                     e
                         ^
groups  v^h varying sources and quality of drinking water/ since  this
route is one of tne most  significant exposure  routes.  Similarly   dat
                                                                data
     :r wmaec rveys',ocher f°°d'  fish  ^^ «* w
     1  <,              nSeaed t0 SSSeSS exP°su^ through food in-estion
     ingestion can oe  considered a waterborne route of exposu^since
    ™         "                     ~-'
                                                             r.

or aquatic and otbe^- biota  w'nor^     -i ,  -pec^es-   Uata  cm populations
potential concentrates o-: ??« n  f^a     *f CM then be  associ"ed with



and .b-orptlc. assure rootas  should be c

-------
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>      prnrioossv
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-------
 3 •?  EFFECTS ON HUMANS AND OTHER BIOTA

      The  overall goal  of  a human health  effects  analysis  is  t

      rLrTeriZe '^ adVSrSe  health  SffeCtS  in h—  that are   r
      ted  to  occur as a result of exposure  to  a pollutant.  Specif
 or  numan  health  effects analysis are:                      ^pecit

      .  To evaluate acute  and  chronic  health  effects in humans resultin*
        trom exposure  to the  pollutant based  upon occupational or
        accidental exposures  and/or human  epidemiological studies.
        animals, test organisms, tissues, cell cultures, or other biota.


     *  excr-io116 f6 ^StribUCi°n' meCaboli3-> bioaccumulation and
        excre.xon of pollutants in humans and laboratory animals to
        response.      ^ meChanl3mS and relationships between dose and


     •  To estimate  dose-response  relationships  in humans  based  upon
        epidemiological,  accidental human data,  extrapolation of labora-
        tory  animal  data  and  to estimate  "no  effects" levels  in  humans

     Similarly,  the  goals of  analyzing effects on other biota are:
        terrestrial  organisms.
•  To identify and evaluate the acute,  chronic,  and reproductive
   eftects in various species as functions of exposure level.

   To identify factors that influence the  availability of  a pollu-
   ta                                                '       F
       tant to biota.
     The general approach used to perform the human health effects
analysis includes  literature  search,  analysis  of  epidemiological  and

                                3-13

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 between  various  exposure  routes and health  effects.,  and  to  establish  if
 animal models  are  suitable  for extrapolation  to humans.   In undertaking
 these analyses,  it would  be desirable  if data were available on  humans"
 from epidemiologic studies  or information on  accidental  exposures.
 Frequently, however,  these data are not available and  reliance must be
 placed on  extrapolation of  laboratory  animal  data.   For  many chemicals,
 animal data are not available and only  reports of in vitro data exist.
 If no data are available  on a pollutant, inferences' may  be  drawn from
 data on  related  pollutants, using due  caution.  Examination of structure
 activity relationships of various pollutants may provide  information  if
 other data are not available.

     Wherever possible, multiple studies using different  species  of
 laboratory animals should be utilized.  Several methods  of  extrapolating
 dose-response in animals  to dose-response in humans should  be explored,
 and the  results  of these  extrapolations compared with any available epi-
 demiologic or accident data.  Throughout the analysis and extrapolation
 procedures, uncertainties and assumptions used should be  identified and
 quantified.  If  possible, the end result of the human effects analvsis
 should be  the development of quantitative relationships between dose  and
 response of humans and a clear explanation of the data and  rationale
 leading  to these relationships.   In performing a risk assessment, it  may
 not be necessary to examine all types  of health effects if  only certain'
 exposure routes are applicable.   Thus, in the initial considerations  of
 a risk assessment, it will be important to identify major exposure rouces
 so that  the effects analysis can proceed in a direct and straightforward
manner.

     An  analysis of the effects  in non-human species can be accomplished
 through  data collection and preliminary data review,  followed by
 critical data evaluation and summary reporting of the effects.  Data
 should be  collected on both laboratory studies measuring the effects of
 pollutants on various species arid field investigations or case studies
 documenting actual effects of the pollutant in the environment.   Informa-
 tion on  fish-kills, field reproduction studies,  and ocher field data can
 be especially important in verifying effects predicted from laboratory
 studies.    It is important to understand the experimental conditions of
 laboratory tests of effects so that effects parameters such as LD5Q or
LC5Q can be extrapolated to potential field environmental conditions.
 Following preliminary data collection,  a critical  review should be
accomplished.   Lethal and sublethal,  acute and chronic effects should be
examined for fish and aquatic invertebrates in fresh and salt water and
marine and estuarine species.   Important parameters  influencing the results
such as pH, temperature,  water hardness,  type  of bioassay, exposure time,
etc.,  should be considered.   The  effects of different exposure routes
 should be examined.  Toxicity to  terrestrial plant:;  through root  uptake
of pollutants  in the soil and toxicity to  animals  through ingestion of
contaminated biota and water should be examined.   The effects of  the
pollutant on species in the human foodchain should  also be evaluated.
After these data have been evaluated,  they can be  summarized to  iJentifv

-------
sensitive aquatic or terrestrial species,  "no effects" concentrations,
         oTa nr±e"nf  PS'  *** C°nditi°ns which influence environmental
        tor a numoer of important species.
      _ The _ end  result  of the effects  analysis  for both human and non-hunan
  species  is  a  comprehensive summary  of health effects data including un-
  certainties and  ranges in dose-response  relationships,  and applicability
  ot  tne efrects data  to various  potential routes and  to  real -nvircn-   '
  mental situations.
  3.3  RISK CONSIDERATIONS

      The overall goal of the risk considerations component is  to develop
  a qualitative and/or quantitative understanding of  the nature  extent
  and severity of the risks imposed by a pollutant on humans, fish, wild-
  fire and other biota.  The specific goals are:

      •  To estimate the average health risks tc the general human
         population based upon average- exposures and ranges of health effects
         effects associated with the pollutant.

      •  To estimate the extent and severity of health risks associared
         witn the pollutant in specific  human subpopulations that sus'tain
         greater than average risks .
          t, HP-  u   C?! average risks to general populations of fish,
         shellfish,  wildlife,  and other species  based upon average ex-
         posure ana  the range  of effects associated  with the pollutant.

      *   I* *st;jmata the extent  and  severity  of  risks to auboopulations
         of fish,  snellfish, wildlife  and other  species  that'sustain
         nigher than average risks.

      •   To identify sources,  pathways  and causal  factors  associated
         witn  risks  for human  and  other species  in order  to  understand
         possiole  methods for  risk reduction.                 uueraCc.na



      As indicated earlier,  the  combination of exposure  and health
 streets are required to estimate risk to various species.  In evaluat-
 ing tne risks of an environmental pollutant, a single resu^ will U5uallv
 not occur;  ratner  a risk assessment  will describe  a spectrum or risks
 for subpopulations, characterized bv  the tvpe of adverse ef'e-
                        to determine  whether the  acute  or  chronic
 toxic  errects  and  exposures  are  quantifiable,  or whether  qualitative
 measures  must  oe used.  Depending upon  the  degree of quantifi^on
 outcomes  or  tne risk  consideration include:   (1) qualitative indications

-------
 OL possible risks; (2) estimates of risk for hypothetical exposure
 levels; (3) estimates of risks using conservative assumptions on health
 effects, or (4) quantitative assessment of risk for subpopulations v'a
 various exposure routes.

      Several approaches include:  a qualitative comparison of exposure
 leveis with 'no effects" or "lowest effects" levels to indicat- the
 general nature of risks to humans and other biota;  a-semi-quantitative
 analysis using safety factors and application of daily intake and health
 errects data to result in a better defined range of risks for various
 exposures  of humans,  a quantitative risk analvsis to predict, with clear
 identification of the inherent assumptions,  mortality or morbidity
 resulting  from exposure of general and subpopulation'groups  to the
 pollutant.   For example,  the output of the risk consideration component
 may indicate that a margin of safety of  100  or  1000 exists between
 typical average exposures  of humans and  known or extrapolated effects
 levels.  Another possible  output would be  an estimation  of the ran^e
 or  numbers  of  tumors  resulting from exposure of  the general  human popul-
 ation  to^a  known carcinogenic pollutant.   Similarly,  in  terms of  biotic
 risks,  tne  output of  the risk consideration  compbnent  could  include
 either  comparison of  effects  levels  for various  species  with  exposure
 concentrations  or, if  possible,  quantitative  analvsis  of mortal!tv of
 various  aspects  as a  result  of  exposure.

     In summarizing risk considerations,  the  uncertainties present in
 exposure and effects  data  should be addressed.   The basis for the
 effects and exposure  data  should be  carefully examined and confidence
 levels  established, if possible.   Risk quantification  for chronic
 health effects  is often particularly difficult  to express.

     In  order  to  assist  the  regulatory process,  it  is appropriate  to
 analyse  the  risks  associated  with various exposure  routes or  exposure
 scenarios so that  the  benefits  from  environmental regulation  or control
 can be ascertained.
3.9  PRESENTATION OF RISK ASSESSMENTS

     An important element of the risk assessment process is the clear.
thorough, and well-documented presentation of data and results in a
manner which can be understood by scientists, technical experts, regu-
lators, and the public.  Although it is difficult to address the needs
of these varied audiences, attempts should be made to provide information
in the risk assessment report in various levels  of detail,  geared to
different readers.   Frequently it will be necessary to use  secondary
sources of information; but references should be clear and  complete'.
It will be important to present information so that other investigators
can examine the validity of the assumptions,  data, calculations, and
results for future studies. Only if the risk assessment report is pre-
pared in sufficient detail, with sufficient clarity,  will it be most
useful for the purposes intended.
                                3-16

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    4.0  MATERIALS BALANCE—SOURCE IDENTIFICATION AND LOADING ESTIMATION


 4.1  INTRODUCTION

      A thorough understanding of the distribution of a pollutant in the
 environment is essential to determining the likelihood that humans and
 other biota will be exposed to it and the magnitude of the exposure.  In
 principle, the distribution of a pollutant can be established by two
 methods:

       (1)  review, analysis, and interpretation of available
            environmental monitoring data; and

       (2)  development of estimates of sources and loadings
            (discharges or inputs to the environment) of the
            pollutant, coupled with analysis of environmental
            pathways and fate of the pollutant.

 For some well-studied pollutants,  existing monitoring data may  be suf-
 ficient  to provide a  comprehensive  view'of environmental  distribution.
 However,  for  most pollutants,  and  particularly for new chemicals  or
 recently identified pollutants,  extensive monitoring data are not avail-
 able and the  environmental  distribution must  be estimated.   Furthermore,
 environmental monitoring  data  alone are not sufficient to establish the'
 effects  of alternative regulatory  control  strategies  on the potential
 risks  associated  with pollutants since  monitoring  data do not always provide
 positive correlations between  pollutant sources and environmental distri-
 bution.   Since certain chemical  or  product uses may lead  to direct  exposure,
 assessment of the sources,  uses, and environmental loadings of
 a  pollutant is  an important  first step  in  a comprehensive exposure  analysis.

     In  the context of this  exposure analysis  methodology,  the  term
 "materials balance" is defined as a  description of the  flow of  a  pollu-
 tant from  its  generation  through its initial  release  to one of  the  en-
 vironmental compartments  (air, water, land).   Production  and  use, source
 identification, and pollutant loading studies  are  often called materials
 balances,  depending upon  the scope and nature  of the work conducted.  A
 comprehensive materials balance analysis involves  other evaluations as
 well, including the pollutant's transport, storage, common  and uncommon
 uses, and  eventual disposal.

     The concept of a materials balance is illustrated in Figure 4-1
which depicts a pollutant (or product in which a pollutant  is a  contaminant)
at various  stages in its life cycle.  The  pollutant (product) is first
extracted  from the natural environment or  synthesized, and after initial
 transportation and/or storage,  may be further manufactured, processed  or
transported in many more stages than are shown in the figure. Other key
steps in the life cycle are stages  cf use  and  disposal of  the pollutant"
 (product).   The interior of the large box  in the figure represents pro-
cesses  generally conducced in the cultural or  anthropogenic environment

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                          Ground water
    Incineration or
      Effluent
       Spills/ -
       Leaks
Spalls to
  Land
Wastes from mining
operations to
water/air/land
                                                                                                       ENVIRONMENT
                 I     J>" = Transportation Process


                      FIGURE 4-J.  OENERAMXED MATERIALS BALANCE FLOW DIACRAM SHOWING TYPICAL  RELEASES

-------
 At any step within the cultural environment, the pollutant may be released
 to the natural environment (represented by the space outside of the lar*e
 box), e.g., to air, land, water, biota, etc.  The releases mav be planned
 and controlled (e.g.,  a permitted discharge  to  the  air  or  a receiving
 waterbody), or accidental and uncontrolled (e.g., a suill  from
 a rail car or storage tank into the soil or  water,  or'runoff or leachin*
 from abandoned mining sites).  The materials  balance is  more complex when
 natural sources of the pollutant already exist  in the environment,  inde-
 pendent ot human activity.   For completeness,  significant  natural sources
 must be incorporated  in the materials  balance,  although achieving closure
 or oalance of sources,  uses,  and releases  is  far  more difficult when a
 large reservoir already exists in the  environment.

      Product  use may  result in a direct  exposure  of humans  or  other  biota
 ror  example,  lead  in  paint,  cosmetics,  cigarettes,  etc.  In addition
 environmental Releases  may  also  result  in direct  exposure of humans  or
 other biota,  tor example, a  release  in  the workplace.  In other  situations
 the  pollutant  must  be redistributed  in  the environment  (e.g.   into drink-'
 ing  water  or  biota  such as  fish)  prior  to exposure.   Thus a complete
 materials  balance can provide  insights into potential exposure  as weU
 as tne data necessary for estimation of environmental distribution.


 4-2   GOALS OF A MATERIALS BALANCE

     The overall goal of the materials  balance portion of these exposure
analyses is to obtain a complete and quantitative description of the uses
and sources of a pollutant and a characterization of the form and mode  of
should:      P°lluta^ into the environment.   A complete materials balance


      (1)  Describe the types of uses and use  situations, especially fo-
          consumers.                                              J

     (2)   Identify all existing and  potentially  significant  sources  of
          the  pollutant.

     (3)   Identify the  chemical and  physical  form  of the pollutant PS ir
          enters the environment.

     (4)   Characterize  (qualitatively and, where possible, quantirat^el")
          tne  entry  ot the pollutant  into the environment (loadings)  in ''
          terms  of:  amounts, seasonally, geographic  locations, rates
          receiving  environments.

     (5)   Identify uses  and  environmental releases that can lead to dire-
         exposure or receptors.                                    ^-^<^-<.

     (6)  Account for all material produced by achieving a balance between
         the amount proauced naturally, inadvertently and by industry
         anc the amount transformed, contained (unavailable for release)
         stockpiled, and released to the environment.           release),


                                  4-3

-------
      (7)  Establish the confidence and/or uncertainties in the amounts
          of pollutant releases by various sources to the environmental
          compartments.

      Ideally, a materials balance effort would address all potential, as
well  as existing, pollutant sources.  This may not be practicable because
of both data and resource limitations.  Given these limitations, it is
tempting to focus first on the identification of major existing uses,
though sources deemed insignificant on a national scale may be very signi-
ficant in selected areas.  Therefore, care must be taken in limiting the
scope of the analysis.

      A systematic approach to source identification can aid this process;
many  possible  sources must be considered in  order to determine which are
the most important by virtue of their national or local significance or
the opportunity for direct receptor exposure.  The physical and chemical
form  of the pollutant as it enters the environment are important because
these characteristics affect the significance of various environmental
pathways and the resultant distribution.

     The spatial (geographic, source intensity)  and temporal (rate and
frequency of release)  characteristics of the environmental loading must
be considered.   Total pollutant quantities  involved and the character-
istics of the receiving medium are also important.   This information will
ultimately be used to determined the environmental distribution.  Depending
upon the scope of the risk analysis (e.g.,  local, regional or national).
quantification of releases may not be necessary.   Both documented data
and engineering estimates may form the basis for  quantification, when it
is desirable or possible.

     Understanding and delineating the uncertainties  in source and load-
ing estimates,  i.e.,  determining confidence limits,  increases their useful-
ness in the subsequent steps  in environmental risk analysis,  and any
regulatory control recommendations ultimately derived.   Similarly,  achiev-
ing closure of  the materials  balance—i.e.,  equating  all of the production
or input of the pollutant with use,  accumulation, destruction,  or release
of the pollutant to the environment—makes  the subsequent risk
analysis more comprehensive,  substantive, and credible.   The  level to
which these goals and objectives; may be achieved  will depend  upon the a-
availability of data, the nature of the pollutant,  and the effort that can
be devoted to this  portion of the risk analvsis.
4.3  MATERIALS BALANCE METHODS

     There are two major steps in performing a materials balance—the first
is a chorough identification of sources and the second is quantification
of loading/emission rates to the specific receiving compartments of the
environment.   Environmental pathway analysis (see Chapter 5.0)  can then
be used to establish transfers and reactions of the pollutant within ana

-------
 among environmental compartments, which, in turn, determine environ-
 mental concentrations and influence exposure.  Therefore, the data
 developed from the materials balance must be compatible with the require-
 ments of environmental pathway and exposure methodologies.  The major
 challenges in developing a materials balance are the identification
 of sources, assembly of data, and quantification of loadings for
 pollutants that are not reported in the literature or are unknown or un-
 quantified because of the lack of control technology.

      The general approach for a materials balance is shown in the flow
 chart in Figure 4-2.  Key validation issues are:  data completeness
 and uncertainty, materials balance closure, and compatibility with the
 needs of subsequent components of risk assessment.  At many points in
 the analysis, the need for better and/or additional data may arise.
 Judgments regarding the value of higher quality information must be
 made in order to determine whether engineering estimates or continued
 literature review for direct measurements will be required.

      The  first  step  is  to  establish  the  goals  and  scope  of  the materials
 balance effort,  including  the  desired outputs  of  the work  and criteria
 for determining when this  portion of the  risk  analysis has been  completed
 in sufficient detail.  Next, the analysis should be focused on a quali-
 tative description of the  flow of the pollutant within the cultural en-
 vironment and potential releases to the  natural  environment.  This  st-p
 should highlight the unique character of  the pollutant and indicate
 areas requiring extensive  data gathering  and analysis.  The description
 should cover the complete  range of industrial processes that involve
 the pollutant:  extraction, processing, storage, uses of the pollutant
 or product containing the  pollutant, and  all potential disposal  modes.
 The greater the number of  processes, the  greater and more varied are
 the potential opportunities for release to the environment and the more
 complicated and potentially incomplete may be the analysis, due  to
 insufficient data.  Knowledge of major uses of a product, product life-
 times, and disposal processes may become important in establishing
 total environmental releases; these data are likely to be difficult
 to obtain for the entire range of possible products and uses.

     A materials balance matrix,  such as is shown in Table 4-1 for
phthalate esters (Perwak et al. 198la), provides a convenient method for
initially organizing data on pollutant sources and loadings.  Ideally
such a matrix provides a logical  framework for a thorough accounting'of
sources.   The matrix consists of  a source axis for identification of
points of release, and an environmental input axis for estimating and
organizing loading factors or rates for each source.   The matrix includes
the processes relevant to establishing source identification,
e.g., extraction, refining, manufacturing, processing, transporta«-ion
storage,  use, or disposal  (see Table 4-2) and suggests materials
classes and types of releases to  be considered.  It also  pro-
vides a framework for allocating  and aggregating pollutant'releases to
environmental compartments of air,  land,  water ana biota  and listine
data on quantities,  rates and forms of release.
                                 4-3

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                       Establish Materials
                       Balance Goals  and Scope
                Develop  Qualitative  Description  of
                Pollutant  Flow-Outline  Materials
                Balance  Checklist  Framework
Literature
Research
and Data


Identify Pollutant I
Source and Forms
of Pollutant

                Characterize Release of Pollutant:
                to Environmental Compartments
                (Spatial and Temporal)
                                                           Engineering
                                                           Estimates
                Sunmarize Marerials Balance Data
                in Format Compatible with Environ-
                mental Pathways and Fate Analysis
                      Review Materials Balance
                      Completeness, Uncertainty
                            and Closure
Determine Critical
Environmental Loadings
for Pathway Analysis
Identify Major Direct
Exposure Routes
      FIGURE 4-2.   MATERIALS BALANCE METHODOLOGY FLOW CHART

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                            TAliLK 4-1.   t'.XAMPI.K OF SOIIKCIi AND ENVIRONMENTAL  LOADING  MATRIX:   I'HTllAI.ATIi JiSTKKS
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        TABLE  4-2.   SOURCE  IDENTIFICATION FOR MATERIALS BALANCE MATRIX
 Extraction Method

    drilling, dredging,
    strip or pit mining
    wastes (slags, to air,
    water or other)

 Refining Operations

    washing, grinding,
    extraction, distillation,
    physical separation  wastes

 Manufacturing Process

    chemical reaction, cracking,
    digesting, forming  wastes
    (pollutants in form of primary
    product,  by product or co-
    product,  or containment)

 Processing

    extrusion, molding,
    calendaring, drying,
    pressing,  cutting  wastes

Transportation

    loading/unloading, cleaning,
    in transport (volatilization,
    leaks)   by truck, by rail,  by
   plane,  contained  in tank cars,
   drums,  disposal sacks

Consumptive Use

   industrial,  commerical,
   household,  institutional,  or
   agricultural uses in which
   pollutant  is confined/contained,
   applied  (e.g.,  swimming  pool.
   agriculture)  or consumed in products
Naturally or Inadvertently Occurring

   In minerals and soils, in aquatic
   systems, in air, in biota,
   volcanic activity, formation in
   upper atmosphere, natural
   combustion; inadvertent release
   from urban runoff, or use of
   pollutant-bearing products  (e.g.,
   fossil fuels, cement or other)

Disposal Methods

   POTW, septic systems, solid
   waste landfill, contained land-
   fill, incineration,  deep well
   injection,  discharge (treated or
   untreated)  to surface waters
   including lakes, streams or
   ocean,  or deposition in "sealed"
   drums
                                    4-3

-------
      The source and environmental input categories may be further sub-
 divided depending upon the pollutant and the scope of the materials
 balance.  For example, the environmental input may be subdivided bv geo-
 graphy  (e.g., urban versus non-urban), by depth of environmental medium
 (e.g., surface water versus groundwater), or by waterbody type (natural:
 streams, lakes, estuarine or coastal waters; versus manmade:  effluents,
 reservoirs, or sewers).  Deposition on soil may occur as the result of
 aqueous discharges through leaching, adsorption, or sediment transport.
 The relative contributions of these processes may need to be considered
 and the matrix may have to be expanded accordingly.

      Expansion of the matrix to include receptors as they interact
 with receiving media would aid in classifying the relative importance
 of receiving media.  For example, the receptors may be people, fish,
 game, livestock, crops or materials, most of which will have specific
 interaction zones with various classes of emissions (e.g., people
 exposed in the workplace or through product use at home).  Consideration
 of these interactions would be particularly useful in identifying
 direct exposures to a pollutant.

      After^possible  sources,  uses,  and releases  have been  arrayed,  the
 next  step  is  to  develop  and  summarize data  concerning  sources" and  load-
 ings.   The  data  abstracted  from the  open scientific literature and  from
 government  publications  or  contractor reports may  be supplemented  by data
 rrom  industrial  product  literature,  trade journals, or popular periodicals
 and reports.  A  list of  commonly  available  and  reliable data  sources is
 presented  in Chapter 10.

      In  general, one can expect considerable data  gaps and, therefore
 a high degree of uncertainty in the materials balance for ubiquitous
 ana naturally occurring priority pollutants, for pollutants entering a
 variety  of media from numerous sources, and for new chemical pollutants
 or newly recognized toxicants.  Quantitative data may be lackin* for
 various common source categories and  estimation will have to be relied
 upon to till the data gaps.  Estimations made from chemical or industrial
 engineering data will often be based on product levels, emission factors
anticipated spill frequencies, etc.  Different sources of data and -s^'-'
mation procedures will probably be required for each process listed"in"
the materials balance checklist.   Assumptions made in'the estimate should
be clearly stated so that uncertainties can be identified and checked at
a later time, if appropriate.
                                 4-9

-------
     The  structure and approach  to  environmental  fate  analysis  (for
 example,  whether or not computer models are used) will also  help  to
 define  the materials balance matrix.  The appropriate  scales  for  time
 and  geographical regions will become evident by the nature of available
 data or as the available data are reviewed.  Wherever  possible, the
 materials balance data should include identification of  the  physical/
 chemical  state (i.e., phases, chemical complexes, oxidation  state.
 etc.) of  the substance in products  and releases.  In many risk analyses,
 considerable interaction between the environmental pathways  and the
 materials balance components will be required with each  continually
 refined as a result of considerations arising from the other.  Data describing
 the  geographical distribution of sources and loading race characteristics
 are  generated according to the information needs of air  disper-
 sion, stream flow, groundwater, or  lake models used in pathway analysis.

     After data have been summarized, it .is important  to review
 the  results for completeness, close of balance, anc. uncertainty.  Assess-
 ment of completeness is subjective, since additional literature research
 or investigation may lead to new data or estimates.  Judgments will have
 to be made as to whether more effort should be expended  in developing
 additional data on other sources or loadings.   Examination of the degree
 of closure of the materials balance may be useful in making these judg-
 ments.  This will involve comparing all of the pollutant generation steps
 or inputs with pollutant releases or outputs over a. selected  time frame.
 If inputs agree well with outputs,   greater certainty in the completeness
 of the  materials balance has generally been achieved.

     There is some uncertainty associated with most,  if not all, calcula-
 tions and value determinations involved in developing a materials  balance,
 largely due to varying limitations  on monitoring data,  on assumptions
 associated with approximations of pollutant release from different pro-
 cesses  or activities,  and on simulation models.   Sufficient monitoring
 data, which is current and of high quality,  will reduce the magnitude of
 uncertainty associated with a materials balance.  However,  there are
 many components involved in a materials balance and typically good
 monitoring data are available only for a few,  if any.

     Three approaches  are available for evaluating the  uncertainty in
materials balance calculations in order to establish  some degree of
confidence in the results.   The  first is  a parametric approach based  on
a mathematical model linking the input  and output  variables.   In this
approach, ranges  of input values (e.g.,  100-200  kkg/year) are assigned
 (through educated judgment or 'sensitivity analysis) and partial  deriva-
tives are the principal tool in  the parametric  analysis.   The second
approach is  statistical in that  parameters are  statistically  estimated
from the available  data.   Uncertainty associated with a parameter  in
this approach is  expressed in terms of  a  statistical confidence  interval,
that is, the  range  within which  the true  value of  the parameter  is expected
to lie  (e.g.,  100 + 50  kks)  with an assigned degree of  confidence.  As
 there is  uncertainty associated with each parameter  or  dependent
                                4-10

-------
 parameter,  the uncertainties can be  combined by  the method of  error
 propagation to obtain  the confidence of the output variable.
 These two approaches are described in more detail by Serth et  al.  (1978)
 and are currently being studied by the Exposure Assessment GroujT of the
 Office of Health and Environmental Assessment, U.S. EPA.

      A third approach is a qualitative one in which uncertainty is
 assigned to materials balance calculations on the basis of educated
 judgment.   The resulting uncertainty can be defined:  in terms of expected
 ranges;  as the most likely of several values calculated by different
 methods; or as a qualifying statement associated with one approximation
 e.g.,  under x conditions,  it is very likely that pollutant release from'
 this source will be y.

      The outputs  of the materials  balance  are  several:   the source and
 environmental  input matrices,  containing data  on sources and  loadings-
 identification of large or critical environmental loadings and related
 characteristics,  which  can serve as the  basis  for environmental pathway
 scenarios/analyses;  and identification of  major  routes  for direct  expo-
 sure for use in human and  nonhuman  exposure analyses.

 4.4  EXAMPLES  OF MATERIALS BALANCE  OUTPUT

 4.4.1   Introduction

      The examples in this  section are presented  in order to illustrate
 the extent  to  which a materials  balance  for a particular pollutant  can
 be  .ocused  to  characterize  the  predominant sources of the  environmental
 ourden.  As  previously  mentioned, materials balances may quantify  releases
 of  a specie  cnemical  that  result  from its commercial  or inadvertent
 production,  its transportation or use, transportation or use of a
 product  in which  it  is  a component, or natural sources.  The three
 materials balances  discussed below  -  those  for chloroform, copper
 ana pentachlorophenol - are all  different  in their  focus.

     Examples  drawn  from the materials balance section of  the chloroform
 exposure and risk assessment (Perwak e£ al. 1980a) illustrate the
 approach used  to develop meaningful environmental release data  for
 inadvertent sources  since the burden of chloroform in the aquatic
 environment originates primarily from its production during chlorination
 ratner than from commercial releases.  The materials balance
       a^°nS fr°m thS C°Pper exP°sure and risk assessments (Perwak et al .
       address quantification of the environmental burden of an abundlnT
natural material.  The chird example detailed in this section is ^aken
from the pentachlorophenol exposure and risk assessment (Scow et al
where the estimation of environmental releases associated w- th~7he~
ultimate use of materials containing pentachlorophenol was a major
challenge.                                                     J
                                 4-11

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  4.4   EXAMPLES OF MATERIALS BALANCE OUTPUT

  •4.4.2 Chloroform

       Two major reference documents provided the initial conceptual frame-
  wor*  and much of the data necessary to developing a materials balance for
  chlorotorm  (Perwak et al. 1980a); a large study the National Academv of
  Sciences completed in 1978 and a study by a contractor for the U S '
  Environmental Protection Agency, released in draft form in 1980   The
  study by the National Academy of Sciences was completed soon aft-r the
  health hazards of chloroform were initially recognized and hence did not
  have  the advantage of being able to draw upon the substantial bodv of
  research tnat has been done subsequently.  Therefore,  some of the'conclu-
  sions drawn by NAS researchers had to be Devaluated in light of the  more
  recent work.  The very recent U.S. EPA contractor report treated the  "
 commercial processes that generate chloroform in great detail but did
 not contain much information useful for purposes of developing a mat—ials
 balance focused  on the releases to the environment.

      Unlike the  situation with chemical substances that are exclusive^'
 man-made,  the literature concerning chloroform has noted  several signifi-
 cant  sources of  chloroform  releases that originate outside of commercial
 production or consumption of  the chemical.   Since  80-95%  of commerciallv
 produced  chloroform is  consumed  by chemical  reaction as feedstock to- '
 cnlorodifluoromethanes  and  is  not available  for  release to the  env
-------
      Detailed knowledge of industrial processes and the chemical industry
 structure were required in order to generate estimates of source strength.
 For example, calculations based on industry interviews (combined with
 values reported in various symposia)  resulted in an estimate of 12,500 HT
 per year of chloroform produced by the pulp bleaching industry.  The values
 previously reported for this release  ranged from 1 MT per year in -he U S
 to 300,000 MT per year worldwide.   Actually, part of the total release
 occurs during the bleaching process inside the  pulp plant and part
 occurs during treatment of the plant  effluent.   Some data were available
 concerning the chloroform release  during  effluent treatment  stages,  but
 very few data were available for releases during other stages of the
 bleaching process and,  therefore,  the best available approximation had to
 be pieced together from interviews  with industry experts.

      The ultimate measure of success  of a materials balance  study must be
 the degree of closure  obtained between the sources  and use/r«leases  of
 the chemical.   The results  obtained for chloroform  are displayed  in  Table
 4-3 and  Figure 4-3.  As  indicated,  the "unaccounted for"  amount  is equal
 to more  than D0%  of  the  amount  known  to be released to the environment.
 However,  there are also  uncertainties  regarding  the amount of  chloroform
 commercially produced and  the  amount  devoted  to  the major consumotive  use
 (F-22  reedstock).  Therefore,  after laboratory use  and stockpiles are
 taken  into  account,  nearly  all  of the  "unaccounted  for" amount could con-
 ceivably  result from the uncertainty  in the production volumes.

 4.4.3  Copper

     Copper  is one of the more  abundant metals among the 129 priority
 pollutants and as  such has many sources of significant environmental' re-
 leases .  Data are  generally available concerning releases from many of
 these sources for  incorporation into the materials balance fo- copoer
 (Perwak, et al . 1980b) .  A materials balance for copper is shown in
Tables 4-4 and 4-5 and  Figure 4-4.

     Copper is mined and milled in  seven states,  and effluent dischanzes
and solid waste disposal practices  have been monitored in order to determine
the compliance with current environmental  regulations.   With  these da-a

                                        estimated f°r the known produc-'
                e

-------
        TABLE 4-3.   EXAMPLE OF MATERIALS BALANCE OUTPUT INVOLVING
                    INADVERTENT RELEASES—ESTIMATED PRODUCTION AND
                    USE/RELEASES OF CHLOROFORM,  1978
                              Production (kkg)
Commercial Production
  Methyl Chloride Process
  Methane Process
  Loss during Production

Imports

Production as Contaminant
  Vinyl Chloride Monimer
  CH3C1, CH2C12, and CC14

Chiorination of Water
  Cooling Water
  Potable Water
  POTW*
  Swimming Pools

Bleaching of Paper Pulp

Automobile Exhaust

Photodecomposition of Trichloroethylene

Marine Algae
122,500
 36,000
    500
              159,000
   ,679
  2,^60
    912
     91
      3
7,670

2,733



3,466
               12,500

                  965

                  ^50

             (unknown)
                                                            186,78^

-------
      TABLE 4-3.  EXAMPLE OF MATERIALS BALANCE OUTPUT INVOLVING
                  INADVERTENT RELEASES—ESTIMATED PRODUCT AND
                  USE RELEASES OF CHLOROFORM, 1978 (Continued)
                             Uses/Releases (kkg)


 Feedstock for F-22 Production                               142,700

 Exports                                                       7j900

 Destroyed/Retained in Products/Storage                        3,968
   VCM Products                                  2,290
   Pharmaceutical Production                     1,610
   F-ll/F-12 Production (and others)                 47
   CHC13 Production                                 u
   Pesticide Production                              u

 Unaccounted for (including laboratory
   use and stockpiles)                                         \\  ^QQ

                                 Air     Water   Land
 Released  to Environment        19.207     912    496            20,615
   Pulp &  Paper Bleaching       12,100     400~    ^~
   Chlorination of  Water         3,245     221
   Pharmaceutical Extractions    1,525     275    290
   Automobile  Exhaust              965
   CHC13 Production               370      14      6
   Trichloroethylene
   Decomposition                  450     —     —
   VCM Production                  187       2    200
   Transportation & Storage  Loss   177
   F-22  Production                 150
   Pesticides                      38

                                                            186,783


 "'Publicly Owned Treatment Works
source:   Perwak,  J.  et al.   An exposure and risk assessment for trihalo-
         mechanes.   Final Draft Report.  Contract EPA 68-01-3857.
         Washington,  DC:   Monitoring and Data Support Division, Office
         ot  Water Regulations and Standards,  U.S. Environmental Protection
         Agency;  1980.
                                   4-15

-------
                                                                                  Pioduclion
                                                                                17.381 kke
                                                                                     CIlltNllldllllll
                                                                                      Ul Wdlll - 2(1%

                                                                                    Tiichliiioclliyleiu.- - 3%

                                                                                  Aulu Exhaust  b'X.
Produced ti
ConUniiiuiil
 2733 kkg
                           H«la«ed to
                           Eniliumncnl > 20,615 kkg
         FTfillRK  A-3   KXAMPLK OF  GRAPHIC PRESliNTATlON  OF MATERIALS MLANCK
                      OUTPUT—ENVIKONMKNTAL  LOADTNC OF CHLOROFORM, 1978

      k,  eL aJ .  An  exposure and risk assessment, for  tr ilia lomcthanea.  Final Draft  Report.
Contract KPA 68-01-3837.  Washington, DC:   Monitoringand Data  Support Division, Off Lee of
Water Regulations and Standards,  U.S. Environmental  Protection Agency;  1980.

-------
         TABLE 4-4.  EXAMPLE OF COMMERCIAL PRODUCTION AND USE DATA--
                     SUMMARY OF U.S. COPPER SUPPLY AND DEMAND, 1976
 Source/Consumer

 Domestic mine production and
  beneficiation

 Refined Scrap

 Unrefined Scrap

 Imports (refined)

 Imports (ores-concentrates)

 Industry Stocks,  1 January  1976

 Copper  Wire  iMills

 Brass Production

 Other

 Industry Stocks, 31 December 1976

 Total
  Supply
   (MT)
1,287,940

  204,080

  149,660-

  235,810

   99,770

  419,940
Consumption
   (MT)
                                           2,397,200
                    1,349,288

                     567,092

                      39,110

                     441.710

                   2,397,200
Note:  The above figures are for one year (1976).  There is considerable
       statistical variation from year to year; consequently, these do not
       not reflect average values.
Source:   Pervak,  J.  et al.   An exposure and risk assessment  for copper
         Final Draft Report.   Contract  EPA 68-01-3357.   Washington   DC•
         Monitoring  and Data Support  Division,  Offica  of Water~Regulations
         and Standards, U.S.  Environmental Protection  Agencv;  1980
                                    4-17

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   TABLE 4-5,
  Source
EXAMPLE OF MATERIALS BALANCE OUTPUT INVOLVING NATURAL SOURCES-
U.S. ESTIMATED ENVIRONMENTAL RELEASES OF COPPER, 1976

                          Release  (MT/yr)
  Primary Production
  Smelting
  Secondary Production
  Metallic Ore Mining
   & Related Activities
  Copper Wire Mills
  Brass Production
  Iron 5, Steel Production
  Coal Mining**
  Pulp, Paper & Paperboard
  Inorganic  Chemicals
  Steam Electric Industry
  Machinery  Mfgr.
  Electroplating
  Miscellaneous Sources

  Area  Sources:
  Abandoned  Metal  Mines
  Agricultural Applications
  Urban Runoff
  Suspended  Sediment

  Incineration/Refuse

  POTW

  Total

Air
^
2002
A
i
16^' ,2
31,2
171,2
u "
-
-
-
A

—

—
*
—
-
Direct
Aquatic POP,;
13. 4:
Unknown
0.33 73
343
134! 1.4841
15L1 2941
656
1811'2-
no3
43
1743
1511
4003 1,4003
723
9
314.
3,600= *
44 1 34
18,400

Land
1.078.2902
Unknown
&
Unknown
A
421'2
8961'2
_^
«.
_
_
^
9203


_
19.195'*'5'
*
_
               1002
1.9002

9,6 8 O3
                                   3,269"
                                                            1,110,923
  Insignificant
 *These emissions are directly applied to the category in which they are
  reported; however, often during or shortly following release, they enter
  other environmental media.
**Coal combustion  is known to release some copper; insufficient data is
  available to substantiate this quantity.
 *Ihe  total estimated POTW influent  is 11,800 MT/yr (see Table 6).   Thus,
  only a portion of the  sources  have been identified.

 ^Versar,  1978.
  Arthur D. Little Estimate.
  Effluent Guidelines Monitoring Data, analyzed  by Versar,  EPA, 1979.
 *U.S.  Department of Agriculture,  1974.
 5SRI,  1979.
 6E?A,  1974.
 7EPA,  1977.
 3Table 6.
 ^Martin and Mills  (1976).

 Source:   Perwak, et_ al.  An exposure  and risk assessment for copper.
          Final  Draft  Report.  Contract EPA 65-01-2857.  Washington,~DC :
          Monitoring  and Data Support  Division. Office of Water Regulations
          and  Standards,. U.S. Environmenral Protection Agencv;   1980
                                      4-13

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ENVIRONMENTAL
COMPARTMENTS
                                                                       INDUSTRY
                                                                                 Electroplating
                                                                                  (27.200 MT)

                                                                                 Brass Prod.
                                                                               (567,092 MT)
                                                                                        CONSUMPTIVE
                                                                                           RELEASES
           Primary Prndur"on
             (1,281940 MT'
                                                  Copper Wire Mills
                                                   (1,349,288 MT)
      Erosion-
     Suspended
     Sediment
     18.400 MT
                                                                                       Urban Rur.ort
                                                                                         525 MT
                                                     rtefuse
                                                    2.000 MT
                                     Land
                                  1.110.923 MT
                     Air
                   484 MT
 Water
26.909 MT
                                          POTW
                                         3.269 MT
     Copper Use
  Includes smelting
  Industrial releases in which cooper exists as a trace element.  Sources include iron and steel production,
  coal mining, pulp and paperboard manufacture, steam electricity generation, other ore mining, and
  abandoned mines.
 ^POTW effluent includes contributions from human and otner unknown sources.
 Note:   Boundaries between receiving meaium are often undefined and/or changing:  Copper apparently
        released to one compartment can result in another.

               FIGURE 4-4   EXAMPLE OF  GRAPHIC REPRESENTATION OF  MATERIALS  BALANCE
                             OUTPUT—ENVIRONMENTAL LOADING OF COPPER,  1976

       Source:  Perwak jjt_ a_l.   An exposure and risk  assessment  for  conoer.   Final
                 Drart Report.   Contract EPA  c8-OI-3857. Washington,  DC":   Monitoring
                 and  Data  Support  Div..  Office of Water  Regulations  and Standards,
                 >-' . o .  cPA i  1980
                                               4-19

-------
     As with many of the metals, copper occurs in the natural  environ-
ment in combination with other elements.  The release associated with
the mining and milling of these related ores can be assessed from  in-
formation on the nature and scale of production, the level of  sophistica-
tion of recovery and waste treatment technology, the frequency with which
it is applied, and the availability of documentation and monitoring data
on all of the above.  Copper is a significant by-product/co-product of
lead-zinc deposits, occurs in coals, and is released as a consequence of
iron and steel production.  For these major associated production  pro-
cesses, EPA documentation and other published research data were avail-
able to quantify the resulting copper release.

     Copper is consumed in a variety of uses ranging from brass produc-
tion to electroplating to agricultural applications (as an algicide).
The Bureau of Mines annually publishes reports concerning the distribu-
tion of copper and other mined minerals in the U.S. economy.  The  U.S.
Bureau of the Census also publishes import-export data for all inorganic
chemicals.  These sources provide a baseline for estimating releases
associated with the various stages of production and use of copper
(Table 4-4).

     Frequently, information concerning treatment efficiencies or  general
disposal practices can provide :he basis for estimating environmental re-
leases.  For example in the case of brass production,  effluent guidelines
data provided by the U.S. EPA were used to estimate aquatic discharges
of copper from this source; the computed total fell within the realm of
reasonable losses as a percentage of copper consumption in this applica-
tion.  In the case of electroplating, however, estimated releases based
on the available Effluent Guidelines Data (or continuing data source of
the U.S. EPA) exceeded the amount of copper consumed by that industrv.

     This overestimation can be attributed to some of  the underlying
assumptions.  Electroplacers do not always operate on  a regularly scheduled
basis,  nor is their volume of production consistent.  Many are "captive'1
operations contained within a larger industry and produce only to meet
the needs of that parent industry.   Independent electroplaters also use
copper somewhat intermittently since some materials are plated with
nickel, silver, zinc,  or some combination.   Therefore,  a release estimate
for the materials balance based on "averaged" values from limited sampling
of electroplating effluents would be incorrect.   Bureau of Mines staff
and industrialists  familiar with the electroplating industry were consulted
in order to approximate the was^te recovery efficiency  and the maximum
possible percentage of material loss.

     A significant  source of copper to  the environment  is through POTWs
which receive influent from urban runoff,  industrial discharge, and domestic
and commercial  units.   A contractor study performed  for the U.S.  EPA
                                 4-20

-------
 provided removal efficiencies of metals for a "representative" sampling
 of POTW influents and effluents for primary, secondary and advanced
 treatment facilities.  This information was combined with data concern-
 ing total treated effluent from POTWs in the United States and outlying
 territories and an assumed distribution of treatment levels (2% of the
 flow from primary treatment plants, 64% from secondary and nearly 35%
 from advanced).

      A problem  remained,  however,  in identifying the sources  of copper
 in POTWs.  Average residential loading of  42 mg  Cu/day/person was assumed
 on the basis of samplings from sewer systems in  St.  Louis and Cincinnati.
 Residential areas provided roughly one-third of  the copper to POTWs.
 Adequate data on commercial and industrial contributions  were not avail-
 able to permit  a determination of  the source of  the remaining 66% of  the
 copper in POTW  influent.

      Whenever environmental releases are arrayed and totalled,  care has
 to be taken to  avoid  double counting.   The best  example from  the  materials
 balance for copper is the case of  urban runoff.   The volume of  copper
 carried by urban runoff was determined  from stream  samples  of  urban runoff
 to separate storm sewers,  point sources, and unsewered areas.   Possible
 sources of copper released to  the  urban environment  that  would  be re-
 flected in runoff include exposed  construction elements,  transportation
 vehicles,  industrial  applications  (plumbing,  tubing,  valves,  etc.)  and
 settled particulates  from atmospheric  releases (e.g., coal  burning  power
 plants).   This  latter source has already been accounted for as  an air
 release.   Clearly,  though some of  the atmospheric copper  releases  are
 also  included in the  concentrations  in  runoff, separating  these from the
 other components of urban runoff is  very difficult.   Urban  runoff  itself
 may  flow to a POTW, so that  there  is  opportunity  for  triple counting
 the  original releases  to  air.   Often, as was  the  case in'the copper"mate-
 rials  balance,  insufficient data are  available to permit differentiating
 the  relative contributions  of  individual sources  of a pollutant to urban
 runoff  and  POTWs.  Although instances of double  counting cannot always  be
 avoided,  they do result in  uncertainties in  the  analysis and need  to'be
 identified.

 4.4.4  Pentachlorophenol

      Pentachlorophenol (PGP) is commonly used throughout the United States
 as a wood preservative and  its characteristics and applications are fairly
well  known  to this industry.  As a result,  much of the information in-
 cluded  in a materials balance  for this pollutant  came from specialists
 in the  timber and wood products industries, as well as from U.S. EPA
contractor  reports and water quality programs.  In comparison  with mate-
rials balance analyses of others of the 129 prioritv pollutants, the PCP
materials balance  (Scow et al. 1980) was quite simple and  straightforward
due to  the nature of both the manufacture and use of this  compound.

     At the present, PC? is manufactured at three locations in the U.c
as shown in Figure 4-5, by three different  chemical companies".   Each
                                   I-?-!

-------
I
ro
I ->
                                                              v   ^  K#2
                                                               :•• **i »T  t  *\ •
                                                          .  ,.:i:. •>  >:t..;4:-
                                                   «».n.,«.iN,MAl  .; r v(Jv..L?3W..-
        Notes:  1. Baitelte for EPA. 1975

              2. Foieit Service, U.S. Department ot Agricultuie




           FTCURIi  4-5   EXAMPLE OF GliOORAPHlC DISTRIBUTION OF  PRODUCTION SOURCES—LOCATIONS OF

                       PENTCULOROPHENOL MANUFACTURING AND WOOD  TREATMENT PLANTS
       Source:
Scow el al.   An exposure and risk ussessmen.1: for penLnclilorophenol .   FJnal  Draft  Report.

Contract EPA 68-01-3857.  Washington, DC:  Monitoring and Data  Support  Division.  Office

or Water Regulations  and Standards, U.S. Environmental Protection Agency;  1980.

-------
 facility produces POP by the same process during which phenol is
 chlorinated in the presence of a catalyst.  During production, releases
 occur to the air and to water.  Air emissions are limited by a scrubber
 mechanism enabling PCP recovery; incentives for control of atmospheric
 release are economic, as well as regulatory.  At the time of the penta-
 chlorophenol study (1980),  industry production of pentachlorophenol
 was not subjected to regulatory control by the U.S.  EPA;  sampling data
 on aquatic discharges were  not available.   In addition, there were no
 reliable data on the efficiency of the production process with respect
 to aquatic discharge upon which gross annual discharge estimates could
 be based.   Most of the PCP  that is domestically produced  is consumed in
 the U.S.  and there are no identified imports.


       The  wood preserving segment of the  timber industry  consumes more
 PCP than all other users combined.   Though consumption varies from year
 to year, wood preserving consumes roughly  the  same share  of total produc-
 tion each  year:   an estimated 78% (U.S. EPA timber industry)  to  as'high as
 85% to 93% (chemical industry).   When applied  to  wood,  pentachlorophenol
 enhances  toughness,  prevents  discoloration,  and prevents  attack  by wood-
 destroying fungi  and insects.   The  timber  industry is  a relatively mature
 U.S.  industry and as such is  well established  and fairly  well known.   For
 this  reason and because  of  the  industry's  dominating consumption of PC?,
 78% to 93% of manufactured  PCP  can  be fairly well traced  through its  life-
 time  of wood-associated  uses.

       The  timber  industry reports that 415 wood preserving  plants  operated
 by 300 companies  potentially  use  PCP.  These plants  are geographically
 located on Figure 4-5, in a pattern consistent  with  the major timber  re-
 sources of the nation.   Associated  consumption  of PCP by  wood preserving
 planes is  shown in Figure 4-6 as  it  is distributed to six regions  of  the
 U.S.   At this  stage,  wood is  impregnated with PCP and there are  small
 releases to  POTWs and some  to land.   Most  aquatic discharges  from wood pre-
 serving plants occurs  during  a wood  conditioning  process  prior to  applica-
 tion  of PCP.

       Following PCP application, waste streams at 90% of  the  415 wood
 preserving plants are evaporated so that  there  is no aquatic  discharge at all
 ut  tne remaining  10/4, most  use a  stream process cc apply  PCP  treatment and
 treat  their wastewaters with  roughly  81% efficiency resulting in a dis-
 charge of  5.1 MT  of PCP  to  POTWs  (Scow ei  ai. 1980).  The other  plants use
 tne Soulton process  to treat wood and treat  their wastewaters with a 44%
 efficiency  (Scow  et_ al_.  1980) consequently discharging 0.2 MT of PCP to
 POTWs. Only one small wood  treatment plant discharges its waste stream
 directly to surface waters.   This facility operates on an intermittent
 basis  (less than  25 days per year) discharging less than  26.5 kg annuallv.
Most of the PCP released by  wood preserving plants is contained in sludga,
 and these releases were estimated to be 74.5 MT per year on the basis of
 sludge practices and removal efficiencies  (Scow et_ al.  1980).
                                  4-23

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    Nortneait
       l Central
    Southeast
    Soutri Centra!
    Mountain
    Pacific
                         720
                          1080
                                                 4320
                                                            5940
                                   2340
                                             3600
                   J_
                            I
             0     1000     2000     300C

             Total:  18,000 Metric Tons
                                 4000     5000
                                Metric Ton!
                                                         5000
FIGURE 4-6.
                      EXAMPLE OF REGIONAL  DISTRIBUTION OF  USE SOURCES
                      REGIONAL ESTIMATED CONSUMPTION OF  PENTACHLORO-
                      PHENOL  3Y WOOD PRESERVATION PLANTS
Source:
 Scow et  al.   An exposure  and risk assessment for pentachlorophenc]
 Final Draft  Report.  Contract EPA 68-01-3357.   Washington,  DC:
 Monitoring and Data Support  Division, Office of Water  Regulations
 and Standards, U.S. Environmental Protection Agency; 1980.

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     Following the application of PCP to wood at wood preserving plants,
two important factors were identified and quantified:  first, the end
use of materials treated with PCP as illustrated in Figure 4-7; and
second, the regional consumption of PCP-treated wood products as illus-
trated in Figure 4-8.  Although it was not possible to combine these two
factors in a verifiable manner (e.g., identify the number of fence posts
in the North Central states), the end uses of an estimated 84.5% of
pentachlorophenol produced in 1978 were identified.  From this end use,
it was estimated that 344 HT (or 1.9% of PCP used in preserving wood)
are volatilized to the atmosphere based on the known properties of treated
wood and PCP.  It is also possible that PCP runs off the poles, fence
posts and railroad ties when exposed to rainfall and contributes at non-
point releases to groundwater, storm runoff basins, POTWs and surface
streams.  There were insufficient data available, however, to quantify
this release.

     Consumption of the remaining 15.5% of manufactured PCP is known, but
associated releases are generally not as well understood.  Production
of sodium pentachlorophenol (NaPCP) is the second largest consumer, us-
ing 11.7% of annual PCP productipn.  This is a relatively small segment
of the chemical industry whose waste streams are not yet subject to
Federal regulation.  Consequently, insufficient data were available to
estimate releases resulting from production of sodium pentachlorophenol.
NaPCP is used to prevent bacteria growth in water towers, and in the
textile and tanning industries with small associated environmental re-
leases.  It is also an additive to outdoor paints and is believed to be
used in some toy paints manufactured and applied outside of the U.S.
A major concern was identified with respect to NaPCP in paints in this
materials balance, namely that misuse of outdoor paints, (i.e.,  indoors)  and
imported painted toys present a significant potential to human exposure.
However, it was not possible to estimate the magnitude of these exposures.

4.5  SELECTED EXAMPLES FROM MATERIALS BALANCES FOR OTHER POLLUTANTS

     Several components of various materials balance analyses are pre-
sented here as samples of methods typically utilized to estimate re-
leases and as examples of special release situations.   These selections
are discussed in brief and, where appropriate, are accompanied by figures
or tables.

4.5.1  Releases During Transportation

     In the materials balance flow diagram (Figure 4-2)  reference is
made to the transport processes between major points in the pollutant's
life cycle (extraction or synthesis,  manufacture, storage,  use and
disposal)  and subsequent pollutant releases associated  with transporta-
tion.   Relatively few standardized data  are  collected or  maintained
on potential environmental releases during transport largely due to  wide
variations in transport methods and handling practices  bv che carriers,
themselves.   In fact, documentation,  when available,  is  usually  limited

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UumO«f
Fence ?osis
Otnet
          0     1000    2000    3000

          Totai:  18,000 Metre Tons
                                   40CO
                              5000

                             tf 'C Tons
                                                5000
                                                       7000    3000
9000
       10.000
               FIGURE 4-7  EXAMPLE  DF END USE DATA—MATERIALS

                            TREATED  WITH PENTACHLOROPHEXOL,  1978
  Source:
Scow, ejt  al.   An exposure  and risk assessment for pentachlorc-
pnenol.   nnal Draft Report,   Contract EPA 68-01-3857.   Vash^
DC:  Monitoring and Data Support Division,  Office of Wate-     =
           S  and Standards,  U.S.  Environmental Protection Agencv
                                        1-26

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                                        North
                                        Central
                                    5220 Metric Tons
                                                         south-
                                                           east
                                                     2880 Metric Tons
                  Northeast
               4140 Metric Tons
                                          South
                                          Central
                                      2880 Metric Tons
                      West
                 2880 Metric Tons
                                 Total: 18,000 Metric Tons
        FIGURE 4-3  EXAMPLE  OF  REGIONAL CONSUMPTION DATA—U.S.
                     REGIONAL CONSUMPTION OF WOOD  TREATED WITH
                     PENTACHLOROPHENOL, 1978
Source:
Scow, et  al.   An exposure and  risk assessment  for pentachlorophenoi
Final Draft  Report.  Contract  EPA 63-01-3857.   Washington, DC•
Monitoring ana Data Support Division, Office of Water"Regulations
and Standards, U.S. Environmental Protection Agency;  1980.

-------
 to  reported  occurrences  of  accidental  spills  or  leaks.   One  estimation
 method  is  based  on knowledge  of  t,ne  pollutant's  principal  transportation
 mode  and of  the  types  of its  secondary users  (large  or  small,  nature  of
 the operation).

      In a  materials  balance for  phthalate  esters  (Pervak et_  al.  1981a) ,
 it  was  reported  chat the chemicals were  transported  principally  in
 liquid  form  via  unpressured rail tank  car. motor tank car, and,  to  a
 lesser  extent, in small  quantities  (55 gallon drums).

      The amount  of loss  associated with  transportation  (other  than  from
 accidents) was assumed to be  a function  of the size  of  the shipping
 container  and  the remaining amount after the  container  is  "empty."  Most
 esters  are shipped by  rail  tank  cars or  tank  trucks  to  distribution
 points  and sites of  major users.  Some of  the smaller operators  among
 the 8000 compounders of  plastics probably  receive the plasticizers  in
 55-gallon  drums.  Small  operators using  rotational molding,  coating
 processes, and small injection molding processes  could  possibly  obtain a
 major portion  of their plasticizer in  this manner.   Products made with
 these processes  account  for approximately  75,000  kkg of phthalate esters
 per year.

      If it is  assumed  that  80% of this production is accounted for  by 20%
 of  the  companies who are large enough  to purchase in tank car  lots, then
 the remaining  20%, or  15,000  kkg, might  be delivered from  the  manufac-
 turer to the compounder  in  55-gallon drums.   If  between one  cup  and one
 quart of plasticizer remains  in  each empty drum,  then between  0.11% and
 0.46% or between 18  kkg  and 68 kkg could be wasted and  released  to  the
 environment  when the drum is  reconditioned, destroyed,  or stored in a
 manner  that  allows the  remainder to be  released.

      Though  it is unknown what percentage  of  the  phthalate transported
 in  tank cars or  tank trucks remains  after  the material  has been  delivered
 and the tank is  "empty," an estimate of  approximately one-tenth  of  one
 percent remaining was  considered reasonable.  This amount will either be
 cleaned from the tank  prior to loading another commodity or will remain
 in  the  tank  if the vehicle  is in dedicated service.  Information on
 numbers of tank  cars that are dedicated  is unavailable.  For estimating
 purposes,  it was assumed that 0.1% of  the material transported is cleaned
 and flushed  with water.   The  amount  being  transported in tank  cars  and
 tank  trucks  would be approximately 97% of  the total  production.  A
 weighted average of  the  waste from the 3% delivered  in  55-gallon drums
 and the 97%  delivered  in tank cars is  still approximately 0.1%.  For
 calculating  a materials  balance,  it  was  assumed  that 0.1% is lost be-
 cause of transportation-related  causes.

 4.5.2  Publicly  Owned  Treatment  Works

      For some  pollutants, discharge  from publicly owned treatment works
(POTWs)  constitutes one of the largest  direct  releases to surface
 waters. Monitoring  data on flow rates and pollutant concentrations for
                                  4-23

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POTW influents and effluents and on plant efficiency levels have
      -
                                                                     been
  (Fikslf ef af ai98enf %??* ?°" ^ WaS  esti^ted  "?  three  methods
  Ui.Ksei et al. 1981), all based on data compiled  from sampling and
  analysis at 20 POTWs.  One estimation was based on  the  averagf Sfluent





  ""I""?113 "     2° Plan" SUrVeyed "ere "Presantative  of ail plants
  across the country.  An alternate approach used the total  cyanide

    S
           Each  ^      assue    ha    he   oplar0t C7"11d'
  tive of all U.S. POTWs  (Ftksel «  2   198?)!
 concsion »as       f      t     2  otho-.
 to these standards and had suffici^t data oi ,n             operated
 to allow analvsis.  The flo»-wei!hS       ?  U P3""41".'  of Interest
 was 8U for the 2'                    mean °  the rffi"°val a«
 10 primary
used to characterize metals -pmn,  ^   -*•            3  §overnment  survey were
t«rclar7 treatmentZplStsa!S SS^^Sj"^.?  W^f ?  ««ond.ry  and

from POTI^ undergoes primary treatmenc  39/secondarv  ?«-   !  tOt^  tl
secondarv,  and 14% tert-farv ^1-. ^          secondaiy, ia/. advanced

tc remove 88? of zinc  -hiL r %       Advanced secondary  is assumed
86%.               nC' "nile tertla^ treatment is assumed  to remove
                                4-29

-------
     Table 4-6  summarizes  the POTW  zinc budget  based  on  these assump-
 tions and shows  a  total  loading  to  POTWs  of  22,083  MT, of  which 7814 MT
 of  zinc  is discharged by POTWs to the  aquatic environment,  while 14,259
 MT  is discharged to land (Perwak ejt  al_. 1980c) .

 4.5.3  Natural  and Inadvertent Releases^

     There are  several sources of natural inadvertent releases  of pollu-
 tants that contribute potentially large but  usually widely  distributed
 releases to the  environment.  The metals occur  as natural constituents
 of  the earth's crust in  soils and rock formations throughout  the U.S.
 As  soils and rocks are weathered and eroded,  the natural  metals  and  min-
 erals are released to surface streams.  Nickel  concentrations  in soils
 generally range  from 5 mg/kg to  500 mg/kg; the  concentration  in U.S.
 soils averages 30 mg/kg  (McNamara _e_t a_l. 1981).  Other sources  indicate
 that nickel is found at  average  concentrations of 50 mg/kg  in  sedimentary
 rocks, shale, and carbonate rocks.  The average annual total  suspended  load  o
 nickel in the United States is estimated to  be 3.6 billion  MT,  25%  of which
 enters the major streams.  Assuming an average nickel concentration of  30 ma/'
 in  soil, approximately 27,000 MT of nickel is discharged to surface waters' vi,
 this route (McNamara e_t_  al. 1981) .

     Urban runoff also can provide a major contribution  of  pollutants
 to  POTWs and surface waters each year.  Mercury has been found  in urban
 runoff at levels of about 0.2-35 ug/1.  The mean value for  a residential
 area of 720 acres in Rochester, NY was found to be 18.1  ug/1, with  the
 median value for the same set of 10 data points in the range 4-5  ug/1.
 A second study involving less intensive sampling of stormwater  and  com-
 bined sewer runoff in 11 cities across the U.S. (including  Rochester, NY)
 revealed concentrations  ranging  from less than 0.2 ug/1  to  0.6  ug/1.
 The mean and median values for this data set were both equal to  0.3  ug/1.
 (The mercury concentration reported for Rochester in this study was
 0.25 ug/1.)   Lacking further information,  a range of 0.2-20 ug/1  in
 urban runoff was used to show the possible magnitude of the source.
 Thus, for runoff volumes of 17.3 x 1012 1/yr and 3..6 x 1012 1/yr  going
 to  surface waters and POTWs, respectively,  3.5-350 kkg goes  to surface
waters  and 0.8-30 kkg to POTWs each year (Perwak e_t al.  198lb) .

 4.5.4  Releases to the Atmosphere

     Atmospheric releases of a pollutant can be significant and are a
potential pathway to surface waters.  Included among the releases to air
 that are commonly evaluated in a materials balance are releases from
chemical production,  processing or refining,  releases as  a result of
consumptive use and release as  a  byproduct of indirectly  related processes.
Automobile exhausts provide a source of atmospheric emissions which  is
 typically considered as an area source of  release and poses a serious
problem in areas with high  traffic densities.

     Cyanides are one group of  pollutants that has been  detected
automobile exhausts (7iksel e_t  al.  1981) .   The average rate of hydrogen
                                   4-30

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                       TABLE 4-6.  EXAMPLE OF MATERIALS BALANCE FOR PUBLICLY
                                  OWNED TREATMENT WORKS:  ZINC
 Primary treatment

 Secondary

 Advanced secondary

 Tertiary

 Total
                           Treated Flow (MGD)(1'
                      7,525

                     10,137

                      4,731

                      3,812
                     26,205
                                           Zinc Loading  ._.
                                           to POTW (MT)
 6,341

 8,543

 3,987

 3,212
22,083
Treatment
Removal
Efficiency
.17<3>
.81(3)
.88('()
.86(4)
POTW
Discharge
To Sludge
1,078
6,920
3,509
2,762
(MT)
To Water
5,263
1,623
478
450
.65
(overall)
14,269
7,814
                                                                              )  - 0.8427  x flow.
    EI'A 1978 Needs Survey, FKD-2.

 (2)L(MT/yr) = flow (MGD) x 610 (10~6 g/1) x 3.785 (1/gal) x  365  (day/yr)  x  10~6
 (3)
    Flow-weighted mean value calculated from Sverdrup and Parcel Associates data,  Fehruary  1977.
 (4)
    Assume advanced treatment removes Zn proportionately to TSS — estimated  from tables 17,  27,  31  of
    EPA 1978 Needs Survey, FKD-2.
Source:
I'ei-wak, J.  et ill.   An exposure  and  risk assessment for zinc.   Final Draft Report.  Contract
EPA 68-01-3857.   Washington,  DC:  Monitoring and  Data  Support Division, Office of Water
Regulations and  Standards,  U.S.  Environmental Protection Agency;  1980.

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cyanide emissions has been reported to be 12 mg/mile.  A fleet
composite emission factor was estimated for hydrocarbons in automobile
exhaust:  8 g/mile in 1976.  The resultant CN/HC emission ratio (1.5 x
10~3) multiplied by the total annual hydrocarbon emissions of
12 x 10b kkg/year yields an estimate of HCN emissions of 18,000 kkg/year.
Applying the CN/HC emission ratio to estimates of exhaust emissions
compiled by U.S. EPA, the largest cyanide emissions from automobile
exhausts would occur in areas of the highest traffic density, such as
California (1500 kkg CN/year) or the combined states of New York and
New Jersey (1500 kkg tons CN/year) (Fiksel et al. 1981).
                                '  -i O
                                •4-jZ

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                             REFERENCES
 Fiksel, J.; Cooper, C.; Eschenroeder,  A.;  Goyer,  M.;  Perwak,  J.;  Scow,  K.;
 Thomas, R.; Tucker, W.; Wood,  M.   An exposure and risk assessment for
 cyanide.  Final Draft Report.   Contracts EPA 68-01-3857,  68-01-5949.
 Washington, DC:  Monitoring and Data Support Division,  Office of  Water
 Regulations and Standards,  U.S. Environmental Protection  Agency;  1981.

 McNamara,  P.;  Byrne,  M.;  Goodwin,  B.;  Scow.  K.; Steber, W.; Thomas, R.;
 Wood,  M. :  Wendt,  S.;  Cruse, P.   An exposure  and risk  assessment for
 nickel.  Final Draft  Report.   Contracts  EPA  68-01-5949  and  68-01-6017.
 Washington,  DC:  Monitoring and Data Support Division,  Office of  Water
 Regulations and Standards,  U.S. Environmental Protection  Agency;  1981.

 Perwak, J.; Goyer,  M.;  Harris,  J.; Schimke,  G.; Scow,  K.; Wallace, D.
 An exposure and risk  assessment for trihalomethanes.  Contract EPA 68-01-
 3857.   Washington,  DC:  Monitoring and Data  Support Division,  Office  of
 Water  Regulations and Standards, U.S.  Environmental Protection Agency;  1980a

 Perwak, J.;  Bysshe, S.; Goyer,  M.; Nelken, L.; Scow,  K. ;  Walker,  P.;
 Wallace, D.  An exposure  and risk  assessment for  copper.  Final Draft
 Report.  Contract EPA 68-01-3857.   Washington, DC:  Monitoring and Data
 Support Division,  Office  of Water  Regulations  and Standards,  U.S.
 Environmental  Protection  Agency; 1980b.

 Perwak, J.;  Goyer,  M.;  Nelken,  L.;  Schimke,  G.; Scow, K.; Walker,  P.;
 Wallace, D.  An exposure  and risk  assessment for  zinc.  Final Draft
 Report. Contract  EPA 68-01-3857.   Washington, DC:  Monitoring and Data
 Support Division, Office  of Water  Regulations and Standards, U.S.
 Environmental  Protection  Agency; 1980c.

 Perwak, J.;  Goyer, M.;  Schimke, G.; Eschenroeder,  A.; Fiksel,  J.;
 Scow,  K.;  Wallace, D.   An exposure  and risk  assessment for phthalate
 esters.  Final  Draft  Report.  Contracts EPA  68-01-3857, 68-01-5949.
 Washington,  DC:  Monitoring and Data Support Division, Office  of  Water
 Regulations  and Standards,  U.S. Environmental Protection Agency;  1981a.

Perwak, J.; Goyer, M.; Nelken,  L.;  Scow,  K.;  Wald, M.;  Wallace. D.  An
exposure and risk assessment for mercury.  Final Draft Report.  Contracts
EPA 68-01-3857, 68-01-5949.   Washington,  DC:   Monitoring and Data  Su"Pnort
Division, Office of Water  Regulations and Standards, U.S.  Environmental
Protection Agency; 1981b.
                                4-33

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Scow, K.; Cover, M.;  Perwak,  J.;  Payne,  E.;  Thomas,  R.;  Wallace,  D.;
Walker, P.; Wood, M.   An exposure and risk  assessment for  pentachloro-
phenol.  Final Draft  Report.   Contract EPA  63-01-3857.   Washington,  DC:
Monitoring and Data  Support Division, Office of Water Regulations and
Standards, U.S. Environmental Protection Agency;  1980.

Serth, R.W.; Hughes,  T.W.;  Opferkuch, R.  E.;  Einautis,  E.G.   Source
assessment:  Analysis of uncertainty principles and  applications.  EPA-
600/2-78-004u.  U.S.  Environmental Protection Agency; 1978.
                                a— j4

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                 5.0  ENVIRONMENTAL PATHWAYS  AND FATE ANALYSIS
 5.1   INTRODUCTION

      The  results of  the materials balance  analysis will  normally  provide
 important  information  on  pollutants  that enter  the environment; the
 amounts,  types, forms, rates, and locations  (both in  terms  of  region  and
 specific  receiving medium) of environmental  releases; and indications  of
 direct exposure routes associated with  the release of pollutants  to the
 environment.  If the environment and chemicals were static, materials
 balances,  combined with information on  receptor distribution,  could be
 used  to estimate exposure of humans and other biota to environmental
 pollutants.  In most cases, the environment  is not static but  is  dynamic
 in the sense that pollutants may be transported, undergo physical, biol-
 ogical and chemical transformations, accumulate or disappear,  resulting
 in an environmental distribution quite different from that associated"'
 with  the initial environmental release.  For example, Figure 5-1
 summarizes the major environmental transformations and transfers  of
 trichloroethylene and illustrates the dynamic nature of the chemical's
 behavior following its release into environmental media  (Thomas ~t al
 1981)   Therefore  the environmental pathways and fate Processes~f~he oollutant
must be considered before one can determine with a reasonable decree of '
confidence the pollutant's chemical form and environmental concentrations
 to wnicn receptors might be exposed.

     In analyzing environmental pathways and fate,  the following types
of questions are important:

     •  Do the pollutants  remain in the  environmental  media  (air,  water,
        land,  biota)  in which they  are  initially released or are there
        intermedia  transfers?

     •  By what mechanisms are the  environmental concentrations of the
        pollutant  decreased  or increased,  e.g.,  biodegradation  or  intra-
        and intermedia  transfer?

     • What  are the  controlling external influences on intermedia
       and intramedia  transfer?

     • What  are the  rates of  these  transfers or reaction mechanisms?

     • Are there any potential degradation products of concern with
       respect  to environmental or health  risks?

     •  Is  a steady state pollutant concentration distribution in  the
       environment achieved?  Is the total environmental load increas-
       ing or decreasing?  What are the environmental dynamics'
                                   5-1

-------
Ui
I J
                      from
                     Sotuces
             (bjckijtuund cuncuntrdiion
                                                                                          - Photochemical Duyiadation
                                                                                         ,* '/iday - 2»laysl
                    Lejching to Deep Suilk
                     and Gruurtdwalar
         (liont dump*,,
            t'is, ulc )
                                                                                                                           Sorpuon/
                                                                                                                           Oesutpiion
                                                                                                                           Minor
                    Aquiler (loriQ residence lime)
       Source:
                                      FICURE 5-1   EXAMl't.E OF  ENVIRONMENTAL  PATHWAYS AND  FATE
                                                    ANAI.YSIS— MAJOR PATHWAYS  OF TRLCH1.0ROET11YLENR
                                               wM                         f"r  flchloroethylene.   Final  Draft Report.
                       at  on  and  Standard-  ul   r  "'       MV»Icori"8 a"d  »«ta  Support  Division, Office of' Water
                       at ions and  .Standards, U.S.  Environmental  Protection Agency;  1981.

-------
      •  What is the anticipated spatial and temporal distribution of the
         pollutant:  in the environment, in different media, among different
         types or forms of the pollutant, for different geographical areas,
         for different time frames?  Are these distributions confirmed bv
         monitoring data?

      Answers to these types of questions will provide information on the
 exposure of different receptors that come in contact with various environ-
 mental media, particularly if these receptors play a role in the trans-
 port,  reaction or distribution of the pollutant  (e.g.,  biodegradation.
 uptake by plants,  etc.) or are associated  with a particular medium that
 accumulates the pollutant (e.g.,  persons who  ingest contaminated fish
 tissue).

     Monitoring data  have often been considered  as a substitute  for  en-
 vironmental pathways  and  fate analysis   since monitoring  data  directlv
 provide  the environmental distribution  of  pollutants.   Ideally,  an en-
 vironmental pathway and fate  analysis should  be  conducted  in addition to
 review of  monitoring  data for several reasons:

      (1)   For many pollutants,  particularly organic  and new chemicals,
           monitoring data are limited,  sporadic, and/or of questionable
           reliability.

      (2)   Analysis of available monitoring data does not enable  the
           estimation of environmental concentration distributions in
           media or geographic  locations  for which  monitoring data are
           not  available.

     (3)   Analysis of monitoring data does not provide information on
           how  and where physical, chemical and biological processes in-
           fluence the environmental distribution of a pollutant.

     (4)  Analysis of the  effects of different pollutant control  options
           requires some knowledge of the relationship between environ-
          mental loadings  and concentration distributions-, thi«
           information is provided by fate models  rather than by monitor-
          ing data.

  _   Monitoring data, when available, can be a direct source of informa-
 tion for exposure analysis and can be used to calibrate (or e^tranolate
 trom) models  used to estimate environmental distributions.  However  in
most exposure analyses, it will be important to evaluate pathways and
 fate data as wexl as aid  in exposure determinations and in the  d-velop-
ment of regulatory recommendations.

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5.2  GOALS OF ENVIRONMENTAL PATHWAY AND FATE ANALYSIS

     The overall goal of environmental pathway and fate analysis is to
establish the distribution of pollutants—both spatially and temporally—
in all environmental media.  This general goal can be divided into a
number of specific objectives as follows:

     (1)  Define environmental media or compartments of importance to
          the environmental behavior of the pollutant, including sub-
          compartments such as soil layers, aerobic or anaerobic zones,
          where necessary.

     (2)  Identify important mechanisms for transport and physical,
          biological and chemical change (pathways) of the pollutant
          within and among environmental media.

     (3)  Summarize and/or develop data on the rates of these transfer
          and reaction processes, determine the processes that control
          environmental fate and distribution, and identify predominant
          chemical forms or degradation products in various media.

     (4)  Estimate "lifetimes" or half-lives of pollutants in the environ-
          ment

     (5)  Using materials balance/environmental loading estimates as in-
          puts, trace the environmental pathways of pollutants from their
          sources to their sinks or ultimate distribution in the environ-
          ment.

     (6)  Estimate average or representative pollutant concentrations
          and their time dependence in specific environmental media.

     (7)  Estimate concentrations and their time dependence in specific
          geographical locations—e.g., river basins, streams, rain, air
          sheds, etc.

     (3)  Use monitoring data ;o compare (and to improve) the results of
          environmental pathways and fate analysis wherever possible.

     (9)  Using pathways and environmental fate analysis, develop informa-
          tion for use in exposure analysis, and provide a basis for
          estimating quantitative relationships between environmental
          releases and exposure.

     Ideally, a pathways and fate analysis traces all of the environmental
releases of pollutants from specific sources through the environmental
pathways that occur, and combines the resultant contributions of eacb
release and transfer Co obtain the spatial  and temporal  distri-
bution of the pollutant in the environment.  A careful accounting of
pollutant inputs, inter- and intramedia transfers, -and transformation/
accumulation/degradation processes, should reveal the variation in
                                 5-4

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 distribution of the pollutant over  time.  This might be accomplished by
 using a simple partitioning model for a rough estimate, a complex
 environmental model or similar analytical techniques.  Large-scale multi-
 media models exist; however, they have been designed either for specific
 pollutants or for specific environmental compartments and geographical
 areas.   These large models require extensive and elaborate calibration
 procedures.  Furthermore, the set of necessary input data—loading rates,
 transport and transformation rates,  and other characteristics of the
 pollutant—is difficult to obtain or the data are not reliable enough
 for the results to be credible.   Resource allocations further constrain
 such efforts.   As  a matter of necessity,  environmental fate and pathway
 analyses often are fragmentary and incomplete,  focus on only a few major
 pathways,  and do  not give complete distributions of concentrations of
 the pollutant.  To be useful in exposure  analyses,  environmental fate
 and pathways analysis should at  a minimum:

      •   distinguish key pathways  from insignificant ones;

      •   focus  on key pathways  and on media where the amount  or concentra-
         tion of pollutant is large and  where exposure of  humans and
         other  biota is  expected;

      •   estimate a probable  range of pollutant concentrations  in differ-
         ent environmental media,  with time and space resolution appro-
         priate  to  pollutant  sources  and receptor  exposures of  concern;

      •   provide estimates  of uncertainties that  can be  carried  through
         the exposure  or risk analysis.

      The outputs of  the pathways  and  fate analysis  will be greatly con-
 strained fay the amount of  information available concerning the  physical,
 chemical, and biological  characteristics of  the pollutant; the  types,
 nature, and  location of the pollutant sources; the  existence of models
 or calculational approaches available to estimate' the concentrations; and
 the resources committed to the analysis.

      In keeping with  the  goals of exposure and risk  assessments within the
 Office of Water Regulations and Standards, the methodology focuses on
 water-related pathways and fate analysis.  Non-water-related pathways
 should, of  course, be considered because of the interrelations among
 environmental media, and  in order to  obtain a perspective on total exposure

 5.3  ENVIRONMENTAL PATHWAY AND FATE ANALYSIS METHODS

     Three general methods useful for environmental pathway and fate
analysis are described in this section.   The methods have similar goals
several common steps, and may use some of the same data and information.
Eacn one, however,  has a different focus.   The choice of approach wilj
depend upon the nature of the pollutant,  the  scope of the exposure
analysis, and the  availability of data.   In general, portions of mo-*
than one approach  may be used and the results integrated in order to

-------
 develop  a  more  complete  understanding  of  the  environmental  pathways  and
 fate  of  a  pollutant.

 5.3.1 Environmental  Scenario/Case  Example Method

      This  approach will  provide a qualitative assessment of  pathways  and
 fate  mechanisms,  supplemented by semi-quantitative  information  on  pollu-
 tant  distribution where  sufficient  depth  of analysis of specific case
 examples is  gained from  literature  sources.   It begins with  a brief
 review of  materials balance and environmental loading data  to identify
 relevant scenarios or case examples  for a particular pollutant  (see
 Figure 5-2  for  steps  in  process).   Each major source category is iden-
 tified and  hypotheses are developed  concerning pollutant fate,  beginning
 with  the source and proceeding to an ultimate sink  or environmental
 distribution.

      For example, considering agricultural application as a  major  source
 of a  substance used as an herbicide, one would indicate diagrammatically
 the likely  pathways and  fate processes beginning with the application
 and including:  soil adsorption/desorption, chemical decomposition, bio-
 degradation  in  the soil, volatilization, runoff and leaching into  local
 waterways,   uptake by plants or animals and distribution along the  food
 chain (i.e., all major known fata mechanisms).  Exposure routes suggested
 by this scenario  include ingestion through food and drinking water (both
 humans and non-humans) and possioly skin absorption through contact with
 polluted water.  A scenario such as this describes  the likely pathways  to
 be examined  further or validated in subsequent steps.

      The second step is  to assemble and review available data to aid in
 evaluation of the pathway and distribution hypotheses.   Literature data
 from both laboratory and field studies, as well as measured concentrations
 in the environment would be reviewed for mechanisms and rates of transport
 or chemical and biological transformation.  Data on the physical,  chemical,
 and biological characteristics relevant to determining the pollutant's
 fate  in the environment would also be reviewed.   Using herbicide applica-
 tion again as an example, one would review laboratory  and field data on
 plant uptake, soil adsorption, concentrations  found in soils and water,
 the rates of transfer from soils to ground (through leaching) or surface
water (through runoff) or to air,  as well as  data on speciation, photolysis,
biodagradation,  hydrolysis,  and other transformation processes.   These data
 can provide quantification or at least support comparison of the processes
or major pathways involved.

     When no data are available,  one of several  estimation techniques mav
be used to  provide a rough idea of the significance of particular  proper-
 ties of a chemical in its environmental fate.   For example,  Lvman  et  al.
 (1982) have compiled methods for estimating a  number of physical,  chemical
and biological properties of organic chemicals in one  handbook;  these
methods will be computerized in the near future.

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Develop scenarios
and hypotheses for
environmental path-
ways beginning
with materials
balance outputs
                             Review and analyze data
                             from "case examples"  of
                             studies of pathways and
                             distribution of pollu-
                             tant
                             Review and analyze physical
                             chemical and biological
                             properties of the pollu-
                             tant, pertinent laboratory
                             or field tests on mobility
                             and stability in the en-
                             vironment
Draw general
and specific
conclusions on
major scenarios
and hypotheses
                         Associate environmental  distribu-
                         tion vith sources,  and extrapolate
                         if possible from loading estimates
                         to environmental distribution
             FIGURE  5-2  DIAGRAM  OF ENVIRONMENTAL SCENARIO APPROACH
                          TO PATHWAYS AND FATE  ANALYSIS
                                     5-7

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     The third step is to draw both general and specific conclusions
concerning the key factors influencing the fate of the pollutant, how
the pollutant is partitioned in the environment, likely" concentrations
in each compartment, and so forth.  General conclusions may indicate
that certain sources are associated with higher water concentrations in
a particular habitat than others,  or that one transformation process is
more important than others in the ultimate fate of a substance.  Specific
conclusions may be drawn from selected subjects described in the liter-
ature, and may yield either semi-quantitative relationships between
loading rates and environmental concentrations, or specific data relating
to the rates of typical processes.

     The final step is to relate the specific sources and loadings given
in the materials balance to the pollutant's environmental distribution.
This step can indicate where likely exposure to the pollutant may occur
and give some idea of how exposure may change as a function of future
control strategies.   In a sense,  this final step involves reexamination
of the scenarios developed in  the  beginning,  attempting to  quantify them
and show the relationships between the sources and distribution of' the
pollutant and resultant exposure.

     The environmental scenario method seems most appropriate  in the
following situations:

      (1)  Sources of the pollutant are relatively well known and major
          sources can be distinguished from minor ones in terms of the
          quantity released to the environment and its relationship to
          potential exposure.

      (2)  The pollutant is well-known in the sense that field  and labora-
          tory studies  exist, data on the chemical, phvsical  and biol-
          ogical characteristics of the pollutant are'available, and the
          behavior of the pollutant in the environment has, at least, been
          addressed by others.

     (3)  Monitoring data for  the  pollutant are available,  so  that
          measured data rather than estimates can be used in forecasting
          exposure.  The fate  and  pathway analysis in this  case is more'
          important for linking sources to environmental pathwavs and
          spatial and temporal distribution rather than to  estimate con-
          centrations.

     (4)  Large-scale models describing the pollutant pathways are either
          not available,  not useful,  overly complex,  or too general or
          gross in scale for application  given the resources available.
          Additionally,  the availability  of other  data  described  above
          may make the  use of  complex estimation techniques  unnecessary.
                                   5-6

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       5'3'2  Critical Pathway/Distribution Estimation Method

       This approach is focused on identifying the critical pollutant
  pathways  that  are most influential in determining distribution of the
  pollutant and  the resultant concentrations in the environment.   The
  steps  involved are shown diagrammatically in Figure 5-3 and described
  briefly below.

       This approach also  begins with  the  results  of the  materials  balance
  analysis.  However,  rather  than  scenarios  of environmental  pathways re-
  lated  to  particular  production or  use  patterns,  aggregate loadin*'rates
  (temporal or spatial  combinations) for different media  are  first°devel-
  oped,  eitner on a  nationwide  basis or  for  specific regions  with identified
  environmental  loading patterns.  For example,  the total  annual loading
  from direct and indirect  releases  to air,  water,  soil,  and  occasionally
  biota, etc., are determined from the materials balance  results; estimates
  are then  made of  the  sizes of receiving media, e.g., volume of water, air
  or soil receiving  the  total loading.   If possible,  these  estimates  mav be
  made tor  regional  or  other smaller scale geographical locations,  to  focus
  on areas  of concern.   General environmental  characteristics of the  re-
  ceiving media important to the pollutant's distribution are also  estimated
  e.g.,  pH,  soil moisture content,  etc.

  _   Second,  data on  the physical,  chemical and biological  characteristics
 or the pollutant are reviewed.  Pertinent data may include molecular vei*h«-
 aqueous solubility, vapor pressure, octanol/wacer partition coeffirient " "
 biodegradacion rates, chemical reaction rates, etc.  These data are uspd to
 provide insight into important transformation processes  that remove the
 polxutant  and/or convert it  to other products or potential contaminants.
 -roaacts  identified may also be  considered for toxicity  and  further ^rans-
 rormation.  (Time  and resources  generally prohibit full  consideration of
 these  products  in  an exposure  assessment.)

     Third, pathways  and processes  that result in transfer of  the  pollutant
 trom one medium to  another are evaluated  in order to identify  the  critical
 transter pathways  and estimate the  relative rates of the transfer  processes.
 For example,  for a  pollutant initially  released  to water,  vaporization and
 sedimentation might be considered in order  to determine  whether and  how
 rapidly the pollutant  is  transferred  to the air or soil  media.  Basicallv
 this analysis is a  simple  partitioning  study,  to  determine if  the  oollutant
 tends  to remain in  the initial receiving medium or is transferred  r0  others
 xn some cases, all  of  the  pollutant may be  rapidly redistributed to  other
media; wnile in others, a  slowly established  equilibrium distribution  may
be indicated.

     Following an initial  determination of  the partitioning, the next  step
is a more  detailed  examination of the pollutant fate in the  media  tha«- are
ot most interest, e.g., those media or subcompartments into which  the
poUutants are likely  to be partitioned.  Each major fate process  is re-
viewed, using rate and equilibrium relationships and estimation techniques
.rom tne literature, pollutant specific data  (e.g., rate  constants) from
laboratory or rield studies,  model ecosvstem results, etc.  Tvt>ica> nro-
casses  to  oe examined include:
                                   3-9

-------
                         Keviuw physical, chemical
                         and  biological character-
                         istics of pollutant that
                         Influence late and pathways
          Using  materials
          balance  Lesult.s,
          aggiegale  load-
          ing  for  dlflerent
          im-dia, on  national
          and  situ I IL- r  bra le
          where  pos^ idle
O
tlxamlne and quan-
ti fy, where pos
slble, initial
parti tinning
among environ-
mental mediu;
establish critical
pathways for
t rans f«r
II-
cal
	

— -


Review tale pro-
cesses In each
media to estab-
lish key deler-
mlnanls of con-
centrations and
ills U 1 but I on


—


Using simple
mode 1 y and ra r e
01 tujui i ibr Linn
re lat ioitbhi pt» ,
et>l iiiule rules
of change, and
eijui 1 ibr Him
ul pol In tau C in
aacit mtdi a

-*


Using aggregate load-
ing escinutes. and
rates fiom previous
steps , estimat u concen-
tratJon ranges in c.u.li
mei.1 ia , both fi>i
gdderal and i>pecifit:
(1 1st 1 1 !»ut Jijut. ol soiiiVL-s.
Conduct "sen si t i vi Ly
analybis" to determine
va r i ous pa rauie te rs
--


Summarise cr 1 ti cat
pathways , concen-
trations , distri-
butions ; compare
with monitoring
data , and idenl i ty
expos ui e pi»tential


                                            KICUKK *)-J
                                                        DIACRAM OK CRITICAL  I'ATIHJAY/DISTRIBUTION F.ST1MATFON
                                                        MLTII01) FOR ENVIRONHI.NTAL  PATHWAYS  Atil) FATE ANALYSIS

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                      free radical oxidation, photolysis, adsorption to
                      aerosols, dry deposition,  fallout,  rainout,
                      scavenging

       Water          hydrolysis, photolysis, chemical oxidation, pre-
                      cipitation,  adsorption/desorption with sediments,
                      volatilization,  biodegradation

       Soil           leaching,  hydrolysis, surface photolysis, chemical
                      oxidation, volatilization,  uptake,  adsorption,
                      complexation

       Biota          biodegradation, metabolism, bioaccumulation,  bio-
                      magnification,  etc.

      Some of these processes may have been considered earlier,  since  they
 are ones that result in intermedia  transfer.   By using very  simple  models
 generalized rate equations,  or measured  values  reported in  the  literature'
 the rates or degradation or  transfer within media  can be estimated
 Those processes are identified that  are  major  determinants of  the rate
 levels   "'  decomposition'  or ruction,  and hence  the ambient  concentration

      The next step is to utilize the aggregate loading rates,  general
 partitioning estimates, and the estimated transfer or reaction rates to
 calculate likely ranges of concentration of the pollutant in the environ-
 mental media.  Frequently, these calculations  will involve  "single
 compartment" models or equations along with physical/chemical  properties
 One would assume that the entire loading of the pollutant enters one  medium
 with a specific volume, and estimate the resultant concentrations of
 pollutant, changes over time,  and/or steady-state  concentrations
 Steaay-state values will be  important for highly persistent  pollutants;  trans-
 formation and transfer rates control the concentration distribution of
 pollutants tnat are more mobile or  shorter-lived in the environment
 w?ll°h^areSK  36Verai enjironmental compartments  (and/or decay processes)
 will nave to be considered simultaneously,  where both are important.
  Feedback  from one set of calculations  to  another  is required    In
 general,  however,  these estimates are made  to  place boundaries  on the
 distribution and concentration of the pollutant and not  to determine
 absolute  values.   Thus,  use  of more  complex, multi-compartment  or sinale
 compartment  models  may  not be  necessary  or  appropriate for this  approach.

     Estimates of environmental concentration ranges can then be mad*  cor
smaller geograpnical locations, using specific  source loadings  and
parameters describing the associated receiving  media.  A number of simple
models are available for this approach, for example, Mackay's fugacUv
model  (Mackay 1979) and simple computer models  such as PLUME
(EPA 1979), among others.  These models are described in grea^er
detail in Section 5.3.3.    Sensitivity analvsis can be conducted to
determine which parameters influence  the  outcome to  the greatest extent

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      The  final step  in  this approach  is  to summarize  the  results  in  terms
 of  the  critical pathways, estimates of  the environmental  distribution  and
 pollutant concentration ranges., and comparison of  these concentration
 ranges  with available monitoring data.

      This overall method  is appropriate  for considerations  in  several
 situations:

      (1)  when the pollutant  is not well-known and  few laboratory  or
          field environmental data are available;

      (2)  where there are only a few  types of important pollutant
          sources, and where distributions can be easily  estimated,
          or where data exist on major releases in  specific areas;

      (3)  where monitoring data are sparse, or are  widely distributed
          or uncorrelated with release patterns;

      (4)  where insufficient data and resources are available  to use
          more complex environmental models, or where the quality  of
          input data does not justify their use;

      (5)  in specific situations identified by using the environmental
          scenario method.

 5.3.3  Modeling Approaches

     As indicated earlier, simple calculations and modeling approaches
 are an  integral part of the environmental scenario and critical pathway/
 distribution estimation methods.   However, these stuple models usually'
 do not account for intermedia transfers and equilibrium relationships'
 between different media.  Multimedia modeling may be warranted, resources
 permitting, if sufficient data exist on the chemical,  physical and
 biological characteristics of the pollutant,  if accurate source and
 loading data are available,  and. if appropriate models  are available.
 The results of such models can provide a more accurate estimated dis-
 tribution of the pollutant in the environment and provide a useful
mechanism for estimating the effects of different regulatory approaches.
Once the models have been validated  and calibrated,  they  can be'used  in
many situations with modest  resource commitments.
are:
The general steps to be followed in multimedia modeling approaches


(1)  Identify, from materials balance results,  the major pollutant
     sources and geographical areas considered  for modeling.

(2)  Identify the most significant environmental pathway for  the
     pollutant under the conditions selected  above.
                                5-12

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        (3)  Select the individual models or multimedia model applicable
            to  the situation, i.e.,  type of emitting source, pollutant,
            receiving media.

        (4)  Compile the input data required by the model(s) selected,
            e.g., source/loading data, pollutant characteristics and
            properties, environmental characteristics, and time.

        (5)  Use the model(s) to estimate pollutant fate  (transport,
            transformation, concentration) in the different media.

        (6)  Compare the model results to the results of  the two approaches
            described above, and to monitoring data.  Comparison with
            monitoring data is frequently required for calibrating the
            model, and should be carefully accomplished before the model
            is used for predictions.

        (7)  Perform a sensitivity analysis of model parameters that are
            uncertain, or vary significantly in different locations.

        (8)  Analyze modeling results  for insight into exposure of various
            species,  effects of regulatory actions, impact of reduction
            in loading rates on environmental levels, significance of
            environmental process in  determining pollutant fate,  etc.

      A number of  computer  models have been  sponsored by  the U.S.
 Environmental Protection Agency  and  other agencies  to aid  in pollutant
 environmental fate and exposure  assessments.   Information  about  specific
 models is not reiterated in this report; instead,  the reader is  referred
 directly  to EPA's Environmental  Modeling Catalogue  (U.S. EPA 1979) for
 detailed  information  on available models.   Other model reviews include
 Miller (1978),  among  others.

      Some examples of available models considering a single environ-
mental  medium include the  EPA UNAMAP system (air), EXAMS (surface water)
EXPLORE (stream), ARM (watershed) and SESOIL (soil).  Examples of multi-'
media models that link two  or more environmental media includ<= UTM and
ALWAS  (air to watershed/stream), CMRA (overland to stream), and TOHM
 (air to watershed/water).   Other models include Mackay's fugacity method
which estimates equilibrium partitioning of a pollutant between air
water,  sediment and biota  (Mackay 1979), and Neely's microcosm model
(Neely 1978).

     Most pollutants released to the  environment are likely to be trans-
ferred between media.   A model can provide a fairly detailed  approach
for tracing pollutant  levels in different media when the substance is
subject to removal or  transformation  by  competing processes.   By  account-
ing for tne net rate  of  pollutant transport  or transformation,  the  model
                                  5-13

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 cnaracterizes che pollutant's mass distribution in the environment,
 temporal and spatial.   Sensitivity analysis enables determination of
 the significance of a particular process or variable.  With an
 efficiently developed model or set of models,  assuming input data are
 available,  the modeling approach can provide valuable information,
 in a timely and cost-effective manner.

      However,  currently there are significant  difficulties in applying
 multimedia  models to most  pollutants.   Although a considerable amount
 of research has been done  in this area,  most of the multimedia models
 are still under development or have  not been fully verified.   Adequate
 data (either chemical  or environment specific)  for input  to models
 are also often lacking.  When the input data used are uncertain or must
 be estimated,  the results  lack precision.   The  unavailability of a
 suitable, verified model and/or sufficient  input  data precludes the use
 of multimedia  models in  many instances.  When multimedia  modeling is
 performed,  results must  be  interpreted  with care,  because a selected
 model may exclude certain  pathways related  to the  complete traverse of
 the substance  through  the  environment.   Since the  results are obtained
 from environmental conditions,  a scientist  has  to  be  concerned with
 the extrapolation of the conditions  simulatued  to  generalized results
 and environments.

 5'4  EXAMPLES  OF ENVIRONMENTAL PATHWAYS AND FATE  ANALYSIS

      Several illustrative  examples of the methods described earlier are
 presented in this section.   Only portions of the  calculations, re=u^ts
 or discussions are given to indicate the types  and results of the approaches.

 5•4•1   Environmental Scenario  Method

     In an  exposure  and  risk assessment  for  copper  (Perwak at al.  1930)
 the environmental scenario  method was used  to link  sources  a^d~p~athwavs
 with environmental distribution.  This method was  selected  for this   '
 pollutant because sufficient monitoring  data were availabl* for  esf-
 mating  exposure,  and field  and  laboratorv studies had documented  the
 physical, chemical and biological processes  that determine  the pollu-
 tant s  behavior in the environment.  Figure 5-4 depicts the major  environ-
 mental  pathways for  copper  released  to the environment through human
 activities.                                                  5  '

     Figure 5-5 shows in greater detail environmental scenarios for
 several of the environmental pathways of copper.  In the second scenario,
wastes  from primary copper production,  coal  mining, and copper ore mining
and benefication are shown to enter the air  and water environment by
 several paths;  runoff and leaching mechanisms carry wastes to surface water
or^ ground water, respectively.  The surface  water/sediment interaction and
other flows  are also shown.  In the fifth scenario, several uses of copper are

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            /. Olhei Anthro-
             pogenic Source*
             of Copper
                          Copper Mining
                          and Piuiluclion
                          Other Oie Minuiy
                                                                        Runutl .mil W«lc Wdtei


                                                                                >i>l and Oiy fallout
                                                                Land
                                                              Surface Soils
                                                              I.iliiuji Piles
                                                              Laguoni
                                                              Landfillt
                                                              etc.
                                                                                                   J Occam
                                                                                          Suiliicc Waters »rxl Scdimcntl
                                                                                       Gruuridwater
Noie:   Quantities of coppei moving in each pathway are roughly piopottional to the thickness of each pathway shown.
       Slow movement from gioundwateis to surface waters not shown.

                           FICURE  5-4  EXAMPLE OF ENVIRONMENTAL SCENARIO  IDENTIFICATION-
                                        SCHEMATIC DIAGRAM OF MAJOR PATHWAYS  OF COPPER
                                        RELEASED  TO THE  ENVIRONMENT  BY HUMAN ACTIVITIES

                           L.  An  exposure  and risk assessment for  copper.   Final  Draft  Report.  Contract
                  .           Washington,  DC:  Monitoring and  Data Support Division, Office of  Water
          KeguLations and  Standards, U.S.  Environmental. Protection Agency 1980

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Ul
I
      PATHWAY NO.
           la.
           2.
Atmospheric binissions
 (Major Point Sources)
  CuO. CuS. Cu(m)
                    Cu Production
                    Smell my
                    lion & Steel Production
                    Coal Combustion
                    Incineration
                      Atmospheric Emissions
                        (Non point Sources)
                      CuO (paniculate). Others
                       —•**» O''1'
                        \w»b
                    Chrome & Brass Coicusion
                    Oil & Lubricant Combustion
                    & Leakage
 Solid Waste & Tailings,
  Coal Piles & Open
      Pit Minus
                     Prmiaiy Cu Production
                     Coal Minmy
                     Ore Mining and Beneficial ion
                                                                                            Pathway
                                                                      Pavement & Local
                                                                         I to.id Soils
                                                                       Surlace Waters
                                                                         Sediment
                                                         (Slow)
                                                                        Groundwater
Dissolved Solids
Stisp. Sediment
                   FIGURE  5-5   EXAMPLE OF  ENVIRONMENTAL SCENARIO ANALYSIS-TYPICAL  ENVIRONMENTAL  PATHWAYS OF COPPER
         Source:
                   WMm'^7a-'u Aln.exP°tlll«,1und  rlsk  aaaessment for  copper.   Final  Draft Report.   Contract
                   MA 68-01-3857.   Washington,  DC:  Monitoring  and  Data Support Division, Office  of Water
                   Regulations  and Standards, U.S.  Environmental Protection Agency;  1980.

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          > Discharges
    Senefic laiion
    Smelting
    Cu Production
    Elraii
    Electroplating
1 t
4 POTW ^ Primary
Intluent Tre.ilini.-iit *"
i , , 1. — 	 _ 	
1
(iintui)ical
4
"



ElflllLMII


Sullaci; Waters A
Si.'climciili, •
Ocean DiirnpiiH) Ty
Incin
ei .iiuiii
Land "~
I'll b


Air

So.l

(Slow)
<
Giuundwaier


^" (X:i;.nii


KH.RE  5-5  KXAMl™ OF ENVIRONMENTAL  SCliNARIO ANALYSIS-TY1TCAL ENV1RONMBNTAL PATHWAYS  OF COPPER  (Continued)

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 shown — as  an algicide (CuSO/^)  and as  an agricultural chemical.   The path-
 ways from  soil to  ground and surface  water,  to  sediments,  and ultimately
 to the ocean are shown.

      These general descriptions  were  the starting  point  for subsequent
 literature review,  quantification of  flow rates  fron selected sources,
 and ultimately analysis  of  concentrations in the environment.  For
 example, in order  co  describe  the first scenario,  the nature of solid
 wastes and tailings was  reviewed,  along with data  from studies  of acid
 mine drainage,  concentrations  found downstream  of  mine drainage sites,
 incidents  of groundwater contamination,  and  leaching studies from a
 variety of sites.

      The analysis  revealed  that  solid wastes, coal piles,  and tailings
 are major  sources  of  copper disposed  of on land.   Copper exposed as a
 result of  mining practices  is  subject to greater translocation  in the
 environment than releases from the other two  sources  due to the acid
 nature of  the leachate.   Surface  streams draining  mined areas have been
 shown to have localized  spikes in  copper concentration, with the level
 quickly decreasing  as  the stream  recovers  in  pH  and  alkalinity  values as
 a  function of distance.   The major processes  affecting this reduction in
 copper concentration  are dilution, sorption,  and precipitation.

      In municipal waste  landfills  the copper  concentration  in leachate is
 typically  between 0.04-0.4  mg/1.   Copper  is  quickly  attentuated by the
 soil.   Data on  groundwater  contamination were not  available though' such
 contamination is rare  in a  properly operated  landfill.  In  old  mined
 areas,  acid mine drainage,  and porous tailings enhance the  possibili
 of  grcundwater  contamination.

     For the  fifth  scenario involving the agricultural use of copper
sulfate, data describing the fa:e of copper in the soil, water and' sedi-
ments were analyzed; field data were examined for indications of the
roles of adsorption or sedimentation of copper and for mean and maximum
concentrations in water or sediment.  Use of copper sulfate as an algicide
appears to be effective within a very short time frame, and field studies
indicate that concentrations of copper ion in the water column decrease
to background levels within a day following application.  Copper is trans-
ferred from water to participates, algae and sediments through sorption.
Sediment core concentrations reflect the use of CuS04 over the years in-
dicating that sediment is a significant ultimate reservoir for copper in
aquatic systems.

5-4.2  Critical Pathway /Distribution Estimation Method

     The Critical Pathway /Distribution Estimation Method was used in the
pathways and fate analysis for pentachlorophenol (PCP) (Scow et_ al.  1980)
which is characterized by limited monitoring data, adequate d~ata~on basic
chemical properties, and a good general understanding of its overall
materials balance.   Little documentation was available on PCP  emissions
from particular consumers or producers.  The critical pathways approach
                                  5-13

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 was used in a risk assessment of this pollutant in order to provide PCP
 concentration estimates in various media and to determine the critical
 pathways influencing its distribution.  Since PCP use is concentrated in
 a few industry categories, the fate and pathways analysis was focused on
 these operations.

      In order to provide a better understanding of the fate, distribution
 and potential for exposure to PCP following discharge from significant
 sources, simple quantitative models were used.   Four sources to air were
 considered for their contribution to national atmospheric levels of PCP.
 Three sources—cooling towers, wood preserver evaporation ponds, and
 direct aquatic discharge as a general phenomenon—were considered for
 their local impact and exposure potential.   The type of input data required
 included source characteristics (e.g., dimensions, emission or loading
 rate,  etc.),  environmental characteristics  for  a representative set of
 conditions (e.g., wind speed and direction)  and chemical characteristics
 (e.g.,  transformation rates).   As an example of how the approach is
 applied,  the  development of the equation describing local'pollutant con-
 centrations from a cooling tower plume is described briefly.

      First, the assumptions made in developing  the equations  were defined.
 These  assumptions included the values  chosen for each  variable,  such as
 plume buoyancy and height,  wind speed,  temperature,  and others.   Also,
 variables  not included in  the  equation but  potentially influencing the
 resulting  concentrations were  identified (e.g.,  rainout,  large-scale
 turbulence, chemical  reactivity).   Second,  the  fate of pentachlorophenol
 during  cooling tower  evaporation was characterized by  a Gaussian concentra-
 tion distribution using  a  simple  plume  model.   The  output of  the model
 equation—PCP concentrations as  a  function of distance from the  source
 for two plume  source  heights—were  plotted,  as  in  Figure  5-6.  The  results
 of  the  equation were  used  directly  as  concentrations"from which  to  estimate
 human  exposure in subpopulations residing within specified  distances
 of  a  cooling  tower.

 5.4.3  Modeling Approaches

     Computerized and hand-calculator models have been used in the environ-
 mental ..fate and pathways analysis of numerous priority pollutants.   Three
 approaches  applied in  exposure and  risk assessments for phthalate esters
 (Perwak et al. 1981) and dichlorobenzenes (Harris et_ _al_. 1931) are described
 below.  (No example is given of the application of a complex multi-media
 model, though such models will undoubtedly prove to be useful in  future
 exposures and risk assessments.)

 5.4.3.1  Phthalate Esters

     Based on two existing environmental fate models for phthalate
esters:  The Exposure Analysis Modeling System (EXAMS), developed by
 the U.S. EPA  (Wolfe et_ _al_.  1979), and Neely's partitioning model  (Neely
 1978),  ambient concentrations of di(2-ethylhexyl) phthalate (DEHB) were
estimated in a simplified three compartment  model for water (including
sediment and fish).  Some of the model's assumptions were adapted in
 this application to incorporate more current or  relevant data develoned

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            10
              -3 _
                         Nonbuoyant Plume Source Height • 10m
          C
          8
          cj
         T)
          5
         5
         "3
          "
          o
10
 i
         I
            10'
            10*
                     Buoyant Plume Source Height = 120m.
              •4 _
                                                       10
                                  km Downwind
        FIGURE 5-6  EXAMPLE OF  USE  OF SIMPLE QUANTITATIVE MODEL TO
                    ESTIMATE ENVIRONMENTAL DISTRIBUTION—GROUND-LEVEL
                    CONCENTRATIONS  OF PENTACHLOROPHENOL IN THE PLUME
                    DOWNWIND OF A COOLING TOWER (TWO SOURCE HEIGHTS)
Source:  Scow, K". et al.  An exposure  and  risk assessment for pentachloro-
         phenol.  Final Draft Report.   EPA Contract 63-01-385?'.  Washington,
         DC:  Monitoring and Data  Support  Division, Office of Water Regula-
         tions and Standards, U.S.  Environmental Froteccion Agency: 1980
                                   5-20

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in the materials balance and in the review of physical and chemical
properties.  Some of the data were scaled for a national approach  from
a site-specific approach.

      Concentrations in air in the U.S. were estimated using the equation:


                           dx     Q   ,
                           27  =  I " kx
 where:   x  =  mass  concentration
         t  =  t ime
         Q  =  area  source  strength
         H  =  mixing height
         k  =  rate  constant for removal.


      The concentrations  predicted by the  models  for DEHP  in  water, sedi-
 ment,  fish and air  were  then compared with  measured concentrations reported
 in  the  literature.   Figure 5-7  summarizes the  predicted and  measured levels,
 The  results  of this analysis indicated that  DEHP  is usually  presenc  ac
 extremely low  concentrations in air,  and  at  low levels in water;  it  is
 subject  to significant chemical transformation in air but virtually  none
 in water;  and  it is likely to accumulate  in  sediment and  fish  to  levels
 from two to  three orders of magnitude greater  than water  column concentra-
 tions.

 5.4.3.2   Dichlorobenzenes

     For the environmental  distribution analysis  of 1,2-dichlorobenzene.
 two  separate fate models were implemented and the  results compared.
Mackay's  Level  I fugacity  approach was used assuming  all environmental
compartments—air,  water,  sediments,  biota—were  at  equilibrium and
connected  and  there was no  degradation or transport  out of the selected
environment.  The EXAMS model was run for three generalized, pre-compiled
aquatic  systems—a  pond, an oligotrophic lake and  a  river.   Input  data
to both models were based  on materials balance information and physical/
cnemical properties of dichlorobenzene compiled from published literature.

     For  typical environmental loading rates, both models predicted a
high sediment  to water ratio (two to  three orders of magnitude) under
equilibrium conditions, and partitioning into biota.  Table 5-1
summarizes the results.  Table 5-2 gives more detailed results of  the
EXAMS model.  Volatilization was the primary means of disposition from
ponds and lakes, aquatic systems in which transport downstream is
minimal.  The differences in the results of the' two models were due to
the fact that a greater proportion of dichlorobenzene partitioned  to
the air compartment  in the  Mackay  model and the fact that  EXAMS
considered kinetic  processes, as well as simple partitioning.

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                                            Mostly Degraded
                                            by Oil-reaction
                                                  t


Calc.
Obs.
.concentrat
AIR
Remote
0-.008
.0004
ions in ]i

Urban
.02-. 09
.3
8/m3)
                                           4.3 x  103  kkg/yr

                                           5.3 x  JO3  kkg/yr
Ul
1
t-J

SEDIMENT
Calc. 5-50
Obs. 20-200
( i ' 1 1 n r P n r r ;\ t i .•» n Q in m o / U u \



—ml - -

1
WATFR
Calc. .006-. 06
Obs. .001-. 05
( coiicen tra t ions in nig/1)
1

r>»

FISH
Calc. 4-38(30-day exposure)
Obs. 0.3-3
(conceiitiatioiia in mg/kg)

                                            Mostly  Exported
l-'fCIJRK 5-7  EXAMPLE QV RESULTS OP MODELm\ OF ENVIRONMENTAL DISTRIBUTION—COMPARISON OF CALC'W ATFD
            AND OBSERVED LEVELS OF DI (2-ETHYi,llEXYL) I'HTHALATE IN AIR, SEDIMENT, WATER AND  FISH

Source:  Perwak, .1. et al.  An exposure and risk assessment fur phthalate esters.  Final. Draft Report
         Hl'A Contracts 68-01-3857, 5949.   Washington, DC:  Monitoring and Data Support Division
         Oil ice of Water Regulations and  Standards, U.S. EnvironmentaJ Protection Agency;  1981.'

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      TABLE 5-1.  EXAMPLE OF RESULTS OF MODELING OF ENVIRONMENTAL
                  DISTRIBUTION—COMPARISON OF RESULTS FROM MACKAY' S
                  EQUILIBRIUM MODEL AND EXAMS FOR 1,2-DICHLOROBENZENE
                  IN A POND SYSTEM
  EXAMS Results
  (Pond,  24 kg/day loading
  370 kg  steady state accumulation)
              Maximum Concentrations
  Water
  Water Biota
  Sediment  Biota
  Sediment
  3.0 mg/1
630 mg/kg
610 mg/kg
460 rug/kg
                     Mackay   Results
                      (370 kg  in system)
Water
Water Biota
Sediment Biota
Sediment
Concentrations
  0.0559 mg/1
 18 mg/kg
 12 mg/kg
 35 mg/kg dry
    weight
             Accumulation
  %  in Water
  %  in Sediment
16.22
83.78
Percent of Chemical per Compartment
Z in Water3       0.30
% in Sediment    64.4
  :Part  of  the  initial  aquatic  load  has  been  removed  by  volatilization.
Source:   Harris,  J.  et al.   An exposure and risk  assessment  for  dichloro-
         benzenes.   Final Draft Report.  Contracts EPA 68-01-5949, 6017.
         Washington, DC:  Monitoring and Data Support Division, Office of
         water Regulations and  Standards, U.S. Environmental Protection
         Agency;  1981.
                                   5-23

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    TABLE 5-2.   EXAMPLE OF RESULTS  OF MODELING OF ENVIRONMENTAL DISTRIBUTION-
                    EXAMS  OUTPUT  FOR 1,2-DICHLOROBENZENES
            a.  Steady-State Concentrations of 1.2-dichlorobenzene in various  generalized aquatic
                systems  resulting from continuous  discharge at a rate of  1.0 kg/hour3

                                    Maximum Concentrations
Oligotrophic
Lake

River
Loading
(kg/hr).
1.0
1.0
1.0
Water
Dissolved
(mg/1)
3.0
0.15
0.00099
Water
Total
3.0
0.15
O.C009
Maximum in
Sediment
Deposits
(rag/kg)
460
0.73
9 0.024
'Plankton
(ug/g)
630
30
0.21
Total
Steady-State
Benthos Accumulation
(Ug/g) (kg)
610 370
3.3 410
o.nis i i
                                                                 Total
                                                                 Daily
                                                                  Load
                                                                  (kg/dav

                                                                   24


                                                                   24


                                                                   24
            b.  The fate of 1,2-dichlorobenzone in various generalized  aquatic systems'

                Percent  Distribution	Percent Lost by Various  Processes
Oligotrophic
Lake

River
                                                         Transformed
              Residing in    Residing  in    Transformed   by                        Lost        Time for
              Water at       Sediment at    by Chemical   Biological                by Other    System Se!
              Steady-State   Steady-State   Processes _   Processes    Volatilized   Processes^  Purificnri
               16.22
               75.52
83.73


 1.39

24.48
0.0


0.0


0.0
0.05

0.0

0.0
91.91


94.64


 1.44
 3.05

 5.36

98.36
                                                                                                282.3
                                                                                                 13.19 d;
      data  simulated by the EXAMS (U.S. EPA-!,ERL, Athens, Ga.)  model  (see  text  for further Information).
  Including loss through physical transport heyond system boundaries.

  Estimate  for  removal of ca.  97= of  the toxicant accumulated  in system.   Estimated from the results of
  the half-Lives for the toxicant in  bottom sediment and water  columns, with overall cleansing ttmo
  weighted  according :o the pollutant's initial distribution.

  Source:   Harris,  J.  e_t  a_l.  An  exposure inc.  risk assessment for dichlorobonzenes.  Final Draft Report.
           Contracts EPA  68-01-5949, 6017.   Washington,  DC:  Monitoring ,ind Data Support Division. O
           of Water Regulations and Standards., U.S.  Environmental Protection Agency; 1981.

-------
                               REFERENCES
 Harris, J.; Coons, S.; Byrne, M.; Fiksel, J.; Goyer, M.; Wagner, J.;
 Wood, M.; Moss, K.  An exposure  and risk assessment for dichlorobenzenes
 Final Draft Report.  Contracts EPA 68-01-5949 and EPA 68-01-6017
 Washington, DC:  Monitoring and Data Support Division, Office of'water
 Regulations and Standards, U.S. Environmental Protection Agency; 1981.

 Lyman, W.J.; Reehl, W.F.; Rosenblatt, D.H.  (eds.)  Handbook of chemical
 property estimation methods.  Environmental behavior of organic compounds.
 Boston, MA:  McGraw Hill; 1982.

       1979  Flndin§ fuSacit? feasible.   Environ.  Sci.  Technol. 13:1218-
 Miller,  C.   Exposure assessment modeling,  A.  state of the art  review
 Contract _ EPA PB 600/3-78-065.   Athens,  GA:  Athens Research  Laboratorv
 U.S.  Environmental Protection  Agency;  1978.

 Neely, W.B.   A preliminary  assessment  of the  environmental exposure  to
 be expected  from the addition  of  a  chemical to  a  simulated aquatic
 ecosystem.   Intern.  J.  Environ.  Studies 13:101-108;  1979.
         J  ;  Bysshe,  3.; Goyer, M. ; Nelken, L. ; Scow, K. ; Walker, P.-
 Wallace, D.  An  exposure and risk assessment  for copper.  Final Draft
 Report.  Contract EPA  68-01-3857.  Washington, DC:  Monitoring and Data
 Support  Division, Office of Water Regulations and Standards, U.S
 Environmental Protection Agency; 1980.

 Perwak,  J.;  Goyer, M. ; Schimke, G. ; Eschenroeder ,  A.; Fiksel, J. ;
 bcow, K.; Wallace, D.  An exposure and risk assessment for phthala^
 esters.  Final Drart Report.  Contracts EPA 68-01-3857, 5949.  Washington
                         Support Division, Office of Water
and Standards, U.S. Environmental Protection Agency; 1981.

Scow, K.^ Goyer, M.;  Perwak, J.; Payne, E.;  Thomas, R.;  Wallace  D •
 ?   i '  *;! W?°d' M'   An exP°sure and ris'
-------
U.S.Environmental Protection Agency (U.S. EPA).   Environmental modeling
catalogue.  Contract EPA 68-01-4723.  Washington, DC:  Management
Intormation and Data Systems Division,  U.S.  Environmental Protection
Agency; 1979.

Wolfe, N.L.; Steen, W.C.;  Burns,  L.A.   Use of linear free energv rela-
tionships and an evaluation model for  phthalate transport and fate esti-
                                                     U'S' Environmental
                                5-25

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            6.0  MONITORING DATA AND ENVIRONMENTAL DISTRIBUTION
6.1  INTRODUCTION

     Monitoring data, as used in the context of exposure analysis, can be
defined as data on the concentration of toxic pollutants in the environ-
ment.  Ideally monitoring data indicate ambient concentrations over wide
geographic areas and different periods of time.  They are sometimes supple-
mented by data measured in field studies, which can be used to indicate
local conditions or special situations.

     Many different kinds of monitoring data may be useful in exposure
analysis.  Both well-mixed equilibrium concentrations and unusually high,
temporary spill or discharge concentrations are of interest.  The first
represents the long-term condition to which humans and other organisms
are typically exposed.  The second, although a short-lived condition,
could potentially have acute adverse effects on exposed organisms.  In
addition, for certain readily transformed or transferred chemicals, only
the second type of data will exist.  Depending upon the environmental
loading and fate characteristics of the pollutant, emphasis may be placed
on finding monitoring data pertaining to either long-term or transient
conditions.

     Traditionally,  monitoring data have been considered as measured
concentrations reflecting ambienc concentrations in surface water,
sediment, foodstuffs,  etc.   However,  for purposes  of estimating ex-
posure to pollutants,  information regarding concentrations  in  more
varied media are of  interest.

     Water—surface  water (fresh and  salt),  ground water,  raw  and  finished
     drinking water,  precipitation, POTW influent  and effluent,  landfill
     leachate, industrial effluent, urban  and rural runoff,  etc.

     Air—vapors,  aerosols,  and  particulates in ambient  air, industrial
     emissions,  automobile  emissions, workplace air environment, etc.

     Soils and sediments—dust;  surface and  subsurface soils;  bedrock:
     estuary,  lake,  river and  stream  sediments;  etc.

     Biota—soil and aquatic microorganisms,  vertebrates, invertebrates,
     mammals,  birds, organisms in a foodchain;  humans, including whole
     body or  organ tissues  such  as  human milk,  human  adipose tissue, urine
     and  blood serum.

     Food—milk, meat, dairy products,  grain, vegetables, fish, animal
     feed,  etc.  (both  in  a natural  and/or  prepared  state).
                                   o-l

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     Other--treated  items such as preserved wood, painted  objects,  food
     packaging, clothing, or any other product or item  that may  contain
     the compound of interest.

     Again, the particular media of interest depend upon the environ-
mental loading and pollutant fate characteristics.  For example, a  highly
volatile product may never be found at significant concentrations in soil
and water but at high levels in air.  A persistent compound with low
water solubility may be detectable only in sediments and soil.   Use and
disposal characteristics of the pollutant will also determine which media
to consider; for instance, some chemicals may be found only in the  air
of certain working environments.   Therefore, flexibility is required in
the methodology for analyzing monitoring data in order to allow  emphasis
on the important environmental reservoirs and sinks for various  pollutants
with a wide range of fate characteristics.

6.2  GOALS AND OBJECTIVES

     The primary goal of the monitoring data review within an exposure
analysis is to develop,  analyze,  and present comprehensive data on the
geographic distribution  of pollutant concentrations  in various environ-
mental media,  indicating trends or  changes  over time if possible.  Spe-
cific objectives include:

     (1)   In the initial definition and focusing of  risk assessments,  an
          analysis  of monitoring  data  is  used to  characterize  the behavior
          of a pollutant in  the environment;  to determine  whether local,
          regional,  or national risks  are important;  to identify the geo-
          graphical areas  of concern;  and when  combined with effects data,
          to reveal the  significance of the potential  risks.

     (2)   In some circumstances,  when  monitoring  data  are  sufficiently
          extensive to be  representative  of typical  environmental concen-
          trations,  they provide  a  description  of environmental  distribution.

     (3)   In the analysis  of monitoring data, baseline  levels  can sometimes
          be established (ambient conditions) for comparison with concen-
          trations  in polluted  environments.  In  such  an analysis,  for
          example,  background  concentrations  near ore  deposits may be  found
          to be  equal to or  greater  than  those  found in  some industrial  areas.

     (4)   Monitoring  data  can  be  used  to  confirm  materials  balance and  en-
          vironmental fate analyses, to provide a credible  basis  for extra-
          polating  materials  balance and  fate considerations, and to provide
          input  data  for large-scale modeling of  environmental fate.

     (5)   Monitoring  data  can  suagest  important routes  of exposure for
          humans as well as  other species,  provide direct inputs  to  esti-
          mates  of  exposure  (e.g., concentration  in foods for estimating
          human  exposure via  ingesticn),  and  to help define the risk to
          regional  and otrier  suboooulations.

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Though not all of these objectives will be met in each particular analysis,
they provide a framework to be used to the degree possible, depending on
the available data.

6.3  METHODS AND APPROACHES

     The approach to monitoring data analysis consists of three basic
steps:

      (1)  identification and systematic collection of data;

      (2)  evaluation, analysis and presentation of data; and

      (3)  interpretation and use of data in exposure analyses.

     At the start of a monitoring data analysis, materials balance studies
should first be reviewed briefly to help identify likely media for emphasis
in the systematic search for monitoring data.  It will also be important
to define the boundaries of the search for monitoring data—the geographic
focus, depth and breadth—so that the necessary effort is devoted to this
portion of the risk analysis.  Also, a desired format for the presentation
of data should be developed early in the work.  The initial focusing step
in a  risk analysis will aid this process.

      Collection of data should be based upon a systematic literature
search.  The U.S. Environmental Protection Agency, through its air and
water quality programs, provides a comprehensive source of monitoring data.
Particularly important for risk analyses will be the STORET system, NASQAN
(National Stream Quality Accounting Network), SAROAD (Storage and Retrieval
of Aerometric Data), NOMS (the National Organics Monitoring Survey), the
Pesticide Monitoring Program, the Air Quality Monitoring Program, the
Human Tissue Monitoring Program, etc. (see Chapter 10 for a listing).
The STORET system, maintained by the Office of Water Regulations and
Standards of the U.S. Environmental Protection Agency is a centralized
system for storage and retrieval of water quality data.  The largest file
in STORET is the Water Quality File which contains data concerning 40
million observations at more than 200,000 monitoring stations in the U.S.
These data are of graat use in considering the distribution of a chemical
in the environment.  Another STORET file that often contains pertinent in-
formation is the Fish Kill File, which provides detailed and summary data
on major pollution-caused fish kills dating from 1960.  Thus, in addition
to the traditional methods of literature search, the U.S. Environmental
Protection Agency centers responsible for these monitoring systems should
be contacted in order to obtain the most up-to-date data, provided the
scope of the exposure assessment warrants.

      In addition to the U.S. EPA, computerized data bases and publications
of other federal agencies should be consulted such as the U.S. Geological
Survey, Department of Interior, Department of Energy, Department of Health,
Education and Welfare, Consumer Product Safety Commission, the National
                                  6-3

-------
Aeronautics and Space Administration, National Occartographic and Atmos-
pheric Administration, and the Corps of Engineers.  Many of these agencies
and sources have compilations o£ literature data which may be useful.

      In evaluating monitoring data for use in exposure assessments, a
series of questions should be posed:

      (1)  How, where, and when were the monitoring data obtained?

      (2)  Was the sampling process adequate to represent the environmental
          compartment or subcompartment being monitored?

      (3)  Were the analytical methods used appropriate to the monitoring
          problem and to the pollutant being measured?

      (4)  What were the sensitivity, reproducibility, and confidence of
          the analytical results?

      (5)  How were the data aggregated and reported?
          i
     The answers to these questions are not always available,  and differ
for every study and every pollutant.  Frequently, monitoring data are not
complete because results are reported for samples taken from only a few
geographical locations.  As a result, it is often difficult to determine
whether the monitoring data are applicable only to specific geographical
locations or whether they are representative of general levels in the U.S.
The numerical concentration values presented in monitoring data must be
used with caution because detection limits, accuracy,  and precision of
the measurements are frequently not reported.   The analytical  methods used,
potential interferences, and details of the measurement approach (for
example, whether the measurement: represents the total metal concentration,
specific ionic species, or whether a specific  chemical or family of
chemicals, e.g.,  phenols,  are included).   Frequently little informa-
tion is given on the seasonality or other temporal variations  in the
measurements.   Another problem associated with monitoring data is that
other parameters useful in interpreting the data, such as suspended solids,
pH, or the presence of other chemical species,  may not be given.  Perhaps
the most frustrating aspect  of monitoring data is the lack of additional
information that helps the investigator determine whether or  not the
monitoring data are sufficiently representative to be  used in  an exposure
assessment.   When reporting monitoring data,  it is essential  to provide
complete references and give any additional information that was reported
in the original reference.   Because of these limitations,  monitoring data
do not always  provide a clear ar.d accurate verification of real environ-
mental concentrations of pollutants and may,  in some cases, yield no better
information than estimates  obtained from fate  and pathways analysis.

     However,  monitoring data represent the only  evidence of actual ex-
posure, since  many aspects  of materials balance development and fate
analysis are highly speculative.   Therefore, although  there may be  some

-------
uncertainty about values used, monitoring data should be used whenever
possible in an exposure assessment.

     The presentation of the available data is a difficult problem in
some cases, and to an extent depends upon how the data will be used. The
data may be summarized for presentation as maps, charts, graphs, tables,
overlays, etc.  Attention to presentation style is important, since this
often effects the conclusions that are drawn from the data.  Uncertainty
in the data should be indicated in the presentation.  Ranges, average
and median values, and concentration frequency distributions should be
presented, along with detection limits, wherever possible.  Illustration
of data trends (such as decreasing water concentrations over 10 years)
provides useful information on the anticipated impact of increased pro-
duction or tighter environmental regulation on pollutant concentrations.


6.4  EXAMPLES OF MONITORING DATA

6.4.1  Copper and Silver

     A tremendous amount of monitoring data has been collected for copper
in all media  (Perwak et al. 1980).   Copper levels in aquatic ecosystems
(water, sediment, fish) are available from the EPA STORET data base.
Figure 6-1 shows the distribution of total copper observations for the
U.S. from 1970 to 1979.  Obviously, this type of a figure cannot be used
directly in an exposure analysis, but it does give some indication of the
range of total copper concentrations that are found in the U.S.

     The monitoring data can also be aggregated by major river basins,
which represent large areas of the country.   They can be depicted geo-
graphically as is shoxro in Figure 6-2 for silver (Scow e_t al.  1981) , or
displayed in tabular form.   The copper data for 1970-1979 aggregated for
major river basins are shown in Table 6-1 for water and Table 6-2 for
sediment.   By use of this technique,  certain areas of the country with
high copper levels can be identified.  However,  aggregation of data ever
such large areas can provide misleading results.   Therefore,  monitoring data
from minor river basins were  also examined,  including data  only for  1978.
Table 6-3 shows that numerous minor river basins  have mean concentrations
greater than 50 'i-g/1 total copper and at least 10% of the observations
greater than 120 ug/1.   However,  only a few locations had median levels
of total copper greater than 60 ug/1.  In addition,  some of these minor
river basins were identified  as having soft  water (<50 mg/1 CaCo^ ,  a
condition that increases toxicity.   These results suggested that within
these minor river basins showing  high mean levels,  most observations were
less than 60 ug/1 and a few were  greater than 120 ug/1.

     Data from individual monitoring  stations  in  four areas with high
average copper concentrations were  examined  and  compared with  information
on specific sources of  copper and evidence of  actual  impact on aquatic
biota.   This analysis showed  that high average copper concentrations
                                  6-5

-------
                              41
     30%
     20%
 55
c
 re
C/3
c
3
<£
10%
          <\
                 -
               P77!
                            i
                               44
                              i

                               y.
                                     10
                                          1.0
  -001    -01     -1      1     10    100

                    Concentration
                                           1,000   10,000   100,000
      FIGURE 6-1  EXAMPLE OF SURFACE WATER MONITORING DATA
                  DISTRIBUTION 3Y CONCENTRATION  RANGES—COPPER
                               1970-1979
      Source:   Perwak,  J. et al. An exposure and risk assessment
               for copper.   Final Draft Report.   Contract EPA 68-
               01-3857.^ Washington. DC:  Office of Water Regulations
               and Standards, U.S. Environmental Procecticn A.E
               1980.
                                  6-6

-------
                                       Hi r-"^,: :• E™ i.i.;;;
                                       •*$ L-^\J__ i iV/4';
                                       v4 I ' i     l~ *-»- Vi P'



Source:
 FJCUHE 6-2  EXAMPLE OF (.'EOGRAPHIC DISTRIBUTION OF MONITORINfi DATA FOR  SILVER


'iA^'7' r " exl^ostire  anj risk asseusment  for silver.
  J/, JJiJ, and  hi'A   68-01-6017.  Wash in

-------
          TABLE 6-1.   EXAMPLE OF SURFACE WATER MONITORING DATA
                      DISTRIBUTION BY MAJOR RIVER BASINS—COPPER
      Region

 New England
 Mid Atlantic
 Southeast
 Great Lakes
 Ohio
 Tennessee
 Upper Mississippi
 Souris  and  Red  of North
 Missouri
 Arkansas  and Red
 Western Gulf
 Hawaii
 Rio  Grande  and Pecos
 Upper Colorado
 Lower Colorado
 Great Basin
 Pacific Northwest
 California
Alaska
 United States
.100-1
ug/1
3
1
2
1
1
<1
<1
<1
<1
1
3
1
9

-------
         TABLE 6-2.  EXAMPLE  OF SEDIMENT MONITORING DATA DISTRI-
                     BUTION BY MAJOR RIVER BASINS—COPPER
                                    Percentage of Observations
 New England
 Mid Atlantic
 Southeast
 Great Lakes
 Ohio
 Tennessee
 Upper Mississippi
 Lower Mississippi
 Souris and Red of North
 Missouri
 Arkansas and Red
 Western Gulf
 Hawaii
 Rio  Grande and Pecos
 Upper  Colorado
 Lower  Colorado
 Great  Basin
 Pacific  Northwest
 California
 Alaska
United States               30       60
1-10
mg/k g
33
31
41
14
24
20
23
24
24
54
57
37
<1
16
53
40
14
18
10-100
rag /kg
50
53
56
65
73
69
58
72
41
39
43
59
33
84
46
40
81
75
100-1,000 1,000-10,000
15 1
15 
-------
                TABLE 6-3.  EXAMPLE OF SURFACE WATER MONITORING DATA
                            FOR COPPER 3Y MINOR RIVER  BASINS
River Basin Mean Cu >50X of Cu >102 of Cu
Major /Minor Name >
2/3
2/5
2/6
2/7
2/3
3/7
3/8
3/9
3/13
3/311
3/32
3/43
4/3
4/7
4/8
5/9
5/lfl
5/21
6/4

7/2
7/13
9/12
10/11
10/16
10/19
10/20
10/21
11/4
12/1
12/2
13/2
13/3
14/41
14/51
14/9
15/7
Delaware R. - Zone 1
Delaware R. - Schuylkill
Delaware R. - Zone 2
Delaware R. - Zone 3
Delaware R. - Zone 4
Yadkin & Pee Dee Rivers
Catawba - Wateref, etc. Res.
Edisto - Comb aha f R.
Savannah R.
Apalachicola R.
Choctawhatchee R.
Pearl R.
French Broad R.
Duck R.
Tennessee R.
Big Sandy R.
East Fork, White R.
Ohio R.
I. Erie Shore, Maumee R. to
Sandusky R.
Hudson Bay, Rainy River
Chicago Calumet R. - Des Plaines R.
Lower Missouri R. from Niobrara R.
Lower Mississippi R. - Yazoo R.
Lower Red R_ — below Denison
Atchafalaya R.
Calcasieu R.
Lower Mississippi R.
Gila R.
Sabine R.
Heches R.
Clark Fork - Pend Oreille R.
Spokane R.
Central CA Coastal
Santa Clara R.
Sacramento R.
Great Salt Lake
>502 of Hardr.
50 ug/L >60 ug/L >120 ug/L Measurements <
*
*

*
* *

* *
* *
* *
*
*
*
*
* *
*
*
*
* *

*
*
*
*
*
* *
* * *
*
*
* *
* *
* * *
* *
*
*
* *
* *
*





*
*
*
*

*
it
*






*



*


*


*
*

*


*

Fewer than 10 measurements at this  station.
     Source:  Perwak, J. at al. An exposure and risk assessment  for  copper.
              Final Draft Report.  Contract EPA 63-01-3857.  Washington,  DC:
              Office of Water Regulations and Standards. U.S. Environmental
              Protection Agency; 1980
                                        6-10

-------
 reported for some river basins were the result of a small number of very
 high concentrations.   The analysis of the Sacramento River showed that
 the mean from 26 to 27 stations for 1978 was less than 30 ug/1.  However,
 data for one station showed a mean level of 4585 ug/1 for that year.
 Furthermore, dilution volume and the nature of the receiving water
 (particularly pH and  hardness) had to be considered in conjunction with
 monitoring data in analyzing the risks of copper exposure for aquatic
 biota since sensitive species are known to exist in locations with high
 levels of copper.

 6.4.2  Pentachlorophenol

      Monitoring data  for pentachlorophenol (PC?) are sparse and exist for
 scattered media and sampling sites (Scow jat_al.  1980).   In 1980,  the
 total number of observations of PCP surfa~ce "water concentrations  in
 STORE! was 80.   Additional surface water data were limited to scattered
 observations of low levels in a small number of  geographic areas.   The
 compound was reported to be present in influents to POTWs, but also
 appeared to be  removed effectively by treatment.  PC? had been detected
 (again at low levels)  in a drinking water survey.   No data were available
 concerning levels  in  air or soil.

      Despite the fact that PCP did not appear to be found at high  levels
 in  aquatic media,  the compound was reportedly present in  some food products
 (Table 6-4)  and also  found commonly in human tissue and urine (Table 6-5) ,
 even in persons not occupationally exposed.   Thus  non-aquatic exposure
 routes had to be considered.   The  use of PCP  as  a  pesticide results  in
 numerous opportunities for human exposure,  particularly via inhalation.
 Since no data were available on ambient atmospheric levels,  fate models
 had  to be used  in  the  risk analysis to predict concentrations for  the
 most likely  conditions under which the general population might be  ex-
 posed (e.g.,  in the vicinity of preservative-treated  wood or open burning
 of  such wood  and downwind  of cooling  towers or wood  treatment wastewater
 evaporation  ponds).

 6.4.3   Dichloroethanes

      As  is the  case for many  organic  compounds, monitoring data for  the
 dichloroethanes are extremely  limited  (Perwak _et_ _al. 1982).   Very few data
 exist  showing levels in surface waters.  In fact, only 10 observations above
 the  detection limit were found  for  1,2-dichloroethane in  the STORET data
base  in  1980.  However, several reports of ground water contamination were
 found, as is shown in Table 6-6.  In addition, air concentrations have be°n
 reported in heavily trafficked areas, as well as  in highy industrialized
areas  (Table 6-7) .

     These limited results suggest  that exposure  occurs in specific areas,
but  that exposure to the general population is generally low.  Obviously
 the limited sampling of ground water and air does not provide a representa-
tive sample of widespread conditions.  In this case, generalizations about
exposure in other areas have to be made with caution due to the limited
sampling and the nature of the exposure route.


                                 6-11

-------
           TABLE 6-4.  EXAMPLES OF MONITORING DATA FOR FOOD
                       AND FEED—PENTACHLOROPHENOL
                  Concentration (yg/1 or ug/kg)
Sample

Dairy

Grain and Cereal

Leaf Vegetables

Root Vegetables

Garden fruits

Fruits

Sugars

Peanut butter

Bovine milk
Mean

 0.5

 1

 T

 1

 T

 T

 6

18

ND
 Range
Reference5'
 10       Johnson and Manske (1977)'

 10 -13   Johnson and Manske (1977)

 13       Johnson and Manske (1977)

 10       Johnson and Manske (1977)

 10       Johnson and Manske (1977)

 11       Johnson and Manske (1977)

 10 - 40  Johnson and Manske (1977)

1.8 - 62  Heikes (1979)2

          Lamparski et al. (1978)
ND - Not Detected

 T = average below detection linit.  Samples collected through U.S. in
     FDA's Market Basket Study.
2
 Market Basket Study - U.S.  population.

 Michigan dairy herds, detection level = 10 ug/1.

*
 See source indicated below for references.
Source:  Scow, K. et al. An exposure and risk assessment for pentachloroohenol
         Final Draft Report.  Contract EPA 68-01-3857.   Washington, DC:
         Office of Water Regulations and Standards, U.S. Environmental
         Protection Agencv; 1980.

-------
           TABLE 6-5.  EXAMPLE OF MONITORING DATA FOR HUMAN
                       TISSUE AND URINE—PENTACHLOROPHENOL
 Population and Sample                     	

 Exposed workers - urine (Japan)

 Non-exposed workers - urine (Japan)

 General population - urine (Florida)         4.9

 Occupational workers - urine (Florida)     119.9

 General Population - adipose tissue         26.3

 Occupational population - urine (Hawaii)  1302

 Non-occupational population - urine (Hawaii)  40

 Occupational/non-occupational population   217
                               - urine

 Combination of the above three  groups      537
                            (Hawaii)

 Occupational worker exposure  -  urine -
    by  wood preserving  methods  (Oregon)

         Dip                               2330
         Spray                             980
         Pressure                           1240

 U.S. General  Population  -  urine              6.3
 Concentration
(yg/kg  or-ug/1)
Mean
  Range

1100-5910

  10-50

 2.2-11.2

22.2-270

  12-52

   3-35700

  ND-1840

   3-38642
          120-9680
          130-2580
          170-5570

          ND-193
Reference"

Bevenue (1967a)

Bevenue (1967a)

Cranraer (1970)

Cranmer (1970)

Shafik (1973)1

Bevenue (1967b)~

Bevenue (1967b)

Bevenue (1967b)
           ND-38642     Bevenue  (1967b)
                       Arsenault  (1976)
             Kutz  (1978)'
ND - Not Detected

1 Detection limit - 5 ug/kg.

Detection limit = 3 ug/1.

Detection limit - 5 ug/1.

*Detection limit « 5-30 yg/1.
"See source identified below for reference.
Source:  Scow, K. ejt al.  An exposure and risk assessment for penta-
         chlorophenol.  Final Dcaft Report.   Contract EPA bS-Ol-jSS/,
         Washington, DC:  Office of Water Regulations and Standards,
         U.S. Environmental Protection Agency; 1980.

                                   6-13

-------
                  TABLE  6-6.   EXAMPLE OP CROUND WATER MONITORING  DATA FOR DIC1ILOROETHANES
                                                                 %  Positive
    Compound _     No.  Statea Tea ted    No. Wei Is Tea led       Samples        Maximum
 1,1-dlcliloroethane             9                   785                 18          11,'J30


 1,2-dlchloroethane             12                  1212                  7             400
Source:
Perwalc, .).  et a I.  An exposure and risk assessment for dichloroethanes.  Final Draft Report
Contract EPA 68-01-5949.  Washington,  DC:  Office of Water Regulations and Standards,
U.S. Environmental Protect Jon Agency;  1982.

-------
I
!-•
Ol
                            TABUS 6-7.   EXAMPLE OF MONITORING DATA FOR DlCHLOROETHANliS IN AMBIENT AIR
      City          No.

Niagara Falls, NY

Hahwjjy/Woodbridge,
Houndbrook, and
I'ussnic, NJ

fiat on Rouge, I.A

Houston, TX
        aNot  detected.
         Trace.
                                          o.
                                 ,   ,  Concentiatit>»
                              ampled  Ha,!aejtnfi/«3)
                                                                         1,2-Dichloroethane
                                       0/9
                                          NI)a
                                                                                 2/8
Concentration
Range (ng/m3|

  n\>
10/66
12/43
1/30
T-342
T-500
555
75/93
36/43
22/30
T-139,121
9-10,341
T-66,300
       Source:
Perwak, J. et al.  An exposure and risk assessment  for dichloroethanes.   Final Draft Report
Contact EPA 68-OL-5949.  Washington, DC:  Office of Water Regulations and Standards,
U.S. Environmental Protection Agency; 1982.

-------
                              REFERENCES
Perwak, J.; Bysshe, S.; Goyer,  M, ;  Nelken,  L.;  Scow,  K.;  Walker,  ?.;
Wallace, D.  An exposure and risk assessment for copper.   Final Draft
Report.  Contract EPA 68-01-3857.   Washington,  DC:  Monitoring and Data
Support Division, Office of Water Regulations  and Standards,  U.S.
Environmental Protection Agency;  1980.

Perwak, J.; Byrne, M.;  Goyer, M.;  Lyman,  W.; Nelken,  L.;  Scow, K.;
Wood, M.; Moss, K.  An exposure and risk  assessment for  dichloroethanes.
Final Draft Report.  Contracts EPA 68-01-5949  and EPA 68-01-6017.
Washington, DC:  Monitoring and Data Support Division, Office of Water
Regulations and Standards,  U.S. Environmental  Protection Agency;  1982.

Scow, K.; Goyer, M.;  Perwak, J.;  Payne, E.;  Thomas, R.;  Wallace,  D.;
Walker, P.; Wood, M.   An exposure and risk  assessment for pentachloro-
phenol.  Final1Draft Report.  Contract  EPA  68-01-3857.   Washington, DC:
Monitoring and Data Support Division, Office of Water Regulations  and
Standards, U.S. Environmental Protection  Agency; 1980.

Scow, K.; Goyer, M.;  Nelken, L.;  Payne, E.;  Saterson; K.; Walker,  P.;
Wood, M,; Cruse, P.;  Moss,  K.  An exposure  and  risk assessmenc for silver.
Final Draft Report.  Contracts  EPA 68-01-3857,  5949 and  EPA 68-01-6017.
Washington, DC:  Monitoring and Data Support Division, Office of Water
Regulations and Standards,  U.S. Environmental Protection Agency;  1981.
                                  6-16

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                       .0  HUMAN EXPOSURE AND EFFECTS
7.1  INTRODUCTION

     The consideration of human exposure to toxic pollutants and the re-
sultant effects is critical to 3. risk analysis or assessment.  In the
past, risk assessments have commonly considered only human health effects,
often focusing on studies with laboratory animals and the extrapolation
of animal data to humans.   As indicated earlier,  the integrated
risk analysis approach described in this report considers human exposure
and effects a vital element, but not the sole element, of a comprehensive
risk analysis.  In some respects, the human exposure and effects section
represents the culmination of the use of materials balance and environ-
mental fate analysis, since these efforts are often needed to estimate
exposure of humans to pollutants.

     The exposure of humans to pollutants and the potential effects of
this exposure should be considered simultaneously.  The rationale for this
is straightforward—unless an individual or groups of individuals are ex-
posed co a pollutant, they are not at risk of experiencing adverse effects,
even if the pollutant is thought to be capable of inducing serious effects.
Similarly, a pollutant known to produce no significant effects on humans
probably presents no substantial risk to humans even though there may be
widespread exposure.  Thus, the risk to various populations and subpopula-
tions depends upon the combination of exposure of those populations to a
pollutant and the related effects of the pollutant.

     As was the case with other parts of risk analysis,  the comprehensive-
ness of the exposure and effects analysis is determined by the quantity
and quality of available data.  In general, even for pollutants that have
long been recognized as toxicants, data on human effects, animal studies
or epiderniological studies, are expected to be more readily available
than are data on exposure.  For recently identified toxicants, both effect?
and exposure data are likely to be unavailable,  and extrapolations  or esti-
mates based upon other pollutants may be necessary.  Thus it is extremely
rare that both the potential for effects and exposure are thoroughly docu-
mented.

     The general questions that need to be addressed in examining the
available data on exposure and effects are as follows:

     (1)   Is there evidence of actual exposure,  i.e.,  monitoring data?

     (2)   Are the data available to estimate exposures  of the general
          population?

     (3)   Do the data indicate the existence of  subpopulations receiving
          higher exposures than the general population?
                                  7-1

-------
     (4)   Are there documented  haman effects  (tests,  accidental exposures,
          occupational health studies)  or must  extrapolation from labora-
          tory animal studies be made?

     (5)   Are there sufficient multi-species  animal tests  to permit
          reliable extrapolation of the results to  humans?

     (6)   Can evidence of exposure and  adverse  effects  on  humans be
          validated from epidemiological studies and  extrapolated to
          other exposure situations?

     (7)   Are there significant differences  in  human  effects for differ-
          ent subpopulations?

     In addressing the exposure of humans, one  should bear in mind the
initial sources of the pollutant and the fate and transport mechanisms
that determine the magnitudes and routes of  exposure,,  Only when exposures
are related back to pollutant sources will it be possible  to consider the
alternative actions—regulatory and control—that could reduce the poten-
tial or actual exposure.  Therefore, all possible exposure pathways and
all of the environmental media responsible for  the exposure should be
carefully delineated.  Both occupational and general  exposure should be
considered, bearing in mind exposure routes  of  inhalation, ingestion, and
dermal contact.  Specific subpopulations with higher  than  average exposure
should be identified—these subpopulations may  be delineated by geography,
age, sex, occupation, food consumption  patterns, activity  patterns, etc.
Identifying exposures in this manner requires heavy reliance on the mate-
rials balance and environmental fate portions of the  risk  analysis, since
these elements may be the basis for estimating  environmental concentra-
tions at various locations where humans can be  exposed, especially if no
monitoring data are available.

     To some extent, the exposure analysis should reflect  the nature of
effects.  For example, if a pollutant is well studied and  has been shown
to induce effects in laboratory animals at relatively high exposure
levels, worst case scenarios can be constructed for exposure in order to
differentiate the low degree of risk at more realistic  exposure levels.
Thus, the efforts devoted to identifying and quantifying exposures of sub-
populations might be reduced.

     In evaluating the effects cf pollutants on humans, one should con-
sider chronic functional disorders of various organ systems, as well as
the more often evaluated effects such as carcinogenicity,  mutagenicity,
and teratogenicity.  Chronic effects need to be emphasized since environ-
mental exposures  for most chemicals  (except perhaps  those  in the workplace
or resulting from accidental releases of chemicals) occur  over a long
period of  time, often at low exposure levels.  To some extent, the human
effects portion of an integrated risk analysis  can be performed indepen-
dently of other portions, since it depends upon the  results of detailed
laboratory  investigations or epidemiological studies rather than on
estimates of environmental loadings  or pathways.

-------
7.2  GOALS AND OBJECTIVES

7.2.1  Human Exposure Analysis


     The goal of human exposure analysis is to identify and quantify the
exposure of the general population and selected subpopulation groups to
a pollutant or family of pollutants.  Ideally the specific objectives
include:


    (1)  Determination of the exposure of the general population to the
        pollutant.   The general population is meant to represent the
        "typical" exposure,  if such a population group can be defined
        for a given pollutant.  The following parameters must be identi-
        fied :


        •    the source of the pollutant resulting in the exposure;

        •    the routes of exposure—e.g.,  ingestion inhalation and/or
             dermal contact;


        •    the duration and  frequency  of  exposure—e.g.,  continuous,
             1 hour per week,  1 hour per day,  etc.;


        •    the amount or extent  of exposure—e.g.,  the consumption
            as  a function of  respiratory flow, amount absorbed! etc.;

        •   the size  of the population  exposed.

    (2)  Determination  of the exposure  of  the work  force  to  the  pollutant
        in  terms  of:


        •    occupations  in which  exposure  is  encountered,  the  geo-
            graphical  locations and/or  types  of facilities and opera-
            tions;


       •    the numbers  of workers  exposed and their characteristics	
            age. sex,  etc. ;


       •    the source  of the pollutant, the route of exposure, the
            duration and  frequency of exposure,  and the dose or dose
            rare as indicated above;


   (3) Identification of specific subpopulation groups that experience
       a higher exposure to the pollutant than the "typical" person.
       These subpopulations may be identified by geographic location,
       size, age, sex, dietary or activity patterns." The parameters'
       of such exposure would  be the same as those indicated above.
                                  7-3

-------
7.2.2  Human Effects Analysis

     The goal of human effects analysis is to identify and characterize
the health effects in humans that may occur as a result of exposure to
a pollutant.  More specific objectives include:

    (1) Examination of the distribution, metabolism, bioaccumulation,
        and excretion of pollutants in humans and laboratory animals
        in order to identify target organs or systems.  In addition, it
        is desirable to identify the underlying mechanisms responsible
        for the effects of pollutants in humans and the relationships
        between exposure level (dose) and response in various species.

    (2) Determination of the acute and chronic health effects on humans
        expected and/or observed to occur from occupational or accidental
        exposures and the exposure pathways and levels that result in
        these effects.

    (3) Determination of the known acute and chronic health effects of
        pollutants on humans on the basis of epidemiological studies
        and the exposure pathways and levels that result in these
        effects.

    (4) Consideration of the acute and chronic health effects that may
        be expected to occur from exposure to pollutants, based upon
        review of laboratory animal studies, in vitro and in vivo
        studies with mammals, test organisms, tissues, cell cultures,
        or other biota.  Extrapolation of the results to humans may be
        possible in some cases.

    (5) Estimation of the "no-effect" levels of the pollutant for various
        exposure pathways, based on animal data or human data, when
        available.

The information obtained in the effects analysis should ultimately be
presented in a form that can be combined with exposure analysis for tha
purposes of considering the risk to the general population or specific
subpopulations associated with the pollutant.
7.3  APPROACHES AND METHODS

7.3.1  Exposure Analysis

7.3.1.1  General Approach

     Identifying and quantifying the exposure of the general population
and the subpopulation groups is a difficult task, complicated by un-
certainties and lack of data, ar.d requires numerous assumptions and new
and often unproven estimation techniques.  Hoxvever, Ln order to estimate
the range of risks presented by a pollutant, some "informed" estimate
                                  7-4

-------
of exposure must be made and  this requires  taking a  systematic  and  compre-
hensive approach to analyzing the best available data.

     The exposure analysis builds upon concepts and  data  from the materials
balance, monitoring data, and environmental fate analysis.  The  basic
steps  in exposure analysis are as follows:

     (1)  Identify, as comprehensively as possible,  all potential
          sources of exposure of the human  population to  a chemical.
          In this context, "sources" can signify environmental media,
          human activities, or consumer products.

     (2)  For each source, identify the route of exposure associated
          with the source, e.g., inhalation, dermal  contact, ingestion.

     (3)  For each source and  route, identify key subpopulations based
          upon demographic/geographic characteristics that are expected
          to affect exposures.

     (4)  For each specific population group (e.g.,  general population;
          work force; specific subpopulation characterized by age,  sex,
          type of activity, location, etc.) and for  all possible routes
          and sources of exposure for each group, attempt to quantify
          the exposure as an  average daily uptake or some other parameter
          that may be related  to effects levels and  the numbers of  per-
          sons exposed.

     Arraying data and information on an exposure matrix such as the one
in Table 7-1 is a convenient way to organize this effort.  Beginning at
the left-hand side with the general population's exposure through the
three main exposure routes, the matrix shows in the columns to the  right
the steps taken to identify exposure routes and to characterize, first
qualitatively and then increasingly quantitatively,  the exposure situa-
tion and the exposure level.   When data permit, an attempt should be
made to estimate the amount of the pollutant intake actually absorbed
and to estimate as precisely as possible the size of each population or
subpopulation.   Depending upon the chemical, occupational exposures may
need to be considered in the same manner.   Special exposure situations
and scenarios may be identified in the materials balance,  environmental
distribution, or fate analysis because of  characteristics of sources or
environmental releases, geographic considerations arising from volume of
releases or intensity of sources, or unusual use situations.   Often
these scenarios are a further refinement of the more generalized exposure
routes  and need to be considered as  separate exposure routes.

     The subsequent discussion considers these  steps in assessing ex-
posures,  first  those leading  to the  identification of exposure  routes,
and then methods  for estimating exposure levels for  the  general  popula-
tion and subpopulations.
                                 7-5

-------
                                                                TABU; i-\.  EXPOSURE MATRIX
   t'opul a t-i on

Central
                          Route
                  IngestIon
                  Inhalation
                  Uermal Absorption
Oceupat lonal      Ingest Ion
                  Inhalation
                  Dermal Absorption

Special Situations or Scenarios:

spl 11s
use of special products
II vi! near disposal situ or oouicfc
 Subpopulation/Associated
	Source

Drinking water
  typical
  maximum

Food
  typical
  max Ituuin
Urban—
  typical
  maximum
Rural—
  typical
  maximum

Water—
  typical
  maximum
                                                                        Concentration Exposure   Exposure
                                                                             in Medium
Constant


Adult —
 2 liter per
 day
Children—
 1 liter per
 day
                                                                                                  child
                                                                                                  4 m-Vday
                                                                                                  adult
                                                                                                  20 m /day
Exposure
Duration/   Calculated   Absorbed  Size of
Frequency   	Intake      Dose     Population

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7.3.1.2  Sources of Exposure, Exposure Routes, and Subpopulation Groups

     Sources of exposure include media, products, or activities that
result in human exposure.  This concept can best be explained by example.
Consider a chemical that is used in household detergent.  Direct exposure
could result from contact with, or inhalation (perhaps even ingestion)
of, the product itself.  Indirect exposure could result from contact
with the water solution in which the detergent is used, by contact with
the residual detergent on the clothing or material washed in the deter-
gent, by inhalation of vapor from the mixture, or by ingestion of the
residual detergent from food placed on dishes washed with the detergent.

     Thus, direct and indirect use of the chemical or pollutant must be
considered  along with the routes associated with  exposure to the general
population.  In identifying these exposures, several general exposure
sources—related to environmental media—must be considered:  ambient
water, drinking water, ambient air, and food.  Pollutants that nay exist
in these media may not be attributable to specific sources, but rather
to an aggregation of "sources," which yields a distribution of the chemi-
cal in the environment.  The approaches and methods used in environmental
pathways and monitoring are, in fact, designed to describe or develop
this "ambient" media distribution.  The source/exposure combinations in-
clude the background level of exposure for the general population in
addition to exposure of subpopulations in specific areas or engaged in
specific activities.  For example, although an average general exposure
resulting from ingestion of food containing a pollutant might be develop-
ed from average diet considerations, exposure of special subpopulations
who eat large amounts of meat, freshwater fish,  milk, etc., must be con-
sidered.

     The identification of subpopulations should be approached in several
different ways in order to ensure a thorough examination of exposure.   In
the discussion of the materials balance analysis, activities such as ex--
traction, refining,  manufacture, transportation,  distribution,  storage,
use,  and disposal were defined; each of these has the potential for re-
leasing the chemical to the environment or perhaps exposing persons direct-
ly.  As an example,  disposal operations,  both of  products and "in-plant"
materials,  must be examined for the variety of exposures and routes.
Exposure might result from material disposed in  a chemical waste  facility,
perhaps indirectly through the ambient air environment  of the site  or
surrounding public water supplies,  with possible  exposure routes  including
inhalation,  contact,  or ingestion.   Another source may  be the "municipal
dump" or transfer station at which exposure of the public could result
through contact with empty containers  (with residual  chemicals),  or by
inhalation  of  dusts  or particulates.

     Thus,  all of the steps in the life cycle of  the pollutant should  be
considered in order to determine the potential for human exposure.   The
purpose of reviewing these steps is to tie exposures to specific sources
of the pollutant and to define subpopulations who sustain exposure
                                  7-7

-------
levels greater than those of the general population.  These sufapopula-
tions may be subject to occupational exposures, may live, work in, or
frequent areas of pollutant sources, or obtain drinking water from
supplies contaminated by pollutant sources.

      Both  the  consideration of  ambient  pollutant levels  to which  the
general  population may be exposed and the  review of pollutant sources
are  required for  identifying subpopulations exposed.  Identifying the
potential  exposure of specific  subpopulation groups with unusual  and/or
narrowly defined  characteristics is a difficult task and requires care-
ful  consideration.  Furthermore, characterizing the populations and ex-
posures  quantitatively in subsequent steps of  the exposure analysis is
often not  possible because data are lacking on the size of the popula-
tion or  the exposure level.  Nevertheless, it  is important to attempt to
identify these subpopulations and to estimate  the range of possible
exposures, so  that the range of risks (exposure combined with effects)
can  be estimated.  Furthermore,, differentiating the risk of exposure to
subpopulations from those of the "average" population may identify the
types of control  strategies needed to reduce overall exposure and risk
associated with the pollutant.

      The complexity of the sources, exposure routes, and subpopulation
groups and the effort devoted to identifying them will vary with  each
exposure/risk assessment, and will depend upon the pollutant in question
and  the  purpose of the assessment.   In some cases,  it may be sufficient
to consider only  the "workplace" exposure, the general population exposure,
or exposure of a  single subpopulation group; in others,  it may be
necessary to identify sources, routes,  and groups to the fullest  extent
possible.  In determining what is reasonable and appropriate in each
case, one should bear in mind several key points:

      (1)  that the risk will be a function of both exposure and the
          effects and,  therefore, in-depth analysis of exposure may not
          be warranted  if human, health  effects are not of concern;

      (2)  that the effort to quantify exposure with precision may be in
          vain if health effects are not well established or the back-up
          data for exposure lack precision; and

      (3)  that  the effort should be focused on the  combination of  sources,
          routes,  and population groups  that have  the  potential  for highest
          total exposure.

7-3.1.3  Exposure Levels  From Major Exposure Routes

     After exposure sources,  exposure routes and  population subgroups
have been identified,  the next step is  to characterize the  exposures
quantitatively  for each source-route-population group  combination.  For
                                  / -o

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simplicity, this process can best be described by consideration of the
major exposure routes—inhalation, ingestion, and dermal contact—as they
apply to the general population, workplace population, and special sub-
population groups.

     Inhalation

     Exposure of individuals by inhalation can often be estimated in a
straightforward way.  Data are available on the respiratory rate and
volume for individuals as a function of activity level (see Table 7-2).
Once these parameters have been established, ambient concentrations need
to be established.  Usually, monitoring data do not allow the computation
of a statistically meaningful mean or median that would describe average
exposure to the U.S. population.  If data were adequate,  however, such a
value could be used.  Generally, it is more useful to consider the data
available, their geographical and source-related representation, and
choose a "typical value."  Although this method requires judgment, it
can provide a more meaningful value for typical exposure.

     In addition to the typical exposure, or exposure to the general pop-
ulation, a maximum exposure should be established.  If a statistical treat-
ment is possible, the 95th percentile, or a similar value, may be chosen.
Otherwise, the data must be evaluated to determine what this value might
be.

     If monitoring data do not exist, estimates based upon anticipated
release rates and simple air models will be required.  Depending upon
the materials balance and fate studies, estimates of ambient concentra-
tions may be on a national, regional or more localized basis.  Similarly,
OSHA, NIOSH. cr other agencies may have available monitoring data or
methods of estimating concentrations in the workplace.

     Determination of atmospheric concentrations of a pollutant to which
special subpopulation groups are exposed may be difficult; however,
monitoring data may exist for selected materials and exposure situations—
for example, urban and rural environments,  agricultural areas in which
pesticides have been applied,  areas near production facilities,  and other
industrial sources.   Usually,  however, air concentrations of pollutants
associated with special exposure sitautions will have to  be estimated.
These estimates would normally be accomplished in environmental fate and
pathway analysis and would be based upon the specific process or activity,
quantity of pollutant, its chemical and physical characteristics,  and
environmental factors such as wind, rain,  temperature,  etc.   Persons
located near smelter operations, cooling towers,  waste disposal sites,
or commercial cleaning facilities are examples of special groups for
which exposures may need to be evaluated.

     Another source of inhalation exposure  that may be important in  some
situations is inhalation of water vapor or  fog (mist,  droplets),  which
has evolved from a water stream containing  a pollutant.   For these
situations,  estimation of the concentration of pollutant  vaporized inco
                                   7-9

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             TABLE  7-2.  RESPIRATORY VOLUMES FOR HUMANS  ENGAGED
                         IN VARIOUS ACTIVITIES
Time Reference and
	Activity

Per minute:

  Resting
  Light Activity

Per day:

  8 hours of working
    "light activity"

  8 hours of nonoccupa-
    tional activity

  8 hours of resting
     Total 24 hr
                                      Air Volume  (liters)
Adult
man
Adult
woman
Child
(10 v)
Infant
(1 v)
Newborn
  7.5
 20.0
 6.0
19.0
 4.8
13.0
1.5
4.2
0.5
1.5
 9,600    9,100    6,240     2,500      90
                             (10 h)    (1 h)
 9,600    9,100    6,240


 3,600    2,900    2,300     1,300     690
          	    	     (14 h)    (23 h)
2.3xl04  2.1xl04  l.SxlO4   0.38xl04  O.OSxlO4
Source:  International Commission on Radiological Protection (ICRP).
         Report of the Task Group on Reference Man.   New York,  NY:
         Pergamon Press;  adopted  October 197^.

-------
 the  air  space  above  the  water source,  or  the  pollutant  concentration  in
 the  mist or  fog  (suspended  water droplets), must  be  estimated.   Again
 physical/chemical  properties  of  the  pollutant,  concentrations  of pollu-
 tant in  the  original water  stream, and environmental  parameters  will  be
 important  in these estimates.  Approaches  to  making  these  estimates have
 been developed by  the  U.S.  EPA (Adamson e_t. al_.  1979).

      Once  the  air concentrations  have  been established  to  the  extent
 possible  for each situation,  this information can be  combined with the
 appropriate  respiration  rate  to  determine  the estimated exposure  level.
 The  general  methods will yield estimates of the quantity and rate of
 pollutant  inhaled by various  population groups, e.g., g/day, mg/hr, etc.
 Consideration  of the source,  route and  characteristics of  the exposure
will  determine whether the  exposure  is  intermittent or continuous, short-
 er long-term,  and whether it  is a one-time exposure or an  average intake
 over  some  time period.

      The procedure described  above considers  potential  exposure  to a
 pollutant.   However, much of  the  pollutant inhaled may not be  absorbed
 into  the blood stream.   Therefore, before  exposures can be compared with
 effects  levels and the risks  presented  by  these exposures  assessed, one
 needs  to  know  how much of the material  that is  inhaled is  actually ab-
 sorbed in  humans as compared  to  laboratory animals.   An evaluation of
 rates  of  absorption and metabolic pathways is conducted in conjunction
 with  the  human effects analysis  (see Section  7.3).  Often, though, the
 available  data are not sufficient to indicate what portion of  the poten-
 tial  exposure  is actually available  to  the body.  In  these cases, it  is
necessary  to assume,  as the worst case, total absorption.

      An  example of inhalation exposure estimates is provided in Table
 7-3,  which gives ranges of  exposure levels for trichloroethylene in
 different  environmental scenarios (Thomas et_ al. 1981).  The atmospheric
 concentrations are maximum  reported values in the vicinity of the two
major sources  of atmospheric  releases  (TCE manufacturing facilities and
degreasing sites) and reported ambient levels for other areas.   A total
daily intake has been estimated for each of these exposure situations
on the basis of estimated durations of inhalation exposure and standard
respiratory volumes for humans (in Table 7-2).

     Ingestion of Food and Drinking Water

     The most widespread exposure to pollutants for the largest number
of people will probably occur through the ingestion of food and drink-
ing water.  As a result,  it will be important  to consider each  of these
ingestion routes carefully and assess exposure to the general population
ar.d specific subpopulation groups.  In general,  the exposure to the work-
place population from food and drinking water  will be similar to that  of
the general population so that this subpopulation does not  need to be
considered separately for this exposure route.
                                 7-11

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                  TABLE 7-3.  EXAMPLE OF  ESTMATED INHALATION  EXPOSURE TO T1UCULOROETHYLENE
     . ion
          '
Maximum  Observed
Concentration
      H/m  )
                                                                   Weekday Dur-
                                                                   ation of
                                                                    (hrs/tlav)
 Nea r fianufac! uri n;  S i I .

   Urban - Day  (ne.;r  i

          - Nij->bl  (Havoiin.-,  N.l)

   llnial - Day  (luar  I'l.iiiul a." t urei )

          -- Nijihl  (lal Jedej-a Nat. Forest)

 Near De}« leas in)- Sites

   I'rban - Day  (Ai rural i  Factory)

          - Kij-.ht  (llayi.inu-,  N.I)

   Kural - |i iy  (Ail craft  Factory)

          - Nij-.lit  0'aUede.ya Nat. Forest)

 Low  Arnl.ieui  - Rural (Talledcya Nat.  Forest) or
               Urban (East Coast)
Estimated
Total
J440
47
.1440
3
23.
47
23 S
3
3
8
16
8
J6
8
16
8
16
24
14
0.6
14
0.04
2.3
0.6
2. J
0.04
0.06
             I 4 .04
                ..  (Ainl.ieiH  Uackj-rouiuJ)
                                                                                        0. ()()()()
   Concentration estimates are  taken from Table 4-5  in source cited below.

   Weekend  exposures will be  24  hr/day at night time  levels.  Hence,  these  values provide  an upper-
   bound  estimate daily on exposure levels.
   m.u,/      BaaUd  °n  rca'llralil>n °f 1'2 ll)3/^- (awake), 0.4 ,n3/br (sJeeping),  about 20 fl,3/day
   (K.HP  1975).   (See citation below.)

Source:  Thomas,  R.  et al.  An exposure and risk assessment for tricbloroethyleue.  Final  Draft Report.
         Contract EPA 68-01-5(J49.   Washington. Oil:  M.m i I or i nt- ;md Ibir;i  Sisnnnrl  niui^i^,-.   nfl !,... f^f

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      Food

      The ideal data for estimating human exposure through ingestion of
 food are residues in various cooked and/or processed foods included in
 the American diet, and food consumption patterns of the general popula-
 tion and subpopulation groups.   After the food consumption patterns
 for various subpopulations have been identified, the food residue data
 can be used to determine quantities of pollutants ingested.

       The  closest  approximation  to  this  ideal  is probably the  Total Diet
 Studies  conducted  by  FDA,  Bureau  of  Foods  (U.S.  FDA  1977).  In  these sur-
 veys,  residues  of  certain  chemicals  in  specified  food groups are analyzed.
 Composite samples  are used for  these food  groups; residues in individual
 foods  are not available.   The Total  Diet  Studies  consider primarily the
 diet of  a 16-19-year  old male for calculations  of dietary intake.  The
 pollutants  considered by FDA are  primarily metals and pesticides, and.
 comprehensive information  for many organic chemicals is lacking.  Thus,
 these  data  are  useful  primarily for  initial estimates of the total amount of
 a  pollutant ingested  by average populations consuming standard  food groups.
 They do  not generally identify  specific foods with contamination problems,
 or population groups  with  high  consumption.

       In the absence of data from Total Diet Studies, or perhaps in addi-
 tion to  it,  data on specific cooked  or processed  foods are desirable.
 Information on  residues in all  food  groups is rarely available.  Thus for
 any given pollutant,  two options  are available;  the  first is to determine
 if the available information is an adequate representation of what might
 be expected in  the  whole diet;  or second,  to make assumptions about what
 might  be expected  in  other  foods  based on the fata of similar chemicals.
 For example, residue  data  are often  available for fish as the only food
 item.  Since bioaccumulation may  have occurred, it may be reasonable in
 these  cases  to  assume  that  fish constituce a major dietary exposure route
 for humans.  For example,  in developing ambient water quality criteria,
 the EPA assumes an  average  daily  consumption of 6.5 g of fish,  utilizes
 bioaccumulation data  to estimate  the amount of pollutant contained in that
 amount of fish, and combines this dietary intake with drinking water in-
 take to establish a total  intake  of water-related pollutant (U.S. EPA 1980).
 One should, however,  consider whether additional major food exposure routes
 exist  other  than fish.  For example, there may be some specific studies
 on residues of  pollutants  in meat and poultry, where contamination problems
 are expected to occur.  Sources such as these should be reviewed to deter-
mine the existence of data potentially applicable to the pollutant  in  question.

       Rarely, however, is  information available on residues  in cooked or
 processed food; residue studies in raw foods are much more common.   Pollu-
 tant concentrations from raw food cannot easily be extrapolated to those
 in cooked foods.  The U.S. EPA has been grappling with this problem in
 setting tolerances for pesticides in food and has not yet determined a
 satisfactory way to extrapolate from data concerning residues  in raw foods.
At present,  tolerances are set on the basis of raw food.
                                   7-13

-------
     In the absence of specific residue data for food, materials balance
and fate considerations may be able to provide some insight into the
probability that a pollutant will occur in food.  Data are scarce on
such things as pollutant concentrations in soil, uptake rate from soil,
bioconcentration by plants and animals, and it is unlikely that accurate
concentration levels in raw foods could be estimated.,  Furthermore, models
would still be required to determine the changes in pollutant concentra-
tions in foods during processing and preparation.   Thus,  except for
some pesticides and metals,  only scattered data on isolated raw or
prepared food items are likely to be available, and in some cases no data
will be found.  Unless the food items for which data are available repre-
sent the major source of dietary exposure, even these scattered data will
be of limited use in an exposure or risk assessment.

     Once the data to be used for food contamination have been identified
or estimated, consumption patterns must be established.  The Agricultural
Research Service of the USDA conducted extensive food consumption survevs
in 1965 and 1978 (USDA 1972, 1980).   These surveys include average con-'
sumption patterns by age groups and geographic regions.  Other surveys
conducted by the USDA contain some information pertaining to food consump-
tion; data on consumption of fishery products  and food fats and oils from
a survey by the Economics,  Statistics, and Cooperatives Service (USDA
1976) are shown in Table 7-4, as an example of the type of data that are
available.   While data from USDA surveys are extremely useful for estimat-
ing ingesticn exposures,  they do not provide information on variation in
consumption by different age group or populations in various geographic
regions.  In addition,  they may not provide consumption data for a specific
food item of interest,  for  example,  peanut butter.   Thus in many cases,
assumptions must be made about food consumption in order to estimate
typical or maximum intake of a specific food item.

     Despite the numerous limitations described above,  the following
process may be followed in  attempting to determine the exposure to pollu-
tants through food ingestion.

     (1)  Examine the USDA/FDA Market Basket/Total Diet Studies to deter-
          mine if the pollutant has  been measured  as part of  a  specific
          or general study.   Use values obtained  as  an indication of
          general exposure  through food ingestion.

     (2)  Review any specific studies  related  to  the pollutant  in terms
          of residues or  tolerances  and,  on the basis  of  food consumption
          and diet information,  determine the  exposure  through  ingestion
          of those specific  foods.   Project, if possible,  the ingestion
          of the pollutant  from similar foods  and/or the  total  diet.

     (3)  Through literature research,  analysis of monitoring data,  en-
          vironmental fate  considerations,  analogies to other pollutants
          and products,  or  simple  models,  determine  the concentration
          (range of concentrations)  of the pollutant in the  food  or  food


                                  7-14

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        TABLE 7-4.  PER CAPITA CONSUMPTION OF FISHERY PRODUCTS
                    AND FOOD FATS AND OILS IN THE U.S., 1976
               Fish
 Item
 Fresh and Frozen
   Fish
   Shellfish
     Total
                        Per Capita
                        consumption
                        (pounds in 1976)
                   5.5
                   2.6
                   8.1
                                           Food Fats and Oils
Item
Table Spreads

  Butter
  Margarine

     Total
                                                     Per Capita
                                                     consumption
                                                     (pounds in 1976)
 4.4
12.5

16.9
 Canned

   Salmon
   Sardines
   Tuna
   Shellfish
   Other
    Total
                   0.
                   0.
                   2.8
                   0.4
                   0.4

                   4.3
Cooking Fats
  Lard
  Shortening
    Total
 2.8
18.2

21.0
Cured

TOTAL ALL FISH
                  0.5

                 12.9
 Edible weight
Source:
U.S. Department of Agriculture (USDA).   Food consumption.
prices, expenditures.   Agricultural Economic Report No. 133
Supplement for 1976.   Washington, DC:  USDA; 1976.
                                  7-15

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           group under consideration.   (Often  the many uncertainties  in-
           volved will make  this very difficult  if not impossible.)   If
           feasible,  combine these  estimates to  obtain daily  intake of
           the pollutant  for the various subpopulation groups.

      (4)   Through consideration of the materials balance of  the pollutant
           and uses of the products that contain the pollutant, develop a
           list of specific  activities or scenarios that could result in
           localized occurrence of  the pollutant in food:  e.g., use as a
           pesticide on selected products, as a preservative, in a food
           packaging material; discharge to a freshwater stream from which
           people catch and  eat fish; movement through the foodchain to
           mother's milk; processing into a one-of-a-kind food product,
           etc.  For each scenario,  attempt to identify the subpopulation
           group by age,  sex, location,  habits, etc.,  that may be exposed.

      (5)   Consider changes  in concentrations or residues of pollutants
           in food processing and preparation.   Although it is not possible
           to evaluate these changes thoroughly, they  need to be addressed
           at least qualitatively in the estimation of exposure, especially
           in cases where levels of a pollutant in food may actually be
           increased during processing (e.g., the addition of lead to foods
           from lead solder  in cans).

      (6)   Combine, wherever possible,  data on average daily intake and
           exposure for the general population with data for specific sub-
          populations to establish ranges of human exposure.

     In performing the last few steps  given above,  there are a number of
scenarios  (activities)  that are more or less routine  for each pollutant
or product in which the  pollutant may  be a contaminant and each scenario
may represent an exposure situation that should be  analyzed as a separate
exposure route:

     (1)  use as a pesticide or fertilizer,

     (2)  use as a food  preservative or additive,

     (3)  use in food processing  or preparation activity,  including
          equipment,

     (4)  use in a food  container  or packaging material,

     (5)  release  into soil or  water from  which food  or  food crops are
          grown,

     (6)  release  in  the vicinity of grazing or rangeland,

     (7)  use in an animal  food or  feed  or packaging  thereof,
                                  7-16

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     (8)  use in water system for food washing or preparation,

     (9)  release into water systems in which fish, shellfish or other
          wildlife live or feed, and

    (10)  use as a supplement in a poultry or livestock feed.

     Through systematic consideration of each opportunity for exposure
the total exposure of humans to pollutants through food ingestion
may be estimated.  Clearly this is an area of risk assessment that needs
considerable research, development and evaluation.

     Table 7-5, 7-6, and 7-7 give examples of the results of analyses of
exposure from food ingestion.  The data have been developed and presented
in different ways.  In Table 7-5, the ingestion of di(Z-ethylhexyl)
phthalate was calculated on the basis of data on concentrations found in
various food items, and the levels of consumption of these items (Perwak
e_t al. 1981a) .   Although these foods obviously do not represent a total
diet, it was felt that they were a close approximation of total dietary
exposure since high fat items were sampled in which phthalate esters
might be expected.

     Table 7-6 shows the dietary intakes of copper reported in the litera-
ture (Perwak et_ al. 1980a) .   In this case, a separate analysis was not
conducted for two reasons.  First, as is evident from Table 7-6 a con-
siderable amount of work has been done in this area, and the results are
in agreement.  Second, the low order of copper toxicity to humans suggested
that dietary intake would not be a significant source of risk.  Thus, a
great degree of accuracy in estimating dietary intake was not required.

     Table 7-7 shows the estimated dietary intake of mercury by a select
subpopulation,  fish eaters (Perwak et al. 198Ib).  Again, intakes were
calculated through use of consumption data and general residue data for the
same fish species.  The results show that an increased consumption can
substantially increase intake over that of the population average, which
in this case was about 3 ug/day attributable to seafood.

     It is important to point out that a relatively large amount of data
were available for analysis of the pollutants in the examples given above.
Since this is often not the case, the possibility for detailed considera-
tion is reduced.  In some cases, quantitative estimation of dietary intake
is not  feasible, although intake can often be compared qualitatively with
other exposure routes.

     Drinking Water

     Exposure of humans to pollutants through drinking water can vary
widely, even within a very localized area, depending on the water supply.
The ideal information for estimating exposure through drinking water would
include a distribution of concentrations of the chemical in drinking water.

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 TABLE 7-5.   EXAMPLE OF ESTIMATED 1NGESTION EXPOSURE OF DI(2-
             ETHYLHEXYL) PHTHALATE VIA SELECTED FOOD ITEMS
                 Average Daily         	Intake  (mg/dav)
Food Consumption3 (g/day) Average
baked beans
corn meal
canned corn
white bread
eggs
cereal
meat
margarine b
processed American
cheese °
milkc
fish
Total
7.0
9.6
7.1
12.0
43.5
37
210
15.5
13.3
230
21.4

trace
0.002
trace
0.01
0.004
0.01
0.13
0.03
0.02
0.04
0.004
0.25
Maximum
0.01
0.02
0.001
0.14
0.03
0.13
0.63
0.69
0.12
0.14
0.15
2.1
 Please note that some of the categories of foods for consumption volumes
 do not exactly match the categories of sampled food items in all cases.
 For example, consumption data are used for all meat, bread rolls, and
 biscuits; however, only certain food items within these general categories
 were sampled for DEHP.   No estimate of consumption was found for baked
 beans, so 7.0 g/day was assumed.

 Consumption of chese foods has been corrected for fat conten"-
 margarine, 30% fat; cheese, 25% fat; and milk, 2% fat.
Source:
Perwak, J., e_t al.  An exposure and risk assessment for phthalate
esters.  Final Draf-: Report.  Contract EPA 68-01-3857.
Washington, DC:  Monitoring and Data Support Division. Office
of Water Regulations and Standards,  U.S.  Environmental
Protection Agency; 1981.
                                7-13

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                TABLE  7-6.  EXAMPLE OF  INGESTION  EXPOSURE  ESTIMATES
                            FOR COPPER  BASED ON TOTAL DIET STUDIES
 Intake
 (mg/day)

  0.34
  0.91

  1.0


  1.04

  1.2


  1.5


  1.8-2.1

  1.9


  2.4

  3.8

  7.6
      Type  of  Diet

      self-selected
      (24-hr)

      self-selected

      self-selected


      self-selected

      Non-institutional
      diets

      diets (no liver)


      balance study

      institutional
      diet

      self-selected

      diet composites

      diets  (with liver)
 Number of
 Subjects
Reference
  4 female    White  (1969)


  1 female    Tipton et_ al_. (1966)

 11 male,     Holden et al. (1979)
 11 female

 36 female    Tipton e_t al. (1966)

 12 female    Guthrie and
              Robinson (1977)

 12 female    Guthrie and
              Robinson (1977)

 11  female    Robinson e_t  al.  (1973)

 12  female     Guthrie  and
              Robinson  (1977)

 12  female     Guthrie  (1973)

 1 male      Zook and Lehman  (1965)

11 female    Guthrie and
             Robinson (1977)
 See source indicated below for references.
Source:
Perwak, j. et_ al.  An exposure and risk assessment for copper.
Final Draft Report.  Contract EPA 68-01-5949.  Washington  DC-'
ilomtonng and Data Support Division, Office of Water Reo-ula-"
tions and Standards,  U.S. Environmental Protection Agency- 1980
                                  7-19

-------
                       TAIJLE 7-7.  EXAMPLES OF 1NCESTION EXPOSURE ESTIMATES
                                   OF MERCURY FOR A SPECIFIC SUBPOPULAT10H
Mercury
                                                                        Upper Limit
                                                                        Daily Intake
                                           Serving/
 Assumes a 0.5 Ng/g mercury action limit.
Concentration    (Pg)a - 95%
                 Confidence
                 Limi ts
                                                                           51.37
Person Sjiecies g/Serving
Person L Pike
Uass
Perch (marine)
Not identified
i
hO
o
Person 2 Pike
Bass
Perch (marine)
206
167
144
150



253
218
181
Month
15
3
2
1



19
4
2
Av£. Max.
0.0]
0.75
0.13




0.01
0.75
0.13
1
2
0




1
2
0
.7
.0
.59




.7
.0
.59
                                                                            79.46
Maximum Jntake

      141
                                                                                                      a
                                       222
Source:   Perwak,  .1. et al.  An exposure and  risk assessment  for  mercury.   Final  Draft  Report.   Contract
         EPA 68-OJ-5949.   Washington, DC: Monitoring  and Data  Support Division,  Office of  Water
         Regulations and  Standards, U.S.  Environmental  Protection Agency;  1981.

-------
comprised of data from enough locations to be representative, and the
corresponding numbers of persons exposed to each concentration range.
Unfortunately, this ideal situation rarely occurs.


     Monitoring data for drinking water are more generally available
than data on pollutant levels in air or food, but do not provide a com-
prehensive view of the many waterborne pollutants that may be found in
water supplies throughout the U.S.  The most extensive monitoring of
drinking water was conducted in 1970; the survey sample in this study
included 6595 water supplies in the U.S., including well water, ground
water, surface water and tap water (U.S. DREW 1970).  However, the only
parameters considered were those regulated by the 1962 USPHS standards.
More recently, in 1974, EPA conducted the National Organics Reconnaissance
Survey (NORS) (Symons et_ al_.  1975); this study sampled 80 water supplies
in the U.S.  for halogenated organics.   In 1976,  EPA conducted the National
Organics Monitoring Survey, which looked at levels of a large number of
organics in 112 locations in the U.S. (U.S. EPA 1978a).  These data com-
prise a partial basis for assessment of national exposure.  Since 1976,
a number of additional studies'have been conducted, usually in specific
locations or for specific water supplies.

     The monitoring studies described above can sometimes provide data
to estimate the distribution of the chemical in drinking water over the
U.S.  Populations can be associated with the water supplies sampled and
with ground water and surface water in general,  but the extrapolation of
Che distribution to the total U.S. population is not generally possible
with the data available.

     If sufficient data on the pollutant concentration in drinking water
are not available on a national scale, localized data may be used in one
of two ways.  If data are available for a location where high concentra-
tions would be expected on the basis of materials balance" and environ-
mental fate considerations, the subpopulation of residents in the loca-
tion can be identified and their exposure estimated.  In this case,  no
estimate of exposure to other suhpo-pulations can be made.  If the data
are not from a local "hot spot," they might be used to validate the re-
sults of model(s), which would then be used to estimate maximum concentra-
tions in drinking water in other locations.  Modelling of pollutant  fate
in surface water is more highly developed than for groundwater.   Hence
this approach is more likely to be useful for estimating exposure via
drinking water from surface water supplies.

     In many cases and for ;nany locations,  however, monitoring data  for
raw or treated drinking.water are unavailable or inadequate for purposes
of exposure assessment.  For a worst case consideration,  ambient concentra-
tion data (measured or estimated from materials  balance and pathways
analysis) may be used directly for chemicals that would not be formed
during water treatment or encountered in the water distribution system.
If a more precise analysis is needed,  losses or  additions during water
treatment must also be considered.  (See chapters on Monitoring and  Fate.)
                                  7-21

-------
     The steps involved in estimating pollutant exposure of general and
specific subpopulations from drinking water include:

     (1)  Review appropriate national surveys, STORE! data, and EPA
          regional data to develop appropriate national average values
          and concentration ranges of the chemical and number of persons
          exposed to the chemical, if possible.

     (2)  Consider local data from appropriate municipal water districts,
          surveys, etc., to determine local concentration levels and to
          generalize to national average levels if practicable.

     (3)  From materials balance and environmental fate considerations,
          identify any localized areas and pathways that might result
          in contamination of drinking water supplies.  Through modeling
          efforts, and in comparison with available monitoring data, deter-
          mine whether these sources have led to contamination and at what
          levels.  To  the degree possible extrapolate these conditions
          to other locations and exposure levels.

     (4)  If no  (or limited) data are available on drinking water, con-
          sider  ambient water monitoring data for the pollutant (surface,
          ground, etc.) and investigate to what extent  treatment would
          remove the contaminant from the water in the  water supply/
          treatment process.

     (5)  From materials balance considerations, examine other unconven-
          tional routes of entry of  a pollutant into  drinking water;  for
          example, from chemicals used in treatment,  pipes/valves  used
          in  distribution systems, etc.  From monitoring data or simple
          models, evaluate the  concentrations  that may  result in drink-
          ing water.

     Once the concentrations of a pollutant  in drinking water have been
 determined  for various exposure subpopulations, they  must  be combined
 with an appropriate exposure constant in order to estimate the pollutant
 intake.  Although consumptions  of 2  liters per day  for  adults and  1 liter
 per day for children  are  commonly assumed  in exposure calculations,  con-
 siderable variation exists in consumption.   In cases  in which  ingestion
 via drinking  water  is  a major exposure route,  it may  be appropriate r.o
 consider a  range of consumption values in  estimating  exposures.   In addi-
 tion,  the rate  of absorption of the  pollutant in  the  gastro-intestinal
 tract  must  be considered  for pollutants  in drinking water  in the  same
 manner as for pollutants  in  food.

      Tables 7-8 and  7-9 illustrate  some  results  of  analyses of  drinking
 water  exposure.   Table 7-3  shows  the drinking water  exposures  for 1,2-
 dichloroethane,with associated  populations (Perwak  e_t al.  1982a) .   In
 this case,  as is common for many  organic chemicals,  the reported  values
 of the monitoring data are near the  detection limit  of  the analytical
                                   7-22

-------
   TABLE 7-8.  EXAMPLE OF ESTIMATED EXPOSURES TO 1,2-DICHLOROETHANE
               VIA DRINKING WATER INCLUDING POPULATION SIZE
Population

General Population

   Surface Water

   Ground Water
Estimated
Population
Size
5 million

5 million
 Assumption



 2 ygA, 2£/day

0.3 'Mg/i,  2£/day
Calculated
Exposure
(ug/day)
    4

    0.6
Isolated Sub-
Populations

   Surface Water


   Ground Water
               maximum level of
               4.8 Ug/£,  21/day

               maximum level of
               400 ug/i,  2£/day
    9.6


  800
Source:  Perwak et_ al.   An exposure and risk assessment for dichloro-
         ethanes.   Final Draft Report.   Contract EPA 68-01-5949.
         Washington,  DC:  Office of Water Regulations and Standards,
         U.S.  Environmental Protection  Agency;  1982.
                                 7-23

-------
       TABLE 7-9.  EXAMPLE OF MAXIMUM AND TYPICAL ESTIMATED EX-
                   POSURES TO TRIHALOMETHANES VIA DRINKING WATER
                                       	Daily exposure (ag/day)	
                                     Assuming Maximum Adult Assuming Reference
                                       Intake^ and Maximum    Intakeb and Media
Trihalomethane  Concentration (aig/1)  Concentration in Water Concentration in Wa
                    Median  Maximum                                      ~

Chloroform           0-059   0.540             1.2                   o 1

Bromoform            0.004   0.280             0.6                   0.007

Dibromochloromethane 0.004   0.290             0.6                   0.007

3romodichloromethane 0.014   0.180             0.4                   Q.02
a2.1S liter  per  day

 1.65 liter  per  day
  Source:  Perwak,  et al.  An exposure and risk assessment for  trihalo-
          methanes.  Final Draft Report.  Contract EPA 68-01-5949.
          Washington, DC:  Office of Water Regulations and Standards,
          U.S. Environmental Protection Agency; 1980.
                                   7-24

-------
 procedures; hence there is considerable uncertainty attached to the values
 shown and the calculated exposures.  In such a case, it may be desirable
 to be conservative, that is, to overestimate, rather than underestimate
 typical exposure levels.  In this example the population sizes were esti-
 mated by extrapolating the percentage of water supplies in which the
 compound was detected in the sample to the percentage of the total U.S.
 population exposed.   This extrapolation does not incorporate many compli-
 cating factors,  and the distribution in size of water supplies is assumed
 to be the same in the sample as in the U.S.  Though this assumption may
 be valid for surface water,  it is probably invalid for groundwater supplies
 in which sampling has been very limited.

      Table 7-9 shows human exposures to trihalomethanes via drinking water,
 as estimated fay  use  of maximum and median observed concentrations and con-
 sumption levels  (Perwakjet al.  1980b).   This table indicates (as  does
 Table 7-8)  that  a wide range of exposures can occur.   In general  it is not
 possible to  determine  the population distribution of exposure  levels.   At
 best, usually a  median,  mean,  or "typical" and a maximum exposure  can be
 estimated.

      Dermal  Absorption

      Dermal  absorption of  a  pollutant  from ambient  or  treated water and/or
 directly from the use  of  the chemical  or  product  contaminated by  the  chem-
 ical  should  be examined  in an  exposure  assessment.   The  process of  esti-
 mating^ the '^average  daily  intake"  of a  pollutant  by the  dermal route  is
 slightly different than for  other  exposure  routes;  the  concentration of
 pollutant  in the  water or  solutions, the nature of  the  chemical contacted.
 the time  of  contact, and the area, location  and integrity of the skin
 exposed  can  all affect the uptake.

      The  first step  is to examine  the types  of human activities in which
 direct contact exposure to the  pollutant can occur.  In  addition to work-
 place exposures or contact with pollutants during manufacture, the exposure
 potential of use  situations must be examined carefully,  e.g., exposure
 resulting from:  mixing or application of pesticide formulations; pollutant
 containment  in paint,  glue, stain, or similar materials; use of cosmetics,
 gasoline or  cleaning solvents; polymers, films or fibers in apparel or
 other products, etc.   Laboratory data on the rate of absorption through
 the skin may be available for a few chemicals.  In  the absence of such
 data,  estimates might be made through use of octanol/water (or other) par-
 tition coefficients,  although these procedures are unvalidated.   Thus,'in
many  cases, the exposure analysis will be limited to establishing the
nature of the exposed population, its size, other characteristics  affecting
 the exposure (duration and frequency of exposure,  extent and area of the
body exposed) and perhaps an extrapolation of rate based upon the rate of
absorption of similar chemicals.  Data seem to be available concerning
chemicals used in pesticides  and cosmetics; because of the variety of the
chemicals used and the apparent variation in rates of absorption,' these
data may not  be very  useful in general  estimates  of average daily  intake.
                                 7-25

-------
    the second category of exposures that should be examined is the ex-
posure of the general population and specific subpopulations who are in
contact with ambient or treated water which may contain the pollutant
as a contaminant.  In this case, three steps are required:

    (1)  defining the numbers of persons exposed and the characteristics
         of the exposure;

    (2)  estimating the concentrations of pollutants in water to which
         persons are exposed; and

    (3)  estimating the rate of transfer from the water to the person.

A considerable body of literature exists on the number of persons exposed
to various activities which involve water—swimming, boating, bathing,
fishing, dishwashing, etc.  Data on seventeen exposure activities in
personal, recreational and household categories have been identified
and summarized by U.S. EPA (1979) including estimates of the populations
exposed, extent, frequency or duration of exposure.  Estimates of the
concentrations of pollutant in the water used in these activities can
come from monitoring data or frora estimates generated in the materials
balance and environmental fate arid pathways analyses.

    Estimating the rate of absorption through the skin is more difficult.
An analysis of this process (U.S. EPA 1979) indicates that the diffusion
rate of the pollutant through the stratum corneum layer of the skin may
be the controlling factor; this is dependent upon the permeability co-
efficient of the pollutant and the partition coefficient of the pollu-
tant between the human skin and the water.   Some data exist upon which
to base estimates; laboratory investigations of the diffusion rate of
pollutants through skin are in progress.  Through combination of analysis
of activities involving water, concentrations of pollutants in water, and
rate of absorption through the skin, order of magnitude estimates of the
actual exposure by dermal contact—in terms of an average daily intake
for various activities or subpopulations—can be made.

    Table 7-10 gives some examples of the estimated dermal exposure to
pollutants based upon absorption through skin.  The estimates for penta-
chlorophenol (PGP) were based on a permeability constant for phenol
(Scow e_t_ al. 1930).  For the halomethanes,  a permeability constant for
chloroform was used (Perwak  e_t al. 1980b) .  In most cases, dermal ex-
posure levels are small compared with those of other routes.  However,
they can be large, as indicated by the home-use of PCP as a preservative.

    Other Exposure Routes

    Some other specific exposure routes should be considered for selected
pollutants.  A major category is the use of medical products.  For example,
food supplements for humans can greatly increase exposure (i.e., zinc,
copper, other trace nutrients).  Intravenous solutions and other products—
plasma, blood, dextrose or saline solutions—can be a means of entrv of
                                 7-26

-------
            TABLE 7-10.   EXAMPLES  OF ESTIMATED  EXPOSURES  TO POLLU-
                         TANTS  BY  ABSORPTION THROUGH THE  SKIN
                                                   ESTIMATED
                                                   EXPOSURE
 POLLUTANT  EXPOSURE                                 (mg/dav)

   Psntachlorophenol:

      Persons bathing and dishwashing               0.003  - 0.03
      with contaminated water

      Home use of PGP as preservative               ]_JQ

      Handling of treated wood                      0.5
   Trihalomethanes:
      Children swimming 1 hr/day in
      freshwater pool containing
      ^160 ug/£ chloroform                         0.2 (chloroform)

      Children swimming 1 hr/day in
      saltwater pool containing
      n-6Q ug/i bromoform                           0.7 (bromoform)
Sources:   Scow, K.  et_ al.   An exposure and risk assessment for penta-
          chlorophenol.   Final Draft Report.   Contract EPA 68-01-3857.
          Washington,  DC:   Office of Water Regulations and Standards,
          U.S.  Environmental Protection Agency;  1980.

          Perwak,  et al.   An exposure and risk assessment for trichloro-
          methanes.   Final Draft  Report.   Contract  EPA 68-01-3857.
          Washington,  DC:   Office of Water Regulations and Standards,
          U.S.  Environmental Protection Agency;  1980.
                                   7-27

-------
 a pollutant  to  humans  both  from contamination  of  the  fluid  or from the
 packaging  material  or  tubing.   Similarly, dental  materials  and surgical
 implants can be a source  of exposure.  The contributions  of these  sources
 to  total exposure levels  are highly variable,  but can be  very significant
 for some pollutants and subpopulations.

 7.3.1.4  Summarizing Exposure

     As a result of  exposure analysis, exposure to a pollutant by various
 routes can be summarized  for the general population and for specific
 sufapopulation groups.  In this  way, the activities that are most responsible
 for human  exposure  can be identified, ranges of exposure  levels can be
 developed  and used  to  help  estimate the risk associated with exposure,
 and pathways  of exposure  can be examined in order to determine  the
 potential  effects of changes in control regulations.

      The results of an exposure analysis for lead (Perwak,  ejC  al.  1982b) are
 shown in Figures 7-1 through 7-3 and Tables 7-11  and 7-12.   As shown in
 Figure 7-1,  the exposure  routes for humans are numerous and  complex.
 The ingestion of paint chips is commonly thought  to be the most pre-
 valent lead  exposure problem in the U.S. today, and this  is  borne out
 by  the high  exposure levels shown in Figure 7-3.  and Table  7-11.  Intake
 of  lead in food is the primary  pathway for adults not employed in lead-
 related industries and among children without pica (Figure  7-2).  Inhala-
 tion  exposures,  shown  in Table  7-11, are heavily  influenced by proximity
 to  industrial sources.

    Data were available to permit estimation of the rates of absorption
 of  lead, and  exposure  levels have been converted  into absorbed doses
 in  Figures 7-2  and 7-11.   The relative contributions of exposure routes
 as  absorbed doses to the exposure scenarios for adults and children with
 pica  are displayed in  these figures.

     Exposure may also  be  measured  by  other parameters,  such as levels  in
 blood or tissue.  In some cases, this  information can be combined with
 actual effects  information from epidemiological studies to achieve an
 estimate of risk.  This was the case for lead,  and this information
 (shown in Table 7-12)  in combination with the exposure estimates can
 give a good basis for the identification of sources  of'risk.

 7.3.2  Effects Analysis

 7.3.2.1  General Approach

    In developing an approach to address  the  effects  of toxic substances
 in the environment on humans, a number of issues  deserve attention.
First, one  must  determine  what  effects should be  considered  in the  analysis.
                                 7-28

-------
Source:
       FIGURE 7-1  EXAMPLE OF GRAPHIC SUMMARY OF ROUTES
                   OF HUMAN EXPOSURE TO LEAD

Perwak, J. et_ al.  An exposure and risk assessment for lead
Final Draft Report.  Contract EPA 68-01-3857.  Washington, DC:
Monitoring and Data Support Division. Office of Water Regulations,
U.S. Environmental Protection Asencv: 1982.

-------
                  Air - 1%
      Rural Areas —
                                     .
                                   Dnnk.ng
                                   Water - 1 %
                                                                 (lead solder in
                                                                 cans - 25%)
                                                       Urban Areas — 50 jug/day
                                   (lead solder in
                                   cans-31%)
 Note:
               Smelters, Lead Works, etc. - 160 .ug/day


Concentrations < 10 jug/2 in drinking water were assumed for these estimates, and no con-
sumption of wine or moonshine containing lead. In addition, these situations did not include
exposure from smoking.

FIGURE 7-2  EXAMPLE OF  GRAPHIC SUMMARY OF  ESTIMATED EXPOSURES
             TO  LEAD FOR THE GENERAL ADULT  POPULATION
Source:   Perwak,  J.  et al.   An exposure and  risk assessment  for lead.   Final
          Draft  Report"]   Contract.  EPA 68-01-3857.  Washington, DC:
          Monitoring and  Data Support Division, Office of Water Regulations,
          U.S. Environmental Protection Agency; 1982.
                                       7-30

-------
                    Drinking Water - 1%
                                                          Drinking Water and
                                                  Food (4%)  /Air - 1%
                       Paint and
                       Paint
                       Contaminated
                       Dirt
                       (90%)
         Rural - 560 Mg/day
                            Drinking Water
                            and Air - 1%
                      Smelters. Lead Works, etc. - 1300 Kg/day
FIGURE  7-3
ource:
        and
                 EXAMPLE OF GRAPHIC  SUMMARY OF ESTIMATED EXPOSURES TO
                 LnAD  FOR A SPECIFIC SU3POPULATION  (CHILDREN WITH  PICA)
          •>  J.  &£ Al.  An  exposure and  risk assessment  for lead.
        .- Report.  Contract  EPA 68-01-3857.   Washington,  DC •
        .toring  and Data Support Division,  Office of Wate- Re
-------
   TABLE  7-11
                  EXAMPLE OF EXPOSURE ESTIMATES OK  LEAD FOR ADU]TS
                  AND CHILDREN INCLUDING ESTIMATED  ABSORBED DOSE
 Iocat ton
 Kural
I'll..1.1
 ;lt Ing Area-.
                 Food
                 Prinking Water
                 InhalacIon
                Drinking Water
                Inhalation
                l-ood
— —

1. it al liK-i

M, Him, hi II,.'
Wine

MOM SupplU...
UNUdiilnad.d
Highly Con t ami i ill 1
Suburban
'""" '•'

T,,tal lilct
M, Hill ,1,1 lll_
Wlnu


Mo:»l Sniip 1 li ;»

(•ontaulnatcU
Highly Coiiianiln.il 0,1
Hi L. in Air

1 ot a 1 t)i » t
W | rif


Asa ijm[>( 1 on



1 ">K/1 . 1 I/day
0.2 oig/1. 1 I/day
0.-' »t;/k. 5 I/day
' 10 uB/l. 2 I/day
• JO ,,g/l. 2 l/dav
- 1000 ,,K/|, . j/djy
See Table 5-lb
See Table 5-lb


1 "IS.M. 1 1/djy
" • * lft^J/1, 1 1 / J .1 y
0.2 iug/1 5 |/ddy

' 10 UK/1. 2 i/day
i« .'g/1. 2 1/Jay
1000 llt!/l. 2 I/day
See Table 5-lb


' ""«/». 1 I/day
°-2 «K/I . 1 I/day
".2 »B/1, 'j I/day
lii; .ike
(iig/duv)

100-200
10OO
200
1000
<20
• 1OII
> 2000
l.S-IS
0.4
-

100-200
1000
200
1000

< 20
• 10O
' 2000
li-62
-

1000
200
IO(/U
Ah^oibcd
TT.'gTjL

. .
100
11)0
v.

• .'Oil

•1. 1
1-5

lU-.'U
10 >

IUU

,
-
JOO
i-JI
1 -b

loo

fc 0
IOIJ
                                                                                                                  Do:,

-------
        Population
        CMldn-n
 I
Lo
U)
                                     TABLE 7-11.   EXAMPLE  OF  EXPOSURE  ESTIMATES  OF  LEAD FOR ADULTS  AND
                                                      CHILDREN INCLUDING ESTIMATED ABSORBED DOSE  (Continued)
                           Location
                          Rural
                                             I'l i III 1.1,; W.I. I
                                             Inhalation
                                             Food
                                             Drinking Ua
ar ton
                                                                             Source-
                                                                    MCI;, I  Sup
                                                                    (..mi .nulli
                                                                    •Uglily C
                                                                   Aablunt Air
                                                                   Cigarettes
                                                                   Total
Contanlnaled
Illglily Con tau Ina l

Aoibtent  Air
                                                          '"' JL'i'J'1 '' '

                                                     •10 ,,„/!. I l/.,jy
                                                     ' 'M UK/I . - i/Jjy
                                                     '1000 Mg/l. *  |/.|.,y
                                                     10 us/".1.  -'0  »,J/djy
                                                                                                       10  Hi/1.  I  l/d.iv
                                                                                                       50  ug/l.  1  i/j.,,,
                                                    See TabJe 5-l
                                                                                                                                    I II C.I k 1-
                                                                  ' Idl)
                                                                  2OMO
    100

   <10
   <50
 •' moo

0. 11,-l.t,
                      > IU
                     > 20(1
                                                                                                        60
                                                                                                     0.1-1
                         Urban
                                                                   lead  Paint
                                                                   I'alnt or Othe
                                                                   (uiil amlnaliij
                                                                  Totjl
                                   IX  Uad.  1 mg chip
                                   1000 ng/,- K-a.l  |n
                                   10 UK/Bum h ing, 10
                                  0 l.g/1. 1 1/Uay
                                                                                                     <50 l.g/1. 1 1/djy
                                                                                                     > 1000  Mg/1. 1  |/Jjy
                                                                                                                                  > 1OUO
                                  II lead.  1  ag chip             1000
                                  1000 jjg/g JeaJ in  din,          JUQ
                                  10 BK/uouthlng.  IU numtliln,;;./
                                  day
                                                   10.000 ,lt/B |e.,d !„ dusi
                                                   10 UK diiit /imuillilllK, 10
                                                   nout h Ingtt/dav
                                                                                                                                   |O00
                                                                                     <5
                                                                                    <25
                                                                                   > iOO
                                                                                                                                                        so
                                                                                                                                                       soo

-------
                                 TABLE  7-J1.   EXAMPLE OF  EXPOSURE ESTIMATES OF LEAD FOR ADULTS  AND
                                                 CHILDREN  INCLUDING  ESTIMATED ABSORBED DOSE  (Continued)
                     i .111
                      li hi.1.  Ale. i.,
                                          Knute
                                     Orluk I Hi; Water
                                         l.il Ion
                                                                                                                            Intake
                                     I' lea
 tin.11 III el


Host SuiM'lli-'a
root.milnacc'il

Highly Cunt Jlaln.il


Ami. li-llt  All


Lead Pdlnt
Dirt

AautimcJ tu he half ut
adult
• 10 PB/l. 1 I /day
'50 „,./), 1 |/JJV
• I'»00 i,B/|. 1 |/.|.JV
(lift/day)
500
< 10
-50
> 1000
                                                                                                 t'B/*1.  i  w'/d.lv
                                                                                              IT  U-.iJ,  I i,.,
                                                                                              HI »n/u:.Hilliiii[;.  |(| momli
                                                                                              J.iy
                                                                                              10.000 i,j../B  U..,.  ,,, j,,.,t
                                                                                              Hi mi; duat /ii..iul.inK. lo
                                                                                              >i.<.il I. liH'a,',! i,1
                                                                                                                             40
                                                                                                                           1 1 II ID
                                                                 too
                                                                1000
                                                                                                                                             (lig/djy)
                                                                                                                                               < i
                                                                                                                                               U
                                                                                                                                              idl)
 SO
500
 J0% absorption of  ingested lead is assumed for ad.Uia and SOX for children.  U-oosltion
^Inhaled  ledd  is assumed  to he JOJI and 100% if deposited lead is assumed to be -bsorLcd?
 Table 5-1 in  source cited  below.

Sour,..!:  Herwak. J. ej, .U.   An exposure and risk  assessment  foi  leao.   Final Draft Report
         Contract EPA 68-OJ-M49.   Washington.  DC:  Monitoring and Data Support WvUion  '
         OfUce of Water  Regulations  and Standards. U.S.  Fn»ir.-.n.	,1  „,„,'_.,_.. .
         »009                                      *       —' *" —•*•*••*-•• •••••  • *»>*-t.»_«.iuii /njency,

-------
        TABLE  7-12.   EXAMPLE  OF LEAD  LEVELS  IN BLOOD IN
                      SUPPORT  OF EXPOSURE ESTIMATES
LOCATION
Adults

Rural/Urban
Urban
Rural
Within 3.7 meters
of Highway

Living Near a Smelter

Children

Urban (primarily)
Within 30 meters
of Highway

Near Smelter—Kellogg,
ID—1974 (immediate
vicinity)
1975

1979
El Paso, TX
BLOOD LEVEL
(ug/100 ml)
 9-24
 Most
 REFERENCE*
 Ball  et  al.  (1979)
                                    16
18—mean (adjusted for age   Tapper and Levin
and smoking)
Less than 5% >30

16—mean (adjusted for age
and smoking)
Less than 0.5% >30

23—mean


16% >40
                                                          (1972)
Daines et al.  (1972)


Landrigan et al.  (1975)
40,000 children detected
annually >30

•\ 20 yearly geometric mean   Billick et al.  (1980)
50% >40


99% >40

60% >60

Somewhat reduced'

Almost all >60a,
and most >40

70% >40
14%
Caprio et_ al.  (1974)


Walter et al.  (1980)


Anonymous (1979)




Landrigan et al. (1975)
 Reduction as a result of reduced atmospheric emissions as well as increased
 sanitary procedures for the workers who were apparently exposing their
 children to lead through their clothing.

*See source indicated .below for references.

Source:  Perwak, et al.   An exposure and risk assessment for lead.  Final
         draft report.  Contract EPA 68-01-3857.  Washington, DC:  Monitor-
         ing and Data Support Division, Office of Water Regulations, U.S.
         Environmental Protection Agency; 1982.
                                    7-35

-------
     Second, the spectrum and quality of health effects data available
for use in assessing risk to humans should be examined.  For chemicals
that have long been recognized as toxicants, data may be available from
epidemiologic studies or from reports of effects on humans, as well as
data for laboratory animals; for other chemicals, especially newly
developed ones, only laboratory animal or in vitro data may be available,
if any at all.  As a result, one must be prepared to adapt the scope of
the analysis in accordance with the available data.

     Third, one must consider the format of the effects analysis.
Ideally, quantitative relationships based upon human data would be
developed between the exposure (expressed in terms of specific dose,
average daily intake, etc.) and the response of humans (death, morbidity,
changed reproductitive capacity, etc.).   Generally,  sufficient information
will not be available and, by necessity, data for Laboratory animals will  be
extrapolated to man.  Frequently there will be insufficient animal data
to develop dose/response  relationships and risk will have to be assessed
in terms of no observed effect: levels and appropriate safety factors.
In cases in which no specific data associated with the chemical are
available, the only option remaining will be qualitative statements
based on structure/activity relationships or similarity with other chem-
icals .

     Assessment of potential health hazards associated with exposure
to a particular chemical typically begins with a literature search.
There are many computerized and manual data bases for health effects
and toxicologic data (e.g., CANCERLINE,  TOXLINE, MEDLINE, ENVIROLINE,
etc.) that can be used to obta.in citations concerning human safety as-
pects of the chemical in question (see Chapter 10  for a listing).   The
number and scope of citations  in these data  bases  are expanded  regularly.
By careful selection of key words and  structuring  t:he search  to include
the possible effects of the pollutant, a substantial  amount of  data can
be obtained.

     When the literature has been obtained,  all aporopriate and reliable
human and animal data should be evaluated.  As an aid to the organiza-
tion and analysis of the information,  a matrix of the types of data that
should be analyzed is presented in Table 7-13.  As indicated earlier,
direct human data are more desirable,  but generally not available.
Ideally, if one could fill in the human data columns of the matrix, then
data for the other columns would not necessarily have to be considered.
Not all types of health effects need to be thoroughly studied,  in that
the data needs will be unique for each chemical.  However,  each area
should be examined briefly to determine if it is relevant to the chemical
in question, and if its inclusion in the risk assessment would be useful.

     Once all available information has  been thoroughly evaluated,
judgments should be made regarding the relevance of  the mode  of exposure
utilized in animal studies to that associated wich human exposure.
Interaction of agents that may result  in synergiscic or antagonistic
effects should also be indicated, if known.   On the  basis of  the kinds
                                  -36

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         TABLE  7-]3.  MATRIX FOR INITIALLY ORGANIZING ANALYSTS  OF HUMAN HEALTH EFFECTS INFORMATION


                                 Data on Humans	Mammalian   In Vitro    Inference/Extrapolation from
Health Effects  Information   Epidemiologies]   Accident.    Data     '~"Da_ta~~     Other Related Chemicals

Metabolism, absorption,
accumulation, distribution,
excretion  (pharmacokinetlcs
and mechanism of action)

Acute

Subchronic

Chronic

  Ca r c ino gen t c 1 ty
  MuCageiiicity
  Teratogenicl ty

Fetotoxicity

Functional Disorders and
Effects

  CNS
  Reproductive
  Hepatic
  Renal
  Cardiac
  Gas trointes tinal
  Uespi ratory
  Di gestive
  Circulatory, etc.

-------
of responses induced by the chemical,  an assessment can be made of the
acute and long-term adverse effects that might result from exposure to
the chemical, in a form usable for risk analysis.   The output of the
effects analysis should include:

   (1)  The type and nature of the effects of the pollutant expected in
        humans;

   (2)  The levels of exposure (dose,  intake, etc.) that produce these
        effects in humans and/or experimental animals;

   (3)  The quantitative relationships, if any, that have been docu-
        mented between effect and exposure in humans or experimental
        animals;

   (4)  The variation in effects and exposure/effects relationships for
        different human subpopulations  (age, sex, diet, etc.).

   (5)  The  levels  of exposure at which no effects are observed; and

   (6)  The  level of uncertainty in the available data.

      That  every chemical will induce negative health effects  if adminis-
 istered  in sufficient quantity  is  axiomatic  in  toxicology.  The challenge
 is always  to  establish what exposure levels  are probably non-threatening
 and  what exposure levels are associated with certain risk.  Thus,
 toxicology cannot avoid being a quantitative discipline.

      Human biology, however,  is very difficult  to  quantitate.  Thus,
 quantitative predictions must be developed  for  a highly heterogeneous,
 poorly reproducible system.   As a  result, reported values  are generally
 thought  of as representing some point  (hopefully,  the  midpoint)  of a
 fairly broad range  of  effects rather  than an exact number  to  be_taken
 at face  value.  Any quantitative  conclusions regarding health risks
 must be  reached with care  and with recognition  of  reliability and/
 or limitations of the  data upon which  they  are  based.

      In the sections below,  the types  of  data that are desired for human
 effects analysis  are briefly presented, along with an approach or hier-
 archy for examining and analyzing these data.   Examples  of typical data
 summaries from actual risk/exposure assessments are  presented in the
 discussion.  [In Chapter 9.0, possible methods for extrapolating animal
 data to humans (quantitative risk assessment)  will be discussed.]

 7.3.2.2  Details of Approaches  and Examples

      Absorption,  Metabolism, Bioaccumulation and Excretion

      In studying the effects of a pollutant on humans, it is important
 to  know the  routes by which the pollutant can enter the body; the degree
 of  absorption, if  any; the extent of metabolism; whether the pollutant
                                  7-38

-------
  is accumulated and in what tissues;  and how it is excreted.   These
  factors are imporatnt for several reasons:

       (1)   They form the linkage between exposure of humans to concentra-
            tions of pollutant  in the  environment and the possible effects.

       (2)   They establish the  relative  significance of  the  various
            routes-

       (3)   They may indicate target organ systems-

       (4)   They can aid  in the  interpretation  of data on concentrations
            of  the pollutant in  human  and animal  tissues  (monitoring data).

       (5)   They may provide a rational  basis for estimating the  effects
            of  the pollutant on  humans based upon animal  or  in  vitro
            studies-

       (6)   They may  suggest other  related  chemicals  (metabolites or pre-
            cursors  of  the  pollutant)  that  need to be  examined.

      Recommending a generalized approach to seeking and  evaluating these
 types  of data  is difficult; nevertheless one would  generally start with
 human  data  if  available  and then proceed to experimental animal  data.
 For example, for established chemicals,  pesticides,  and  most metals,
 one can  anticipate  that  epidemiologic studies, as well as animal  data,
 will be  available.   Important considerations needing  investigation
 include:  degree of absorption;  rate  of clearance from blood or  plasma;
 principal routes of  elimination;  sites  and amounts  of residues or
 accumulations  in body  tissues;  the half-life in  the body for the pollu-
 tant and/or its  metabolites.

     For example, if biliary excretion  was found to be a major route
 of  elimination,  species  differences in  the rate  of biliary  excretion
 of  the compound  into the bile might result in specias variation in  the
 biologic half-life of  the  compound and  its toxicity.  Another example
 of  the usefulness of these  data is the  use of tissue  distribution
 patterns in defining populations at risk.  Toxicants  are often con-
 centrated in a  specific  tissue;  some  may be concentrated at their site
of  toxic action, such as carbon monoxide, which has a high affinity for
hemoglobin.   Other chemicals are sequestered harmlessly at storage
sites, but may be released at coxic levels on reniobilization of the store,
e.g., chlordane stored in body fat, can be remobilized under weight loss
conditions;  lead stored in bone can be remobilized with increased calcium
demand, such as during pregnancy and/or lactation.

     Another reason for  reviewing metabolic and  pharraacokinetic data is
 that some substances in  the environment  are also essential  elements or
nutrients in many specias,  e.g., copper and zinc.  Understanding the
pathways and uses of the element in the body can help co establish whs-he-
                                   7-39

-------
the amounts obtained from environmental sources are excessive  for normal
body function and whether large or small increments can lead to  toxicity.
In the case of copper, for example, one finds that absorption  of ingested
copper is very incomplete (Venugopal and Luckey 1978).  Furthermore,
ionic copper has a strong emetic action.  As a result, ingestion of
copper and its salts in small quantities does not usually present a high
risk.  Inhalation of copper dusts, fumes or copper-containing  products
may present a more serious risk (Perwak, et al. 1980a).

     Other examples could easily be drawn from the literature, but these
should suffice to indicate the importance of metabolism, accumulation,
pharmacokinetics, and mechanism of action data in effects analysis.

     Acute Effects

     Although cases of acute human effects resultings from exposure to
environmental pollutants are not very prevalent, it is important to
examine acute human toxicity dz.ta for several reasons:

     (1)  acute accidental or occupational exposure to high concentra-
          tions of pollutants may be the only human data available;

     (2)  acute effects may identify specific organ systems at risk to
          chronic exposure;  and

     (3)  the comparison of acute human effects with animal data combined
          with metabolism and ether data,  can support the use of chronic
          animal data for extrapolation to humans.

     The majority of acute human toxicity data that is most often avail-
able in the medical literature, "poison centers," and/or NEIS3, results
from suicidal or accidental exposure,  often in children.   Standard tests
on industrial safety and hygiene may also contain acute toxicity values
for inhalation, ingestion, and dermal absorption.  Although large bodies
of data from humans are often not available,  the types of acute toxicity,
symptoms, and effects,  and in some cases,  minimal lethal values for man
are generally available.   The minimum lethal  dose,  however, only indicates
chat a single death due to the chemical has been recorded at that dose
which may be the results of a high dose accident or suicide attempt.   In
fact, the minimum lethal dose may be equivalent to  an 105 (the dose found
to be lethal to 57, of the exposed population) ;  or it may be many times
higher than an LDgg (the dose found to be lethal to 90% of the exposed
population).   Thus,  quantitative conclusions  on human risk must be reached
with care, according to the limitations of the data,,

     Data may also be available concerning the acute toxic effects of a
chemical in laboratory animals, particularly  rodents.   Acute toxicity
studies provide information on the relative effects of different expo-
sure routes (inhalation,  ingestion, skin contact),  provide a measure of
comparison among many substances whose mechanism and sites of action may
                                  7-40

-------
 be markedly different,  and are roughly indicative of the effects  of
 chronic exposure to small amounts  of the chemical.   Acute toxicity tests
 are also frequently conducted  to determine local effects of  chemicals
 when applied directly to the skin  or eye.   Thus, acute  toxicity studies
 place the overall acute toxicity of different  pollutants in  perspective.
 In the development of new chemicals,  for example,  these acute  tests are
 often used as an initial screen to aid in the  determination  of whether
 or not to continue to develop  a chemical.   Such  tests are also required
 by regulatory agencies  for pesticides,  drugs,  food  additives,  etc.

     There are not generally accepted  standard  data  to search for,  or
 special means of data presentation.   A clear understanding of  the  impli-
 cations  of the data  is  the  important  concern.  For  example,  very low
 exposure levels  of cyanide are very acutely toxic,  but  are rapidly
 cleared from the body (Williams 1959),  while lead may present  no acute
 toxic response at low levels,  but  its  accumulation  in bone can result
 in grave consequences to man (Mahaffey 1977).

      Subchronic  Effects

      Subchronic  testing involves the  administration of  the test chemical
 on multiple occasions.   Experiments are generally conducted  for 90  days
 with rats or mice,  for  6 months to  1  year with dogs.  Subchronic studies
 are typically conducted at  higher  exposure  concentrations  than chronic
 studies.   Pathologic  changes are thus more  clearcut because  they occur
 more quickly with the higher doses  and  are  not obscured  by other chronic
 changes  such as  aging.   For  example,  focal  myocarditis  is'a  common
 spontaneous  type of lesion  found in high frequency  in aging  populations
 of  rats  (Simms 1967).   A marked increase in the  incidence  of this lesion
 after 90  days' exposure would be noteworthy, but might be  attributed to
 aging or  a small population remaining at termination of  a  chronic study.

      Carcinogenicity

      Cancer  is characterized by an uncontrolled growth of  abnormal cells:
 a carcinogen  is  defined  as any  toxic substance which has been demonstrated
 to  cause  tumors  in mammalian species by induction of a tumor type not
 usually observed, or by  induction of an increased incidence of a tumor
 type  normally seen, or  by its appearance at a time earlier than would
 be  otherwise  expected (National Cancer Institute 1976).

     As is  the case with other effects, examination of carcinogenic risk
 begins by consideration of human epidemiologic data, if available.
 Figure 7-4 presents in  flow chart  form a procedure for  evaluating  data
 on carcinogenicity.  Ideally, one would follow the yes  pathways to
develop the most reliable estimates of the carcinogenic  effects of the
 pollutant.  Thus the chart is organized so that the items in  the bottom
 row appear from left to right in order of descending desirability  and
reliability.  If data are limited  to in vitro data,  data on related
compounds, or structure-activity relationships  (SAR), the risk  of  carcino-
genicity can probably not be assessed reliably.
                                 7-41

-------
-J
I
-p-
NJ
                                     FIGURE 7-4     FLOW CHART FOR CARCINOGEN RISK EVALUATION

-------
      The route shown on the left-hand side of Figure 7-4, based entirely
 upon human  data,  is  the ideal path  in evaluating  carcinogenic  risks,  but
 will in  reality very seldom be  used because adequate  data  are  lacking.
 Epidemiologic  data,  even if available, most often do  not represent
 causal relationships, only correlations or associations, and must thus
 be  augmented by other types of  data.  Reports of  occupational  exposure
 give a somewhat more direct indication of causality,  but the dose-response
 relationships  may be difficult  to define.  Thus,  in most cases, human
 data alone  will not  provide a suitable risk estimate, although coupled
with experimental animal data,  they may permit a more rigorous analysis.

      If experimental animal data are available,  there are four possible
 routes to assessing  risks depending on, first, the number of species
 tested and, second,  whether or  not  dose-response  relationships are known.
 In  following any  of  these paths, careful attention must be paid to the
 quality of  the data, the incidence  of spontaneous  tumors in the control
 population, consistency if more than one study is available, and
 statistical validity.  If the exposure route and  experimental  regimen
 employed  (e.g., intra-muscular  injection) do not  agree with  the most
 likely mode(s) of human exposure, the data must be interpreted
 cautiously.    Consideration should be given, to data on metabolism of
 the compound by the  animal species  tested, as compared with metabolism
 in  humans if this information is known.

      If only  in  vitro data are available, only qualitative estimates
 may be possible because of uncertainties regarding the association
between in  vitro  results and human  or animal effects; the availability
 of  associated  pharmacokinetic data, however, may allow an approach to a
 rough quantitative estimate.   Even  less reliability will be possible  if
no  experimental data are available  and only SARs  can be established
between the compound and related compounds for which data are
 available.

     In following the path indicated in Figure 7-4, information from  the
National Cancer Institute's carcinogenicity programs should be examined,
as well as data from the medical literature.   Discussions with qualified
toxicologists/oncologists should supplement a critical analysis of the
literature for chemicals for which the data are equivocal or conflicting.
For example, animal studies weakly support an association between exposure
to benzene and carcinogenicity  (Snyder &t_ al.  1980), but the evidence that
benzene is a leukomogen for man is convincing (Askoy 1977;  Infante at. al.
1977a,b;  Ott jet aJL.   1978).   Benzene may in fact play a co-leukomogenTc
role,  which would  explain the failure to induce leukemia in several
benzene-exposed animal species.
                                  7-43

-------
      Mutagenicity

      A mutation can be defined as any heritable change in the genetic
 material (DNA)  of a cell or organism.  Among the sequelae of a°mutation
 are cell death, altered structure and/or function,  and no overt immediate
 effect, should  the mutation be unexpressed fay virtue of its recessive
 nature.  The types of changes  that occur in the genetic apparatus of a
 cell can range  from modifications in the individual base pairs, result-
 ing in point mutations in a single gene,  through major chromosomal
 structural changes that may involve entire sets of  genes,  to disruption
 of entire sets  of chromosomes.   Some examples of these kinds of occurrences
 in humans are sickle cell anemia (an example of point  mutation) and
 Trisomy 21 (Down's syndrome, an example of a major  chromosomal disorder).

      Some relatively rapid and technically accessible  bioassays for
 mutagenicity are  being used as  predictive  tools to  identify not only
 agents with possible mutagenic  activity, but also those that may induce
 cancer or cause a teratogenic  response.  A large amount of  experimental
 evidence indicates that many agents  that are carcinogens also can damage
 DNA,  and the correlation between activity  of chemicals  in the mutation
 screens and activity as carcinogens  is  high  [e.g.,  the  Ames test has been
 found to be 80  to 90% accurate  in detecting  carcinogens as  mutagens
 (McCann et_ al.  1975)].   This and similar tests  are  widely used  as an
 initial testing mode to identify potential genotoxic agents,  although
 correlations between potency and response are often not good.   Thus,
 testing for mutagenicity  has wider  implications  than merely determining
 the  potential for mutagenic ris
-------
 I
f>
Ol
                    Are there
                      human
                      data?
                                                         Are there
                                                       experimental
                                                           data?
                                                                                                                     Structure
                                                                                                                      activity
                                                                                                                    relationships
                                                                            Specific
                                                                            locus or
                                                                            heritable
                                                                          translocaiion
Are there
  direct
  data?
                                Are there
                                 indirect
                                  data?
                                                                          Evaluate assays
                                                                                  Evaluate assays
1. Epidemiology
2. Fetal wastage
1. Cytogenetics
2. Urinary mutagens
3. Sperm morphology
4. Testicular atrophy
                                                                                       Extrapolation to humans
                                                                  Risk Estimates
                                                                                                                                 Only very
                                                                                                                                 qualitative
                                                                                                                                 risk
                                                                                                                                 assessment
                                                                                                                                 statements
                                                                                                                                 possible
                                           FIGURE 7-5    FLOW CHART FOR MUTAGEIMICITY RISK EVALUATION

-------
and time required for the specific locus assay, there is not much likeli-
hood that this test will be used for materials except those that may have
a large medical and/or social importance.  Thus, the heritable trans-
location assay appears to be the only readily available experimental tool
at this time for a direct measurement of transmissable genetic damage.
Its major disadvantage is that it measures only male-originated changes,
and it too is a relatively large and expensive bioassay.


     The remaining battery of genetic tests, though useful, are only
indicative and the results must be evaluated with considerable care for
appropriate use in the risk analysis process.  A number of criteria should
be examined in order to establish the usefulness of the experimental
data obtained from bioassays:

     (1)  heritable versus non-heritable changes,

     (2)  phylogenetic hierarchy,

     (3)  genetic endpoint,

     (4)  sensitivity of assay system, and

     (5)  validation of assay data and assay system.

These criteria are interdependent and complex,, so that a simple treat-
ment of these variables is not likely to be possible.

     For example, a marked increase in chromosomal aberrations was noted
(see Table 7-14) in mouse spermatogonia following gavage administration of
doses of aqueous phenol solution far below levels associated with other
effects and at environmental exposure levels that a large fraction of the
human population may encounter (Bulsiewicz 1977).  In addition, an apparent
trend toward increased aberrations within a single treatment group in each
of five successive generations was evident.  In that (1) most mammalian
species, including man, handle phenol biologically in a similar manner,
(2) the treatment route of this study is the same to which man will
likely be exposed, and (3) in vivo cytogenetic analyses in mammals are
considered more relevant than similar tests in vitro or genetic tests
with lower organisms for predicting a mutagenic hazard for man, Bulsiewicz's
results were cause for concern.  Unknown factors, however, such as tissue
and species made any discussion of the genetic implications of the re-
ported chromosomal aberrations for man more speculative than factual.

     The means by which genetic assay data should be used in a risk assess-
ment has been considered by a number of prominent investigators in the field
(Freese 1973, Crow 1973, Bridges 1974, and Report of a Committee of the Euro-
pean Environmental Mutagen Society 1978).  They generally agree that risk
analyses and subsequent action based on experimental tests other than the spe-
cific locus and heritable translocation assays would not be easily supportable
                                  7-46

-------
         7-14.   EXAMPLE OF PRESENTATION OF MUTACENICITY DATA—INCIDENCE OF
                CHROMOSOMAL ABERRATIONS IN SPERMATOCONIA OF PHENOL-TREATED MICE
Dosage
Generation (ug/kjjy
P 0
6.4
64
640
' 0
6.4
64
640
K-> o
6. 4
64
640
K3 °
6.4
64
640
F4 0
6.4
64
640
r5 0
6.4
64
640
Level Chromosome
'day) Breaks
0
1.7
5.8
9.2
0
3.3
10.8
12.5
0
9.2
15
19.2
0
5.0
10.8
10*
0
6.7
15.8
20
0
10
17.5
51.3*
Chroma t id
Breaks
0.8
3.3
5
7.5
0
10
15
14.2
1.7
8.3
15.8
17.5
0
5.8
14.2
10*
0.8
8.3
20
25
0
6.7
23
37.5*
Aneuploidy
0
1.7
5
10
2.5
11.7
15
17.5
0
9.2
17.5
19.2
0.8
13.3
22.5
36*
0.8
10
20.8
27.5
1.7
13.3
25.8
37.5*
Polyp loidy
0.8
3.3
10.8
13.3
2.5
1.7
15.8
19.2
0.8
5
14.2
22.5
1.7
8.3
15.8
32*
0.8
6.7
23.3
30.8
0
11.7
21.7
56.3*
A,
Associations
o
0 ft
2.5
1.7
o
3 3
5.8
7.5
o
5 n
7.5
5.8
0 1
3.3
9.2
8.0*
o
10
15.8
.17.5
0 2
6. 7
19.2
25*
Excludes 3 mice killed  in moribund condition.  Preparations made  from  the  testes  of  these mice showed
 absence of primary  and  secondary spermatocy tes . spermat ids, and spermatozoa.
Source:
   Scow,  et al .  An exposure and risk assessment for phenol.  Final Draft Renorr   Pnnrr^
   EPA-68-01-59A9   Washington, DC:  Monitoring and DLa Support DlvSon, Office  of Sater
   Regulations and Standards, U.S. Environmental Protection Agency; 1981.

-------
Moreover, these investigators believe that a positive finding in the
heritable translocation assay should be given considerable weight in a
risk analysis.

     No special data presentation methods need to be considered in muta-
genicity analysis; careful reporting of the interpretations of others
and correlation of one series of tests with another are, however,
important.

     Teratogenicity

     Teratology can be broadly defined as the study of malformations of
the newborn that occur as a result of an adverse effect(s) on the develop-
ing conceptus.  In the past, the term malformation implied gross anatomic
malformations; but in recent times, the term malformation  has been
broadened to include more subtle, functional abnormalities and even
postnatal behavioral and intellectual development.

     A teratogen, the agent ex&rting an adverse effect on the developing
conceptus, exerts its effect in the time interval between conception and
the termination of morphogenetic development in the post-partam animal.
The picture is complicated somewhat in that certain morphogenic events
are terminated at widely varying times in different species.   For instance,
re-opening of the eyelids, opening of the external acoustic meatus,
formation of the vaginal lumen, and descent of the testes occur pre-
natally in man, whereas these events take place postnatally in the mouse,
rat, and rabbit, the species mcst often used in experimental studies.
In addition, other factors such as metabolic differences, excretion rates.
placental variations, age of the dam, and nutritional status  may all in-
fluence the potential teratogenicity of a chemical Ln a particular species.
Moreover, the dose,  route, and time of gestation at which a conceptus is
exposed are critical in defining whether a particular chemical is tera-
togenic in a particular species .

     The assay procedures presently available to test for the teratologic
potential of chemicals are empirical, largely because the detailed biological
mechanisms of teratogenesis are not well understood.   Clearly, under-
standing the mechanisms of teratogenesis would be the most fruitful
approach to predicting the risk of exposure to new chemicals  or even well
established ones.  Unfortunately, the state of the art of understanding
the mechanisms of action of most known teratogens is  quite primitive.
There is evidence to support about 8-10 mechanisms of action:   mutation,
chromosomal aberrations, mitotic interference, altered nucleic acid
integrity or function, lack of precursors and substrates for  bio-synthesis,
altered energy sources, enzyme inhibition and osmolar imbalance and
altered membrane characteristics (Wilson 1977).   All  of the above mech-
anisms are not mutually exclusive,  i.e., both genetic and environmental
factors determine tertatogenic risk.   In addition, nany of these mech-
ansisms are non-specific effects seen only at high doses (e.g.,  enzyme
inhibition,  altered  energy sources)  and extrapolation of these findings
to man is of questionable value.
                                 7-43

-------
      This lack of information on the mechanisms of teratogenesis is high-
 lighted by the findings that show chemicals to which humans are widelv
 exposed such as aspirin, vitamin A and hydrocortisone, to be teratoeenic
 in certain experimental systems.  Although there are no data to eliminate
 these chemicals from consideration as human teratogens, there is also no
 evidence that their consumption by pregnant females or by males prior to
 fertilization at doses normally employed has resulted in malformation in
 their _ progeny.   In contrast, methyl mercury and methotrexate, which have
 been implicated as human teratogens, induce a teratogenic response in a
 wide range of species, including the smaller rodents  usually employed in
 most experimental studies,  i.e., mouse,  rat,  Syrian hamster.

      One means  of approaching a better understanding  of the relationships
 between teratogenic effects of chemicals in humans  and in experimental '
 animals is to examine those instances for which a chemical has  been
 identified as a human teratogen and has  been  tested later in  experimental

 SSdo* 'd   ?°SK  WSl1  kn°Wn "^  °f thiS C^e is  the «« concerning
 oflhe  ±M.      ".especially instructive,  since it illustrates  sLe
 nfd               °  US§ experimental animal data in  a prospective  manner.
 Had
                                                                    ma
                 been tested for teratogenicity according to the usual
 protocols in rats or mice,  there would have been little or no indication
 of any problem   In rabbits and subhuman primates,  however, thalidomide
 was demonstrated to be a potent teratogen.                      ^aomiae
fr0m ?^VhS Pr±maf7 difficulties in extrapolating experimental data
from laboratory animals to man is the high probability of differences
in metabolic fate of chemicals, especially their disposition in Jonadal
or placental tissues.  Moreover, because of the compLx behaviorll

        a
of
                                                           avor
            l™CtiC*S°f humans> to contrast to the controlled regimens
          ^   Timal tSSt P0^'10"3'  there -ay be wide individual
          among humans witn respect to the ultimate metabolic fate of
chemicals taken into the body.  Another source of variation in humans
with th    SS1C S^eCiC individualit7 of each person in comparison
of thf " rajher. unJlf,OHB §enetic background of test animals, even chose
of the  random bred" category.  Since the susceptibility to teratogenic
stimuli appears to have a genetic component in humans, the presencfof
genetic diversity is a further complicating issue in the use of
Sck Wlf. terat°10gy data' f°r estlaation of such a risk in humans


      Thus,  although the  methods of detection of  potential teratogenic
 agents  have merit,  at  present there appears  to be no clear correlation
 between teratogenesis  data for humans and that for experimental  animals.
 Accordingly, man  has no  alternative but  to take  a conservative approach
 toward  exposure  to  chemicals  during pregnancy.

      With the  above precautions,  the risks associated with teratogenesis
 can be  examined  as  shown in the general  flow chart of Figure  7-6.
 Following in depth  examination of human  data, if any,  including
 studies on related  chemicals, in  vivo and in vitro,  laboratory
                                  r-49

-------
 I
Ul
o
                  Are there
                   human
                    data?
                                                     Are there
                                                   experimental
                                                       data?
                                                                     Structure
                                                                      activity
                                                                    relationships
                   Exposure
                  to known
                concentrations?
  Are there
epidemiological
    data?
   Human
data on related
  chemicals?
                                              Assess
                                             reliability
                                                   Evaluate studies
                                                                                Evaluate assays
                                                                                                     Extrapolation to humans
                                                                                                            f possible
                                                                                                                                     Only very
                                                                                                                                     qualitative risk
                                                                                                                                     assessment
                                                                                                                                     statement
                                                                                                                                     possible
                          Risk Estimates
                                          FIGURE 7-6   FLOW CHART FOR TERATOGENICITY RISK EVALUATION

-------
experimental data can be examined and evaluated.  High reliability and
certainty is given to animal studies in vivo, with caution to extrapola-
tion to humans as indicated above.  In many cases, only qualitative
estimates of risk will be possible for teratogenesis.

     Fetotoxicity and Other Reproductive Effects


      The interrelationship among lethal action upon the embryo, maternal
toxicity, and teratogenic effect is complex and the distinction of one
type of effect from another is not always clear.  Until recently,
reproductive hazards have not been considered in depth by scientists,
industry, and regulatory agencies.  A major obstacle in resolving this
problem is the serious lack of clear scientific knowledge about toxic
agents that affect reproduction.

      The reactions of an embryo to a particular chemical depend on a
number of factors:  species differences involving absorption, metabolism,
excretion rates, distribution  and concentration of a chemical in maternal
body tissues, transfer across the placenta, and the kinetics of a
chemical in the embryo-placental unit.  In addition, maternal adaptation
to prolonged exposure and the adequate concentrations of the chemical
during organogenesis, contribute to the problem of predicting effects
in man on the basis of tests in other mammalian species.

     Single generation studies include reproductive, teratologic, and
postnatal effects resulting from exposure to a particular chemical.
The study of fertility and general reproductive performance includes
effects on gonadal function in both sexes, mating behavior, estrous
cycle, and early stages of gestation.

     In order to study the long-term effects of chronic exposure to a
chemical where concentration  may be a factor, the single-generation
study may be extended for several generations into a multigeneration
study.  The toxic responses are reported as a series of indices for
each generation.  The fertility index or conception rate represents the
percentage of matings that result in pregnancy and is affected somewhat
by the fertility and libido of the male.  The gestation index is an
indication of the number of litters that contain live pups.  It is an
incomplete measure of fetal mortality unless the entire litter is
stillborn.   The sex ratio gives an estimate of the relative fitness of
each sex and viability and weaning indices are used to measure the
ability of pups to survive.


     Many of the problems cited in the teratogenesis section on extrapo-
lating experimental data from laboratory animals to man are also relevant
to the analysis of the potential embryotoxic and reproductive effects of
environmental agents on man.   Epidemiologic data in humans  are generally
unavailable since exposure is frequently unsuspected or difficult  to
quantitate.   A notable exception is the fetal alcohol syndrome.
                                  7-51

-------
a
      Various forms of the pollutant may have different effects, even in
 single species of experimental animals.  For example, Table 7-15 gives
 results of a study of the effect of copper salts on pregnant golden
 hamsters.   Copper was given intravenously on day 8 of gestation.  Copper
 in chelated form (as citrate)  was more embryopathic than uncomplexed
 copper (as sulfate)  although the embryocidal activities were similar.

      One must be very cautious in attempting to relate fetotoxic and
 other reproductive effects in  inbred laboratory animals to similar effects
 in a heterogeneous human  population.   However,  positive findings in several
 laboratory species would  suggest the possibility of similar effects in man
 particularly if the metabolic  pathways of the chemical in humans and the
 laboratory animals are  similar.

      Chronic Functional Disorders

      Chronic functional disorders include irreversible changes  resulting
 from intermittent  or continual exposure  to low  levels  of  a pollutant that
 result  in  detectable detriments  in  functional capacity (pathological,
 physiological,  biochemical,  behavioral),  the  ability of'the organism'to
 maintain homeostasis, or  to  compensate  for a  treatment-induced  enhanced
 susceptibility  to  the deleterious effects of other  environmental insults.
 Although all  significant  toxic effects are of concern, a  reversible
 functional  effect, although  undesirable, would be of vastly  less
 consequence  to man than the  development of an irreversible  functional
 effect.  In  addition, most human  exposures to environmental  pollutants
 are  typically long'term exposures to low ambient concentrations,  and,
 therefore,  chronic functional effects may be the most x^idespread
 consequence of exposure to these compounds.

     The ideal data  for assessing the significance of a chemical as  a
 cause of chronic human disorders; would be the results of chronic
administration of measured amounts of pure chemical to human subjects
by the appropriate route.   Since these data are  not likely  to be avail-
able, one must consider whatever human data are  available, data  from
laboratory animals, and, when there are no relevant data for the chemical
of interest itself, data for similar chemicals.

     In all, six types of  data may be used in assessing the risk of
chronic functional disorders:


      (1)  human -  chronic exposure;

      (2)  human -  subchronic exposure;

      (3)  animal - chronic exposure;

      (4)  animal - subchronic exposure;

      (5)  human or animal - acute exposure;

      (6)  extrapolation from other chemicals.


                                    7-52

-------
       TABLE 7-15.  EXAMPLE OF PRESENTATION  OF  TERATOGENESIS  DATA—EFFECTS  OF COPPER SALTS IN  HAMSTERS
I
Ul
Dose
Lc-ve 1
(mi-.Cu/kfO
as Copjn>r Sul fate
J. 13
4.25
7.5
10.0
as Copper Citrate
0.25-1.5
1 .8
1 .2
4.0
No.
Mothers
Treated

16
3
3
2

13
6
8
2
No.
Gestation
Sacs

210
49
30
maternicidal

172
81
99
maternicidal
No.
Living
Embryos (%)

155 (74)
7 (14)
0 (0)
-

143 (83)
48 (59)
65 (66)
__
No.
Resorp-
tions

55 (26)
42 (86)
22 (74)
-

29 (16)
33 (41)
34 (34)
_
No.
Abnormal
Embryos (%)

12 (6)
4 (8)
_
'

A (2)
14 (17)
35 (35)

       f^lf!U'.°AS.^demlneralized waterj^

          0.5-1.0
          mJ/IOOg
10
125
                                                                 115 (92)
                                       10 (8)
                                         0 (0)
        Source:  Perwak, J. et a1.   An exposure and risk assessment for copper.  Flnal Draft

                 Report.  Contract  EPA 68-01-3857.   Washington, DC:  Monitoring and Data

                 Support Division,  Office of Water  Regulations and Standards, U.S. Environmental
                 I'lotection Agency; 1980.

-------
These types of data are listed in order of the priority that should be
given to their evaluation.  Figure 7-7 presents in flow chart form a
general procedure for incorporating the best available data into an
assessment of chronic functional effects.  The least desirable pathway
is the one based upon physical or chemical properties and/or structure
activity relationships.  Figure 7-8 is a schematic diagram showing in
greater detail the evaluation process that might be followed for a pollu-
tant to which humans are exposed by dermal contact.

     In evaluating data on chronic effects,  the questions one wishes to
answer are as follow:

     (1)   What is the  dose?

     (2)   What are the localized effects specific to the route of entry?

     (3)   What are the specific:  characteristics of route of entry,  bind-
          ing, absorption,  distribution and  elimination of this  chemical?

     (4)   What are the chronic systemic health  effects?

     (5)   What are the characteristics  of  systemic absorption, distri-
          bution  and elimination of  this chemical?


     Although human data are the most desirable and present the most
secure basis  for answering these questions,  these data are frequently
anecdotal descriptions of chronic diseases stemming from long exposure
to partly identified mixtures of chemicals.   The symptoms are frequently
thought to be associated with particular chemicals, but careful analysis
may show that the association has not been substantiated.   In addition,
complex behavioral and dietary practices and the intrinsic genetic
individuality of each  person complicate estimates of risk associated with
a particular chemical.  Very few pathological states are unique and
the pathognomic symptom is rare  indeed.  Thus,  for example, demonstration
of cardiomyopathy among individuals exposed  to  a particular chemical
does not necessarily implicate that chemical in the initiation of the
effect.
     In the event that sufficient information is not available from
chronic human exposures, one passes to the next most acceptable data
groupings, subchronic exposures and acute exposures.

     Data from occupational exposures to a chemical are frequently
very valuable.  The exposures tend to be chronic, and the chemical agent
may be well identified.  Documentation of these factors is very valuable.
These data need to be carefully scrutinized since the occupational
history of any individual may include many different exposures and other
predisposing factors need to be evaluated.
                                 7-54

-------
- J
 I
Ul
Ul
               Arc theie
                human
                 data?
                                                                                   Are there
                                                                                 experimental
                                                                                    data?
                                                                         Structure
                                                                          activity
                                                                        relationships
                                           Are there
                                       epideiniological or
                                         occupational
                                            data?
Quantifiable
 exposure?
   Human
data on related
  chemicals?
                                            Assess
                                          reliability
                                                                                 Is extrapolation
                                                                                  appropriate?
                                                       Is extrapolation
                                                         appropriate?
                                                                                                       Extrapolation to humans
                                                                                                              if possible
                                                                                                                                         Only very
                                                                                                                                         qualitative
                                                                                                                                         statement
                                                                                                                                         possible
                                                       Risk Estimates
                           FIGURE 7-7   FLOW CHART FOR GENERAL EVALUATION OF CHRONIC FUNCTIONAL DISORDERS

-------
 I
Ul
a.
mmAji DATA ANJMA1. DATA
-1 	 „ CHRONIC
1 1
SKIN
CIIKONfC
	 1~\ Is there .|uantitation 	 , .,_ Ts there ...,.i,,. Ir.-.ri,.- L_
|^ Of dOSe?
ZYes
Ho
Are there Are there
data on systematic
local 	 ,. absorption
hind ing and d.ila from
luciahnl i sm?
J J'"
(Distribution |
Are there ami eliiulna-
lucal | t n>n d.ua?
effects? 1
, I Systematic I
health
|_ effects? 1
/^
Combine with acute
health effects from
other exposure routes -I
"L"
Is> extrapolation
i 	 1
Yes
ASSti
	 *~ of dose? |
/ Yes
r -^— ,
Are there 1
data on j Are there
lucal ,J syGtenaric
binding and ahaorjn ion
metahol ism? data?
-j..; ZE:
Distribution
Are Uvre andelimiua-
lo(al l Inn ii.ua?
health ~T "
effecis? |
1 — 	 I :>y.sl IMIUL li:
1 lii-.il Hi
1 t-flecth?
Combine with acute 1
1 health effects from
1 olhi'i exposure routes 1
1
1 	 1
la extrapolation 1
appropriate? 1
• V HO
Yes | 	 * 	 1
Obtain
better 1
(data 1
	 1
>S RISK


Nl
H
n

MATIIKMA'riCAL MODEL
SKIN
CHRONIC



	 1.
Is there a mo. 1. 1 ..
of f-kin^ 1
absorption ? j
Yea
I Is the Nn
1 model validated?
Yes
Yes Is extrapolation | Nn
appropriate?


WORST CASE ASSUMPTION
SKIN
CHRONIC
1 Worst case 1
*^jdnse asbumptinn I

v Can dose assumption
1Ki- b(, juat|fled» i H«>


(obtain
I better
Lddla 	
Worst case
abtnrpt j.-.n
assumpt ion
r*"
1
1 Can absorption No
assuiupt ion be
YeJ |~ « 	 .
	 | I Obtain 1
I better 1
data 1
                                  7-8.   ,,,,-s, „,.,; ,.«„„„:„,. rc.u r.v.M HATUW OF  DATA ON CHRONIC FUNCHUNA,.  DISOKDLRS Rt
                                                                                                                           c  FROM DERMA,. ABSORPTION

-------
     Human accidental  exposure  data  are not necessarily  predictive  of  the
 potential for  chronic  functional  disorders.   These  exposures  are not
 often  quantitated and  they are  most  often  single, acute  events.  There
 is no  certainty that  the  target organs  that show pathological changes
 resulting from a single high  dose exposure will  be  the target organs
 that are most  often affected  by a repeated lower dose.   Epidemiologic
 studies, in  general, serve to corroborate  the findings of more specific
 animal or human work,  but  only  infrequently define  cause and  effect
 relationships.

     Frequently the available data for humans are very much less useful
 than would be  expected.  They provide descriptive clues  suggesting
 critical organ  systems but are  insufficient to characterize quantitatively
 the relationship between exposure and effect.

     Thus, animal data are frequently the  only source of information
 available for assessing potential for chronic human impairment.  Some
 of the problems  in the use of animal data  are relatively easy to
 predict and  are  the same as those mentioned previously for other health
 effects:  extrapolation from  laboratory animals  to man must be accomplished
 by use of a  scaling factor to compensate for  body weight differences
 or surface area  differences.  In  some cases,  differences in life span
 present problems.  Behavioral patterns may introduce difficulties in
 generalization between animal and human reactions to a chemical, as will
 subtle  anatomical differences.  For example,  the structure of the rodent
 respiratory  system is such  that nose breathing is obligatory—in humans
 this is not  the  case.   The result is a significant difference with
 certain chemicals in the exposure producing toxic effects due to the
 protection of the rodent lung by  the extremely efficient nasal
 filtering systems.  Recognizing anatomically determined differences
 between man  and  test animal requires biological sophistication and a
very cautious approach to extrapolation.

     The other major problem  of extrapolation of animal data  to humans
 stems  from possible species differences in metabolic pathways.  If  it
 can be  demonstrated that a  chemical is absorbed, stored, metabolized
 and excreted by  the same pathways in animals and man, one can expecc
 similar toxic consequences.   If the pathways or conversion rates or ex-
 cretion patterns  are very  dissimilar, one should expect different and
 usually unpredictable toxic consequences, in which case,  the  animal
 studies would be  an inappropriate basis for making predictions of the
 effect  in man.

     A common problem with animal data is that fairly often a response
 is species specific.   A treatment-related response may be evident in
rats and monkeys, but not  in dogs, rabbits, etc.   If biochemical path-
way data are unavailable to explain the diversified response,  the'con-
servative approach is ordinarily espoused.
                                 7-57

-------
      The  final  pathway  shown  in Figures 7-7 and  7-8  is evaluation  of
 data  for  similar  compounds.   In a homologous series  of chemicals,  toxic
 effects are  somewhat predictable for one member  of the series based on
 known effects of  other  members of that series.   In addition, some  work
 is being  pursued  which  would  allow prediction of toxic effect by analysis
 of chemical  functional  groups  (Kramer and Ford 1968).  At  this  time,
 however,  such models do not constitute a validated approach to  predic-
 tion  of human chronic functional disorders.

      After the  best available  information has been assembled from  human
 and animal studies, the potential for a pollutant to cause chronic effects
 can be estimated.  The  prediction of human effects from human data is ob-
 viously more reliable than thai: from animal data.  Although the human dose
 may be poorly defined,  one can be fairly sure that the signs are charac-
 teristic  of man.  Some  parameters, however, are not: easy to interpret.
 For example, changes in organ weight, change in liver enzymes in the
 blood, increase or decrease in a particular antibody, have all  been re-
 ported at some  time.  It may not be possible, however, to determine
 whether these changes are significant precursors to organ dysfunction
 or whether they are meaningless, random deviations.

      Other changes noted in chronic studies are reversible, that is,
 they  will disappear after the termination of the exposures.  Two types
 of effects tend to be reversible:

      (1)  exposures may temporarily modify cell function but fail  to
          cause significant cell death;  or

      (2)  exposures may cause significant cell death in an organ
          capable of regeneration.

     Many cells in the body are essentially in final form (i.e., differ-
 entiated cells that cannot divide  and be replaced), and in limited
 supply.  Chemical exposure that destroys these cells, is  of the greatest
 seriousness.   Perhaps the most well known example is the  heart.   The loss
 of cardiac muscle cells is irreparable and presents serious consequences
 that have been well documented. Other types of cells can be easily re-
 placed.  This includes the fairly  well-known replacement  of nonspecialized
 epithelium,  connective tissue, and blood cells.   It also  includes the
more specific liver parenchyma! cell.   The result is  that a healthy liver,
which is damaged even severely by  chemical insult,  has a  very  good'chance
 of complete recovery.   Thus,  in evaluating toxicity data,  damage to organs
 that have no potential for regeneration  is far  more significant  than
damage to organs that undergo continual  replacement or have a  capacity
 to regenerate when appropriately stimulated.  An assessment of  the ability
of organs to regenerate is shown in Table  7-16.

     Another difference that  determines  the  seriousness of chemical-
 induced organ damage is the degree  of  redundancy in that  particular
organ.  The kidneys have sufficient  structural  excess to  give  entirely
adequate function, even if 50% or  more is  lost.   The  conducting  svstem
                                 7-53

-------
                                                                                 TABLE 7-16.    TISSUE GROWTH CHARACTERISTICS:    VARIOUS ANIMALS
 i
Ln
<£>
                                            ^;?s!^!Mt!*S^^^
                                          -._	iji. ••** w c«
                                          • Wl**. wK.mUlMtf •U«
                                                                                                                                                              • n« Minv^I* "»» U b«« -/.- — -1 Ml« rtMo.al J M».»ua m.«>LrMW i. A*,'. ..,-,*,„.
                                                                                                                                                  »4 ml* |Mi.nmli,iic utr.utl c*lc.a.i«| *. J«4 kr E * M t...d*r|u l.ittllrd
                          uiuwi .ryttHtH,,,..    ittSri'»c* U7g«iy i.. rr»ifc>ni«u7Siri«~s £;ri7^;
                                                                                                                                                              rrKSTIm •>*.. D • lVr7d r ,IF.Y.
                                                                                                                                                               ,' MailOD Jw«i-u»rj»tON «l wuii/f u*mc. accvri M • *nHuib.r ul I., toi* all.rt tat.  f,((angl>unic libx*1 nl cat »*«•»• (•!* M It-tl da,

                                                                                                                                                                \mttnin rr*t..rrJ i,, 44^t  ____    _      _  	

                                                                                                                                                                                	  fS*»fi(iltl* rfipmn-i*f (MMIH h« Inert*•« U •»!* of
                                                                                  CAi.rt"M>>iori%,r.. i»...brri^7ifis^.iniE.7rTi;—
                                                                                    ....ten. MM* <.„,„„..„ ik-rMrt,... ,„„. ™.^ch/m,
                                                                                    t ill* HjriMilruptiji i*u**.l bj, iMrtM* «f *«rcB^tMm


                                                                                  hi r.tta. (oftlc iSn^r**;. 1» *u, ««pwt«tfalf/«rlK

                                         Ciiir-*!.. ^ik ^r.al f^ifci	^^fflLl''"1'*^^'0' ft"U^|^ff.^"J^^^^^

                                                                            ! k4.ck «rv«r.Ht* al
iln>*. cum,,!.!*! ,» u j,t „,,., tlttlnttmr 0, oo,;y,,. „ -|w.

                                         to rr-'-"'/10	f "^? '^^T...«*». .rifirs—} ^rbViTr.^^n.T^ori;. ».fc d. .k*.i-;	
                                         EjJ^p^^                 *:;* r ±: r;:;^^;;j^rAt.y" ^^
                                                                                                                                                                                              «t.l« by lod

                                                                                                                                                                                                           me.*** W.U U U a
                                                                                                                                                                                            pon*T of dl*i.lii* •«• lannalto* BOaMbl. IrttM
                                                       Source:   W.  S.  Spector  (ed).   Handbook of Biological Data.   W.  B.  Saunders  Co.,  Philadelphia  1956.

-------
of the heart has no excess capacity and no alternative.  Again, moderate.
damage to the heart conducting system is likely to have more serious
consequences than moderate kidney damage.

     When a summary of data shown to be relevant has been assembled  it
may be possible to draw conclusions concerning acceptable human exposure
levels.  It may also be possible to draw tentative conclusions about the
serzousness or reversibility of the predicted disease state.   In most
cases, these conclusions will be tentative and will be the result of com-
binations _of human anecdotal data and animal experimental data substantiated
oy epidemiological evidence.   Predictions from chemical structure or cell
culture studies are not likely to give reliable information.
                                  7-60

-------
                             REFERENCES
Adamson, F.; Gilbert, D.; Perwak, J.;  Scow, K.;  Wallace, D.   Identifzca-
tion and evaluation of waterborne routes of human exposure through food
and drinking water.  Draft Report.  Contract EPA 68-01-3857,  Task 4.
Washington, DC:  Monitoring and Data Support Division, Office of Water
Regulations and Standards, U.S. Environmental Protection Agency; Jan. 1980.

Aksoy  M.  Testimony before Occupational Safety Health Administration.
U.S.'Department of Labor; July 1977.  (As cited by U.S. EPA 1978b)

Bridges, B.A.  Some general principles of mutagenicity screening and a
possible framework for testing procedures.  In:  Environmental Health
Perspectives, Experimental Issue No. 6, December , 1973:  pp. 221-227.

Bulsiewicz, H.  The influence of phenol on chromosomes of mice Mus_
musculus in the process  of spermatogenesis.  Folia Morpho.   (Warsz.)
36(l):13-22; 1977.

Crow, J.F.  Impact of various types of genetic damage and risk assessment.
In:  Environmental Health Perspectives, Experimental Issue No. 6,
December,  1973: pp. 1-5.

deSerres,  F.J., and W. Sheridan,  eds.  The evaluation of chemical muta-
genicity data  in relation to population risk.  In:  Environmental Health
Perspectives,  Experimental Issue  No. 6, December, 1973.

Freese,  E.  Thresholds in toxic,  teratogenic, mutagenic and  carcinogenic
effects.   In:  Environmental Health Perspectives, Experimental  Issues No.
6,  December,  1973: pp. 171-178.

Infante, P.F.; Rinsky, R.A.; Wagoner, J.K.; Young, R.J.  Leukemia in
benzene workers.   Lancet 2:76-78;  1977a.

Infante, P.F.; Rinsky, R.A.; Wagoner, J.K.; Young, R.J.  Benzene  and
leukemia.   Lancet  2:867: 1977b.

Leek,  I.   Correlations of malformation  frequency with  environmental  and
 genetic attributes in man.   In:   Handbook of  Teratology, Volume 3,
Comparative Maternal and Epidemiologic  Aspects.

Wilson, J.G.;  Eraser,  F.C.;  eds.   New York, NY:  Plenum Press;  1977:
pp 117-157.

Mahaffey,  K.R.  Quantities  of  lead producing  health  effects in  humans:
 Sources and bioavailability.   Environ.  Health Perspect.  19:285-295;  1977.

 McCann, J.; Choi,  E. ;  Yamasaki,  E.; Ames, B.N.   Detection of carcinogens
 as mutagens in the salmonella/microsome test  assay  of 300 chemicals.
 Proc.  Nat'l Acad.  Sci USA 72:5135-5139;  1975.

                                    7-61

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National Cancer Institute (NCI).  Guidelines for carcinogen bioassay in
small rodents.  Carcinogenesis Technical Report Series No. 1 DHEW
Publication No (NIH) 76-801, Bethesda, MD:  NCI; 1976: p. 46.

Ott, M.G. et al.  Mortality among individuals occupationally exposed to
benzene.  Arch. Environ. Health 33:3; 1978.  (As cited by US EPA 1978b)

Perwak, J.; Bysshe, S.; Goyer, M.; Nelken, L.;  Scow, K.;  Walker, P.;
Wallace, D.  An exposure and risk assessment for copper.   Final Draft
Report.  Contract EPA 68-01-3857.  Washington,  DC:  Monitoring and Data
Support Division, Office of Water Regulations and Standards, U.S.
Environmental Protection Agency; 1980.a.

Perwak, J.; Goyer, M.; Harris, J.; Schimke, G., Scow, K.; Wallace, D.
An exposure and risk assessment for trihalomethanes.  Final Draft Report.
Contract EPA 68-01-3857.  Washington, DC:   Monitoring and Data Support
Division, Office of Water Regulations and  Standards,  U.S. Environmental
Protection Agency; 1980b.

Perwak, J.; Goyer, M.; Schimke, G.; Eschenroeder, A.; Fiksel, J.; Scow,
K.; Wallace, D.  An exposure and risk assessment for phthalate esters.
Final Draft Report.  Contracts EPA 68-01-3857,  5949.  Washington, DC:
Monitoring and Data Support Division, Office of Water Regulations and
Standards, U.S. Environmental Protection Agency; 1981a.

Perwak, J.; Goyer, M.; Nelken, L.; Scow, K.; Wald, M.; Wallace, D.  An
exposure and risk assessment for mercury.   Final Draft Report.  Contracts
EPA 68-01-3857, 5949.  Washington, DC:  Monitoring and Data Support
Division, Office of Water Regulations and Standards, U.S. Environmental
Protection Agency; 1981b.

Perwak, J.; Byrne, M.; Goyer, M.; Lyman, W.; Nelken, L.;  Scow, K. :
Wood, M.; Moss, K.  An exposure and risk assessment for dichloroethanes.
Final Draft Report.  Contracts EPA 68-01-5949 and EPA 68-01-6017.
Washington, DC:  Monitoring and Data Support Division, Office of Water
Regulations and Standards, U.S. Environmental Protection Agency; 1982a.

Perwak, J.; Goyer, M. ; Nelken, L; Payne, E. ; Wallace,, D.   An exposure and
risk assessment for lead.  Final Draft Report.   Washington, DC:  Monitor-
ing and Data Support Division, Office of Water Regulations and Standards,
U.S. Environmental Protection Agency; 1982b.

Report of a Committee of the European Environmental Mutagen Society.
Mutagenicity screening:  general principles and minimal criteria.  Mutation
Res. _53_:361-367;  1978.

Scow, K. ,; Thomas, R.; Wallace, 'D.; Walker, P.; Wood, M.   An exposure and risk
assessment for pentachlorophanol.  Final Draft  Report. Contract EPA 63-01-
3857.  Washington, DC:  Monitoring and Data Support Division, Office of Water
Regulations and Standards, U.S. Environmental Protection Agency; 1980.
                                  7-62

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 Scow, K.; Goyer, M.; Payne, E.; Perwak, J.;  Thomas, R.;  Wallace, D.;
 Wood, M.  An exposure and risk assessment for phenol.  Final Draft
 Report.  Contract 68-01-3857.  Washington, DC:  Monitoring and Data
 Support Division, Office of Water Regulations and Standards, U.S. En-
 vironmental Protection Agency; 1981.

 Simms, H.S.  Pathology of Laboratory Rats and Mice.  Oxford Publications-
 1967: pp. 733-747.

 Snyder, C.A.; Goldstein, B.D.; Sellakumar, A.R.; Bromberg, I.; Laskin,
 S.;  Albert, R.E.  The inhalation toxicology  of benzene:   incidence of
 hematopoietic neoplasms and hematoxicity in  AkR/J and C57BL/6J mice.
 Toxicol. Appl.  Pharmacol. 54:223-331;  1980.

 Symons, J.M.; Bellar, T.A.; Carswell,  J.K. DeMarco, J.;  Knopp, K.L.;
 Robeck, G.G.; Seeger, D.R., Slocum,  C.J.;  Smith, B.L.; Stevens,  A.A.
 National organics reconnaissance survey for  halogenated  organics.   J.
 Am.  Water Works Assn. 67:634-646;  1975.

 Thomas, R.; Byrne,  M.;  Gilbert D.; Goyer,  M.   An exposure and risk
 assessment for  trichloroethylene.  Final Draft Report.   Contract EPA
 68-01-5949.  Washington,  DC:   Monitoring and  Data Support Division,  Office
 of Water Regulations  and Standards, U.S.  Environmental Protection Agency
 1981.

 U.S.  Department of  Agriculture (U.S. DA).  Food consumption  of households
 in the United States.   Spring 1965.  Report No.  11,  Food and  Nutrient
 Intake of Individuals in the  United States.   Stock  No. 0100-1599.
 Washington, DC:   U.S.  Government Printing  Office; 1972.

 U.S. Department of  Agriculture (U.S. DA).  Food  consumption,  prices,
 expenditures.   Agricultural economic report no.  138,  Supplement  for
 1976.   Washington,  DC:  USDA;  1976.

 U.S. Department  of  Agriculture (U.S. DA).  Nationwide  food consumption
 survey  1977-1978.   Preliminary Report No.  2.   Food and nutrient  intakes
 of individuals  in 1 day  in  the United States,  Spring  1977.  Washington,
 DC:  Science  and Education Administration, U.S. DA; 1980.

 U.S.  Department of Health, Education and Welfare  (U.S. HEW).  Community
 Water Supply  Study, Public Health Service, Environmental  Health Service.
 Bureau  of Water Hygiene; 1970.

 U.S.  Environmental Protection Agency (U.S. EPA).  National Organics
Monitoring Survey.  Unpubl. Washington, DC:  Technical Support Division
Office of Water Supply, U.S. EPA; 1978a.

U.S.  Environmental Protection Agency (U.S. EPA).  Estimation of population
cancer risk from ambient benzene exposure.   Washington, DC:  Carcinogen
Assessment Group, U.S.  Environmental Protection Agency;  1978b.
                                   7-63

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U.S. Environmental Protection Agency (U.S. EPA).  Water quality criteria
documents availability.  Federal Register.  45(231):79318-79384-
November 28, 1980.


U.S. Food and Drug Administration (U.S. FDA).  Compliance program evalu-
ation FY 1974.  Total diet studies.   Washington, DC:   Bureau of Foods
U.S. FDA; 1977.


Venugopal, B. and T.D. Luckey.   Metal ToKJcity in Mammals.  2. Chemical
toxicity of metals and metaloids.  New York,  NY:  Plenum Press- 1978-
pp. 24-32.


Williams, R.T.  Detoxification Mechanisms. 2nd ed.  New York,  NY:
John Wiley and Sons,  Inc.;  1959: pp.  390-409.


Wilson, J.G.  Current status of teratology.   In:  Handbook of  Teratology.
Volume 1, General Principles and Etiology. Wilson, J.G.;  Fraser  F.C •
eds.  New York, NY:   Plenum Press;  1977:  pp.  47-74.
                                 7-64

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            8.0  EXPOSURE AND EFFECTS—NON-HUMAN BIOTA
 8.1  INTRODUCTION

      Although the principal focus of the exposure and risk analyses per-
 formed for the Office of Water Regulations and Standards has been on humans,
 it is important to consider the exposure of fish, other aquatic organisms,
 and wildlife to waterborne pollutants and the adverse effects of pollutants
 on these species for several reasons:

      (1)  they may be part of the human food chain and/or of economic
           importance to man;

      (2)  they may be threatened or endangered species;

      (3)  because of a pollutant's critical environmental pathways or
           fate, its environmental impact may be on non-human rather than
           human receptors;

      (4)  assessments and regulatory recommendations of  others  may over-
           look significant  environmental effects unless  the hazards and
           risks to non-human species are considered; and

      (5)  they may serve as warnings or indicators of an environmental
           problem when media concentrations  are low or non-detectable.

      As  in evaluating human risks,  exposure  and effects  for other
 species  should be considered together .   Since the risk to a species is  a
 function of  both the  exposure  to  a pollutant  in a sufficient quantity or
 for  a sufficient duration to elicit  adverse  effects,  the  risk will  be small
 despite  the  potential toxicity of  the pollutant.   Similarly,  exposure to
 high concentrations or  quantities  of a  pollutant  will  not result in
 significant  risk unless  adverse effects  can  result  from  these exposure
 levels.   In  general,  effects data  for aquatic organisms and  wildlife
 are  more readily available  than information on  exposure.  A  large number
 of laboratory  investigations have  been  conducted,  correlations have
 been developed  for factors  such as bioaccumulation, and field or model
 ecosystem  studies have been conducted for many pollutants and species.
 For  most priority pollutants, the results of acute and chronic bioassays
 on a  limited number of species are available and  published in the EPA
 Criterion Documents.

      In evaluating environmental effects, there are problems inherent
 in extrapolating from laboroatory data to field conditions.   Unlike
 controlled laboratory systems, the natural environment is complex "and
multi-leveled,  subject to both regular and irregular changes in its
physical and chemical make-up.  Habitats even of the same tvpe (e.a.,
cold-water streams) may differ significantly in certain important °
variables.
                                  3-1

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Many of these variables may significantly increase or decrease the con-
centration of a pollutant that triggers an adverse effect.  For example,
differences in pH, hardness, temperature and other aspects of water
chemistry may cause different effects from those detected in a simple
laboratory test at the same "total" pollutant concentration.

      Evaluation and  quantification of  exposure has  its  own difficulties
 since one must  know  both the  population distribution and habits  of the
 species  of concern,  in addition  to the pollutant's  environmental distri-
 bution.   Materials balance  and environmental  pathways data provide in-
 formation on  pollutant concentrations  and distribution.   The exposure  por-
 tion of  the risk analysis should determine as  best  as possible whether
 there is  exposure of  receptors at those locations where  the pollutant
 is  present and,  if so,  the  extent,  duration, and frequency of exposure of
 important subpopulations.   There are only limited data  in the literature
 on  the population distribution of fish,  other  aquatic organisms,  and
 wildlife;  their  potential exposure to  polluted  water  (drinking rates,
 migration patterns in and out of polluted areas) is  even less well known.
 Therefore,  in many cases, estimates or  ranges  of exposure will have to be
 first  developed  or postulated and then  compared with  scattered observa-
 tions  (such as  fish kill reports;)  in order to  see if  they are feasible
 and realistic.

     Although in  principle  all aquatic  species  and other biota that are
 exposed to polluted water should  be examined in risk  analyses, the effort
 and amount of data required generally prohibits such  a detailed analysis.
 Therefore,  the exposure and effects analysis can be concentrated  on:

      (1)   sensitive species representative of each species category;

      (2)   species known to inhabit geographical regions  or habitats
          where  the pollutant is  present;

      (3)  species for which adequate effects or distribution data  exist;

      (4)  aquatic organisms, particularly fish.

Historical information on the long-term discharge patterns of the  pollu-
tant is important in order to examine the adaptation of resistant  strains
in  the species present or shifts   in the specres composition of the local
community.  Information on wildlife—both exposure  and effects data—is
usually less common than for fish and other  aquatic  organisms.   Also,
livestock are not usually considered in this  part of a risk analysis'be-
cause they are rarely exposed to  lethal levels of a  pollutant.   Instead,
livestock are much more likely to concentrate pollutant  levels in  their
tissue and the potential exposure to this accumulation is a human problem.
In a similar manner,  accumulation in edible  aquatic  species is addressed
in  the human exposure section, drawing upon monitoring and biological  fate
data.  In cases where there  is some understanding of the relationship  be-
tween body burden and toxic  effects levels, bioconcentration may  be
addressed in the biotic effects  and exposure  chapter.  Otherwise  it is
discussed under biological fate  in the  environmental pathways  chapter.


                                   8-2

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 8.2  GOALS AND OBJECTIVES

 8.2.1  Exposure Analysis

      The goals of analyzing the exposure of non-human species are to
 determine or estimate the significant exposure routes and the extent to
 which aquatic organisms are exposed to pollutant concentrations in water
 sediment and other organisms,  and the extent to which terrestrial organisms
 are exposured to pollutant concentrations in soil,  air,  water and/or
 other organisms.  Exposure routes include ingestion,  inhalation,  and
 dermal absorption.  The extent can be defined in terms of the length
 of time during which populations are exposed, the geographical area in
 which exposure occurs,  and the degree of exposure of  an individual or
 community.   The degree  of exposure may be expressed as the concentrations
 to which the organisms  are exposed or their daily intakes times
 and absorption efficiency.

      Ideally,  the  results of the exposure analysis  for non-human  biota
 include:

      •   Identification  of geographic areas  with  pollutant concentrations
         in  the water  or other  significant media  (sediment,  soil)  high
         enough to  have  deleterious  effects  on biota in order  to identify,
         geographically,  subpopulations  at risk.   (Monitoring  data may
         reveal actual areas, and potential  areas  may  be  indicated by  the
         presence of sources of  pollutant  releases.)

      •   Identification  of communities or  particular species—size or
         number,  location (geographical  or habitat-specific)—exposed  to
         the  pollutant.

      •   Evaluation of behavior  patterns  (e.g., migratory, reproductive,
         age-linked) of biota that may  increase  or  decrease the potential
         for  exposure.

      •   Identification  of  time-dependent  patterns of pollutant  availa-
        bility  (persistence, seasonal fluctuations, etc.) and comparison
        with species  activity patterns.

      •  Evaluation of the existence of mitigating or exacerbating environ-
        mental parameters that can affect pollutant toxicity and  the likeli-
        hood of their presence in areas or habitats in which environmentally
         significant pollutant concentrations are  known or estimated.

8.2.2.  Effects Analysis

     The objectives of the effects portion of risk analyses for non-human
biota are:
                                    3-3

-------
 (1)   Identification of those  concentrations  or  ranges  of  concentrations
      at  which a pollutant  may have  deleterious  effects on aquatic and
      terrestrial organisms.

 (2)   Identification and  evaluation  of  these  effects—acute,  chronic,
      reproductive—as  a  function of exposure  levels, time, etc.

 (3)   Identification of factors  that influence the availability and
      degree of impact  of the  pollutant on biota.

 The results of the  effects analysis should be compatible  with the
 results  of the exposure  analysis in terms of  how the levels  are quantified
 so that  the risk to aquatic and terrestrial organisms  can be ascertained.

 8.3  APPROACHES  AND METHODS

 8.3.1  Overview

     In  undertaking  an exposure and effects analysis for  non-human species,
 one could begin  either with developing an understanding of exposure of
 aquatic  or terrestrial organisms and then consider the effects of  such
 exposure, or begin with effects and  then consider exposure.

     In  the first approach, one would rely primarily on the  results of  the
 materials balance,  monitoring data, and the environmental pathways analysis
 to identify the media and types of  habitats in which exposure can  occur.
 their geographical  distribution, and the concentrations and  durations
 associated with  exposure, and then  seek to establish the  species or
 communities in those areas most likely to be exposed.  Effects analysis
 would then focus on  selected species or communities.,  evaluating the
 potential acute or  chronic effects  resulting from the estimated exposure
 levels.  This approach has the advantage of limiting detailed consider-
 ation of effects to  those species and populations for which exposure is
 anticipated or known, thereby limiting the scope and effort of the
 effects  and analysis.  The disadvantage,  of course,  is that one may only
 give detailed consideration to exposure of certain populations for which
 significant effects of the pollutant are not likely to occur, or to
 organisms for which  the effects of the pollutant are  unknown.

     Alternatively, in beginning with effects analysis, one first identifies
 toxic concentration levels by examining a number of laboratory studies
 for a range of species and then seeks to  determine the geographical areas
and real situations where the sensitive species  or communities may be ex-
posed to levels sufficient to give harmful effects.   This  method also has
advantages and disadvantages  similar to those described above.

     For practical reasons, it would seem appropriate to use  both
approaches concurrently,  with the goal of quickly focusing on the exposure
conditions of significance and on sensitive organisms.   However,  as
                                  3-4

-------
indicated in the introduction to this section, data on the harmful effects
of pollutants are more readily obtained by traditional methods of litera-
ture review and analysis, whereas exposure analysis may require a more
lengthy analysis and inputs from monitoring, fate and pathways, and
materials balance studies (tasks that may be proceeding concurrently).
Therefore, most exposure and effects analyses for non-human biota are
likely to begin with development of an understanding of potential effects
and then proceed to development of understanding of exposure situations.

     Figure 8-1 gives a schematic representation of the methodology used
for this analysis.  Note the close interaction with the other portions of
the risk analysis.

8.3.2  Effects Analysis

8.3.2.1  Data Collection and Preliminary Data Review

     The first step in analyzing aquatic effects is to collect readily
available data on the pollutant under study.  The amount and type of
data readily available depends upon the pollutant being examined.  If
the pollutant is well known and effects have been documented, priority
can be given to review articles and data compilations [such as the EPA
Water Quality Criterion Documents (e.g., U.S. EPA 1980a, b)]; however,
this reliance on secondary sources must be complemented by review of
original publications to clear up errors and contradictions between
studies that may arise.  If the effects of the pollutant have not been so
well studied and reviewed, then more effort must be devoted to search for
published data.  In addition,  persons currently conducting research on
the pollutant may be contacted.

     Data should be collected  from both laboratory studies measuring the
effects of the pollutant on various aquatic organisms and field investi-
gations or case studies documenting actual effects of the pollutant in
the environment.  Several information sources can be used:

     •  EPA sources—materials in the MDSD priority pollutant file;
        e.g.,  criterion documents,  NRC reviews,  fish kill data, EPA-
        published reports from field laboratories,  etc.

     •  Computerized literature  search in conjunction with the human
        effects studies using  TOXLINE,  Chemical  Abstracts, Pollution
        Abstracts,  Bio  Abstracts,  etc.

     •  Formal literature search—this is a second stage search,  which
        involves retrieval of  pertinent literature  cited in the first
        sources obtained,  and  hand  search of  selected  journals,  e.g.,
        Pesticide Monitoring Journal,  Environmental Contamination and
        Toxicology,  etc.,  which  are likely to contain information on
       environmental pollutants.

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                             EFFECTS ANALYSIS
                                                                                                    EXPOSURE ANALYSIS
             Input From I
             Fate and   I
             £u t hways_	j
Oi
                              Data Collec-
                              tion and Pre-
                              liminary Data
                              Review
                                  I
                                                                       Identification
                                                                       of Sensitive
                                                                       Species and
                                                                       Their Ranges
Critical Data
Review and
Tabulation
Input from!
Monitoring
                                   Inputs From
                                   Materials
                                   Balance
Identification
of Areas Where
Concentrations
are Expected or
Measured t" be
High
                              Summary of
                              Effects
                              Concentra-
                              tions and
                              Influential
                              Parameters
                                                    I  Input  From
                                                      Fate and
                                                      Pathways
                                                      Analysis
                                                    Identification
                                                    of Factors
                                                    Modifying Avail-
                                                    ability of
                                                    a Pollutant at
                                                    a Measured
                                                    Concentration
                                                  j	
                                                           Identification of Loca-
                                                           tions  or Categories of
                                                           Locations Where Risk to
                                                           Aquatic  Organisms is
                                                           Likely to Occur
Input
From
Monitor-
                       FIGURE 8-1  FLOW CHART OF METHODOLOGY  FOR EFFECTS  AND EXPOSURE ANALYSIS  FOR NON-HUMAN BIOTA

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     If information on effects of a pollutant  is not  available,  the
effects analysis must be bypassed because,  in  general, no method exists
for estimating toxic effects.  If information  on a structurally  similar
chemical is available, it should be examined but not  considered  to be  sur-
rogate data for  the risk analysis since  the relationship between structure
and toxicity is relatively unknown, making  tentative  any extrapolation
from one chemical to another.  In the absence  of effects data, the re-
search required to assess the toxicity of the  pollutant (using standard
aquatic species and testing procedures) should be recommended.

8.3.2.2  Critical Data Review and Tabulation

     The second step of the effects methodology is to review critically
the data collected and tabulate effects concentrations, in addition to
consideration of the variables influencing  these values.

     Before the effects data are compiled, however, monitoring and fate
and pathways analysis results (or preliminary results) should be
reviewed.   First, one should consider pollutant environmental concen-
tration ranges available from the monitoring section to determine
whether the pollutant is likely to have:

     (1)   no effect on aquatic organisms;

     (2)   some effects on certain sensitive species;

     (3)   effects on most species; or

     (4)   effects on all species, as a first approximation.

Second, a  review of effects data and the initial results of fate and
pathways analysis can identify critical parameters influencing availa-
bility of  the pollutant to biota (e.g. ,'pH, hardness, temperature).
These considerations will help limit the scope of and define the remain-
der of the effects analysis.

     In the data review, pollutant concentrations that have been
reported to have lethal and sublethal effects  on aquatic organisms
are examined.   Either previously compiled data or the results from the
publications collected in the literature search, organized into  tables
that present species and effects levels in order of increasing concen-
tration, are used.  Each result must be reviewed for its scientific
validity and data with serious flaws (e.g., faulty control, death of
test subjects due to other causes, or lack of replication)  rejected,
unless no  other information is available; in which case,  the weakness
should be  highlighted.

     The data are typically divided into several categories to facilitate
comparison:  fish and aquatic invertebrate species,  freshwater and
saltwater  species, marine and estuarine species, lethal and sublethal
effects,  and chronic and acute effects.   Important parameters influencing
the effects at different concentrations are reported,  when  available,
                                 3-7

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 for each experiment.  These parameters include pH, temperature, water
 hardness, type of bioassay (static or flow-through), type of water and
 time of exposure.  Tables 8-1, 8-2, and 8-3 are examples of effects
 data tabulated from risk assessments for phthalate esters, zinc, and
 mercury (Perwak, _et_ al. 1981a, 1980, 1981b).

      Exposure of aquatic organisms to the pollutant via gill absorption
 is the major focus of the effects analysis for non-human biota.  However,
 depending on the availability of information and relevance to the pollu-
 tant of concern, several other categories of effects must be considered
 in this portion of the analysis:

      •  Toxicity of the pollutant to aquatic organisms  through the
         route of ingestion.

      •  Toxicity to terrestrial species,  both (1)  plants through root
         uptake of pollutants  in soil and aerial deposition and (2)
         animals (usually avian and mammalian wildlife species)  through
         ingestion of  contaminated biota,  water or  dermal contact with
         soil.


  _    Data  on these subjects are developed and presented  in a manner
 similar to  that for aquatic organisms.

 8.3.2.3 Summary of Effects

      The environmental  factors  that  potentially  affect uptake and
 toxicity ot  the pollutant are discussed either,  through  summarising
 research indicating key  factors  (e.g., species groups, water hardness
 duration) influencing  the toxicity of the  pollutant or,  if  that
 is not  possible,  by compilation  of results of a  number'of  separate studies
 in which important  factors have  riot been  controlled for.  The importance
 of these factors  in the  degree of  impact  of the  pollutant on the environ-
 ment  and the likelihood  of their existing at sites where significant
 concentrations  of the pollutant  are found is discussed.

      In many cases the information on the effects of  the pollutant is
 insufficient to prioritize available data relative to their relevance to
 risk analysis.  However, if possible, it is practical to consider effects
 in the following general order.  When data are available, chronic effects
 (which usually occur at lower  concentrations) have priority over acute
 effects for persistent pollutants to which long-term exposure is likelv
For short-lived pollutants (e.g., highly volatile compounds) focus
should be placed on acute effects; however,  if releases are on a continu-
ous basis,  then chronic effects should also be considered.   Effects on
fish and shellfish have priority over effects on other invertebrate
species because of their greater potential for ingestion bv humans.
                                  8-8

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TABLE 8-1.   EXAMPLE OF ACUTE EFFECTS DATA FOR FRESHWATER FISH--PHTHALATE  ESTERS
                                   Exposure Through Mater
Conctntrttlon
Comound (m/1 )
Di-o-butvi • 731
phchalate
1.2
1.3
2.91
6.47
10.0


Di(2~schylhexyl) -005
phchalace


.014



> 10.0

100.0


Butvlbeazyl *3-3
phchaiace
445.0
Diechyl 29-6
phchalata
96.2
DiaeciivL 49.5
phehaiatc
it 58.0

Species
_E_^M.S»
Blueglll
(lepc«rls aacrocM rui 1
•
Fathead NlnnoH
(Plaephales prom las)
Channel Catfish
(Ictalurus punctatus)
Rainbow Trout
(Salao oalrdnerl)
Blueglll
(LepQBTts. macrochlrusl


Rainbow Trout
(Sal mo galrdnerD






Fish1

Blueqlll
(Lepomli inacrochl rus )


Blueglll
(l»poiii
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                                    TAWJi 8-2.  EXAMPLE OF CIIRONIC/SUIU.ETHAL DATA FOR FRESHWATER FISH—ZINC
oo
Cone .
(ppb)
•>.f>
")]
106
180
187
260
640
852
Species Compound
Rainbow trout ZnSO,
(SujLjno galrd_neri)
Flagfish adults (females) ZnSO
(.lordanella florldac-) *

Fathead minnow Zn+f
(Plinephales prpmelas)
Fatliead minnow ZnSO
4
Chinook salmon Zn++
Kalnbow trout ZnSO
4
Hi'uuk trout Zn-H-
llardncss Tent
(mg/1) Duration Effects
13-15 20 mln. Threshold avoidance
level
44 100 days Crowth rt-diu-i-d
'•6 ? Effect on growth,
duct ion In 11 fe-
cycle test**
2 42 days Chronic bioassay
6. A mortality
3-1(> 6.9 mortal Ity
44 ? Effect on growth
survival, or repro-
duction In life-cycle
test**
Source***
Sprague (1968)
Speh.ir (1976)
lie-no it and
Hal combe*
Brunga (1969)
Chapman (1978)*
Sinley et al.
(1974)
,llolcooie et al.
(1978)*
              **
                The value represents the geometric mean of the levels at which there effects are observed.   In  the  case
                of embryo-larval tests the geometric mean la divided by 2 to obtain a value comparable  to  life-cycle  studies.
             ***Sei- sourcu indicated below for references.

             Source:  I'erw.ik, .1. et  ul .   An  exposure  and  risk assessment  for zinc.   Final Draft Report.  Contract
                      T.l'A 68-01-3857.  Washington,  DC:  Monitoring  and  Data Support  Division,  Office of Water
                      (Manning  and  Standards,  U.S.  Environmental  Protection Agency;  1980.

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                   TABLE 8-3.  EXAMPLE OF LOWEST REPORT MERCURY EFFECTS DATA FOR AQUATIC ORGANISMS
        Form of
        Mercury
                Freshwater
               Invertebrate
                                           Lowest Reported Effect Level (ug/1)
  Freshwater
     Fish
   Marine
Invertebrate
Marine
 Fish
        Inorganic     0.9a  (Daphnia
                            magna)
                                   (Salvelinus
                                     fontinalis)
                       5 b (Pseudocalunus
                            mi nutus)
                           10  (Fundulus
                                heteroclitus)
oo
I
                       5  (Daphnia
                            raagna)
33.Ob (Salmo           3.6C (Mysidopsis
        gairdneri)            bahia)
                                                                                    200  (Fundulus
                                                                                           heteroclitus)
Organic      O.la  (Daphnia      0.04b (Salmo           1.2a (Mysidopsis
                     magna)              gairdneri)             bahia)
                                                                                           125a (Fundulus
                                                                                                  heteroclitus)
                                         5.1° (Salmo
                                                gairdneri
                                                        150  (Gammarus
                                                               duebeni)
       a
        chronic value

        Sublethal effect
       c
        Acute value

       Source:   Perwak,  J.,  et  al.  An  exposure and  risk  assessment  for  mercury.   Contract  68-01-5949.
                Washington,  DC:   Office of Water  Regulations and  Standards,  U.S.  Environmental  Protection
                Agency;  1981.

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Lethal effects and reproductive impairment effects have priority over
sublethal effects—e.g., avoidance behavior and physiological changes—
because of their known adverse impact on receptor populations.

     To summarize the effects section, individual species, species groups,
and age groups that are most sensitive to the pollutant are distinguished,
along with the importance of other environmental parameters, in order to
identify specific subpopulations of aquatic organisms; that are likely to
be at higher risk.

8.3.3  Exposure Analysis

8.3.3.1  Introduction

     Analysis of the exposure of aquatic organisms is generally more
qualitative than quantitative in nature.  This is due to the difficulty
of reliably estimating biota populations and their distribution on a
national, or even regional, scale.  Without this information, quanti-
tative exposure models are not useful.  As described previously, exposure
analysis depends on the input of data from other portions of the risk
analysis.

     Effects data point ouc the pollutant levels with significant bio-
logical impact and, therefore, better define the boundaries of the ex-
posure analysis for the pollutant.  This can also aid in organizing
monitoring data retrieval from large data bases (e.g,, STORET).  Effects
data are also useful in the initial part of exposure analysis in identi-
fying those species and their habitats on which to focus efforts, as
suggested by results indicating most sensitive species or identifying
environmental variables conducive to pollutant availability.

     Monitoring data are very important to exposure analysis.  Pollutant
concentrations in different environmental media or good estimates of
concentrations are required before effects data obtained in the labora-
tory can be evaluated for their relevance to natural  conditions.  Without
knowledge of a pollutant's environmental concentrations, the risk to
aquatic species cannot be estimated; effects data only satisfy one-half
of the data requirements.  For this reason, monitoring data should be
collected with the sensitivity of non-human species in mind in order tc
facilitate exposure analysis.  The focus can be on significant exposure
pathways (e.g., surface water) and pollutant concentrations (e.g., greater
than a minimum effects level).

     Environmental fate and pathway information is significant in the
exposure analysis when used in conjunction with monitoring data.  Under-
standing of the pollutant's behavior in the environment can indicate the
biological availability of the pollutant in environmental media to which
biota are exposed.  For example, if the fate data, indicate a low free
fraction of a pollutant at high water hardness or a tendency for adsorp-
tion, this information can be used in the qualitative interpretation
                                   8-12

-------
 of pollutant concentrations reported in monitoring programs as "total"
 levels, i.e., in assessing pollutant availability to and potential
 effects on aquatic organisms.  Areas that are likely to have the
 environmental properties that might be conducive to pollutant availability
 (e.g., areas with low water hardness, low concentrations of complexing
 agents) can be identified through information from the fate analysis.
 If more specific monitoring data (e.g., dissolved or available concen-
 trations) are available, these can be used to corroborate inferences
 about types of habitats with a high exposure potential.

      In the absence of monitoring data, fate and materials balance in-
 formation may permit estimation of ambient concentrations through the use
 of fate models (e.g., EXAMS, fugacity models).

      Materials balance information can also be used together with monitor-
 ing data to identify geographic areas where exposure of aquatic organisms
 is likely to exist due to the presence of releases.  Because of its
 general nature,  it is more useful for indicating areas (regions, river
 basins, etc.) likely to have high pollutant concentrations relative to
 other comparably sized areas than for targeting specific potential
 problem sites.

      Since the  focus of the risk analysis process is often national
 rather than local,  the monitoring data collected and used represent
 large areas (usually no smaller than a minor river basin).   Therefore,
 the monitoring  data are not likely to directly corroborate  the
 fate and materials  balance  analyses due to  differences  in scale  or
 rounding off.  As  a result,  quantitative analysis (e.g.,  implementing
 speciation models  on total  metal concentration)  is  not  possible  because
 of requirements  for site-specific input data.

      Other types of information useful in analysis  of non-human  exposure
 as a confirmation of monitoring,  fate,  and  materials balance data,  in-
 clude fish kill data and  site-specific  investigations of  the effects  of
 the pollutant in the environment.   Ideally,  fish  kill data provide  in-
 formation  on  types  of  sources,  locations, and  temporal  distribution of
 pollutant  concentrations  actually observed  to  have  lethal effects on
 biota in the  field.   Information that would  help  interpret these results
 is  usually  not available.   Field  studies  are likely to  be more detailed
 and to measure parameters influencing  the pollutant's behavior at the
 site  of investigation but, because of  the specificity of  each study and
 the usual  short time span of investigation,  the generality of these
 studies is  limited.  It is unlikely there will be studies on all eco-
 systems or biotic communities of  significance with respect to a particular
 pollutant.  Despite  the inherent  weaknesses in and specificity of these
 data, they may serve to confirm or tie together independent pieces of
 information from other sections of the risk analysis.

     The following sections describe the steps of the exposure analysis
depicted in Figure 8-1.
                                   3-13

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 8.3.3.2  Identification of Sensitive Species

      If sufficient data from the effects analysis are available, the
 first step in exposure analysis is to identify those species most sensi-
 tive to the pollutant (e.g., salmonoids) and to determine their range
 (nationally distributed or locally found).   In many cases, however
 either data are not available for many species or the differences in
 sensitivity among species is not great enough (perhaps due to a very
 limited data base) to justify 'separate treatment of sensitive members.
 When this is true, concentrations of the pollutant in water are identified
 that are likely to cause deleterious effects on each group of aquatic
 organism (e.g., marine fish,  freshwater invertebrate).   Table 8-4 is an
 example of how these data may be organized  (Scow et al.  1981a).

 8•3•3•3  Identification of Areas with Expected or Measured High
          Concentrations                             ——       a_

      This second step is approached  in one  of two ways,  again depending
 on  availability of data.   The first  approach is  to use monitorin* data
 fior example, from the STORET data base,  to determine the  location°of  areas
 with  concentrations equaling  or  exceeding the effects levels  set in  the
 Preceding step.   Specific  locations  (e.g.,  a particular  minor river
 basin)  or larger areas of  the U.S.  (the  Northeast)  may be  identified
 according to  the distribution pattern of the particular  pollutant
 Figure  8-2  (Perwak et al.  1980)  is an example of  one method by which
 monitoring  data  may be organized  for  exposure analysis.  If few  monitor-
 ing data  are  available,  other information on the  distribution of primary
 sources and usage  patterns  (from materials  balance  or environmental  path-
 ways  analysis) or  fish kills  (see Table  8-5,  Scow et. al. 1981b)  can  be
 used  to identify locations where high pollutant concentrations mav be
 found.

 8-3.3.4   Identification of Factors Modifying Availability

    _For certain pollutants, data from the environmental pathways analysis
 can indicate qualitatively what fraction of pollutant concentration  in
 water is actually available to aquatic organisms.  For example,   for many
 heavy metals, factors such as hardness and PH may significantly  alter the
 effective concentrations causing deleterious effects.  Monitoring data
 can be better interpreted through understanding these influential variables
 even  in a qualitative way.  The STORET data base includes the distribu-
 tion  of water hardness and other chemical parameters on a national basis
 and these characteristics can be combined with data on the pollutant
 concentration distribution.  As an example,  Table 8-6  lists the  major
 river basins that meet zinc concentration and hardness criteria  indicat-
 ing a risk to aquatic biota (Perwak et al.  1980).   Since  the methods  with
which data are aggregated regionally for each factor are  not always
equivalent, quantification of fie relationship through techniques'such as
regression analysis has noc been possible up to this time.
                                  8-14

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            TABLE 8-4,
 Silver
Concentration
 EXAMPLE OF  RANGES  IN EFFECTS LEVELS
 FOR  AQUATIC  BIOTA—SILVER

                  Effect	
<0.1 ug/1

0.1-1.0 ug/1
1.2 ug/1
2.3 ug/1 (maximum at
any time)

1-10 ug/1
13  ug/1



10-100 ug/1
100-1000 ug/1
>1000 ug/1
No effects reported for any  species

Chronic effects on most sensitive  freshwater
fish (mortality of trout in  soft water) and
invertebrates (mayfly LCso).  Acute effects on
most sensitive marine invertebrates.   (Sea
urchin egg development.)

EPA criterion to protect freshwater aquatic
life at water hardness of 50 mg/1  as CaC03.

EPA criterion to protect saltwater aquatic
life from acute toxicity.

Acute effects on most  sensitive freshwater
vertebrates (guppy)  and  invertebrates (daphnia),
The typical concentration  range for chronic
effects on freshwater  vertebrates and inver-
tebrates.   Chronic effects on most sensitive
and typical marine invertebrates.

MA criterion to protect freshwater aquatic
life at water hardness of  200 mg/1 as CaC03.
Most reported effects  levels for freshwater
vertebrates and invertebrates fell within this
range.  Chronic effects  (growth retardation)
on freshwater algae.   Typical range for acute
effects on marine invertebrates.

Includes the highest concentration reported to
cause acute and chronic effects on marine
invertebrates.   (Shrimp LCso at 262 ug/1 and
no spawning at  103 ug/1).  Sublethal effects
noted for marine algae in 4 days.

Includes the maximum reported concentration
causing acute effects  on freshwater invertebrates.
(1400 ug/1.  reported for rotifer LCso) and
chronic effects on algae (freshwater)  (toxic
at 2000 ug/1).
Source:   Scow,  K. et  al_.  An exposure and  risk assessment for  silver.
          Contracts  EPA 68-01-5949,  6017. Washington, DC:  Office of Water
          Regulations  and Standards,  U.S. Environmental Protection
          Agency; 1981.
                                      3-15

-------
                                    TABLE 8-5.  EXAMPLE OF DATA ON FISH  KILLS—PHENOL
        Dale
             Water Body
                                            Location
                         Number
                         Killed
Source
Co
I
cr>
5-25-71      Roaring Brook

6-8-71     -  Casey Fork  Cr.
8-6-71       Tunungwant  Cr.

8-6-71       Tunugwant Cr.
8-6-71       Allegheny R.
1971         Ohio R.
1971         Milwaukee R.
1972         Severn Run  (Branch)
1973         Kingsland Cr.
5-18-74      llardisty Pond
5-22-74      Banmers Pond
6-18-74      Red Clay Cr.
6-19-74      New Haven Harbor
7-29-74      Black Warrior R.

6-17-76      Black Rock  Harbor
        6-22-76      Bridgeport  Harbor
        11-17-76     Great Miami R.
        r>/6         Bear Cr.
        5-10-77      Hebble Cr.
        6-1-77       Sanders Br.ineh
        B-2-77       Beaverdam Cr.
Glastonbury,  CT

Mt. Vernon, IL              6.000
Bradford,  PA                53,000

NY, near Bradford, PA       45,000
Irvine Mills, NY           62,000
New Martinsville,  WV        5,000
Gratton, Wl                 1,500
Odenton, MD                   100
Lyndhurst, NY               5,000
Southbury, CT                 550
Naugatuck, CT                 010
Newcastle, DE               2,000
New Haven, CT              20,000
Tuscaloosa, AL             10.700

Bridgeport, CT             25,000
                                    Bridgeport, CT             20,000
                                    Ohio                        0.848
                                    Fail-view. PA               28.000
                                    Greene Co., OH              1.000
                                    Hampton, SC              Tot ;i)
                                    Damascus, VA                  150
High phenol, Zn, Cu in fish tissues
No toxics measured in water
Wood preservation
Discharge for chemical industry
in area
From Bradford, PA
From Bradford, PA
Phenols from nearby chemical industry
Phenols, oil from storm sewer (?)
Phenols from plastics industry
Phenolic discharge from chemical  industry
Mixed solvents, heavy oil, and phenol
Asphalt and phenol
Haveg Industry phenol spill
High phenol, Al, pll, BOD, and collforin
17,000-21,500 Ib  phenol spill by
Reichhold Chemical
Chemical, textile, metal industries, and
POTW nearby: high phenol,  Cu,and  Zn
in fish tissues
Discharges from POTW, power plant
Metal and cyanide production
Phono I;;, rvanidrs from agric.  operations
"Government operations"
Railway phenol spill
Discharge by American Cyanamid
        Source:  Scow,  K. et al.   An exposure and risk  assessment  for phenol.   Final  Draft Report.   Contract
                 68-01-5949.   Washington, DC:   Office of  Water Regulations  and Standards, U.S.  Environmental
                 Protection Agency; 1981.

-------
GO
      Source:
                  STORE! SYSTEM

               2IHC:  OBSERVATION /  ACUTE  CRITERIA
               75TH  PERCENT HC5

                ft  . ™ .0  ;«::
                ft  j ox: ?3  j 03;;
                M      '   i 033:
               iiO'f.t -1 .00;;;: ?!• ;;o 03 r:iil'ln(1
,  J. et al.  An exposure  and  risk assessment for zinc.   Final Draft  Report

                                 of
                                                                                                 Contract
                  FKJURE 8-2  EXAMPLE OF CRAl'HIC PRESENTATION OF OVERLAP BETWEEN  OBSERVED

                              CONCENTRATION AND WATER  QUALITY CRITERION FOR THE PROTECTION
                              OF AQUATIC LIr-'E-- ZINC

-------
                                  TABLE 8-6.   EXAMPLE OF CONSrnERATION OF UNAVAILABILITY OF
                                              OBSERVED CONCENTRATION OF ZINC IN SURFACE WATER
CO
I
GO
              River Basin
           Major/Minor Name

 1/9    Merrlmack  R.
 1/14   Presumpcot  R.  4, Casco Bay
 1/24   Lake Champlaln
 2/8    Delaware R. -  Zone  4
 2/15   Rappahannock & York Rivers
 5/2    Monongahela R.
 5/3    Beaver R.
 5/7    Kanawlta R
 5/13   Miami R.
 5/21   Ohio R., main  stem  &  trihs
 6/3    Cuyahoga R.
 6/13   Detroit
 7/2    Hudson Bay, Rainy River  (23/02)
 7/3    Upper portion,  upper Mississippi R.
 7/6    Lower portion,  upper Mississippi R.
 7/12   Mississippi, Salt Rivers
 7/16   Fox R.
 7/19   Meramec R.
 8/3    Menominee
 8/24   Green Bay,  W.  Shore
 8/49   Calumet-Burns Ditch Complex
9/i4   S.  Central  Missouri R.
9/7    Big Sioux R.
9/12   Lower Missouri R.
Zinc
N
126
24
10
305
296
331
25
338
86
257
21
9
5
135
189
9
24
1 f\
H£
50
42
42
70
Mean Zn
>120 ppb
A
*
*
A
*
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
^50% of ppb
observations
>120 ppb Zn

A
A
A





A


A









                                                                                            of ppb
                                                                                        observations
                                                                                       >300 ppb Zn
           ^50%  of  hardness
           Measurements  <5Q  ppm
                                                                                            A
                                                                                            A
                                                                                            A
A
A


A
A
A
A
A
A
A
A
A
A
A


A
A
                                                     37
           Source:
                                                  aml »sk assessment f°r zinc.  Final Draft Report.  Contract

-------
 8 • 3.3.5   Identification of Locations in Which Risk to Aquatic  Organisms
          is  Likely to Occur

      The  final  step  in the biotic  effects  and exposure analysis  is  to
 summarize the results of the  two sections  to indicate areas where a
 significant  exposure potential  exists.   Areas may be regional (e.g., the
 Northeast) or categorical  (e.g., at  the mouths of major rivers)  depend-
 ing on the data base and other  factors  discussed  previously.   In addi-
 tion, exposure  may vary temporarily  if  discharge  patterns  are seasonal,
 if certain age-groups of a species are  more  sensitive (these  also vary
 seasonally), or if certain seasonal  environmental processes  (e.g.,  spring
 rains) increase the  availability of  a  pollutant.

 8.3.4  Terrestrial Effects  and  Exposure Analysis

     Although most of the  information described here  is  concerned with
waterbome routes of  exposure to priority pollutants,  terrestrial systems
should also be  considered  for those situations in which  a pollutant" is
directly  applied to plants  (e.g., as a  herbicide, seed fungicide) or for
pollutants that are likely  to be distributed  on or be disposed of in the
soil and  expose plants  through root uptake.   Effects on  plants, as well
as those  on higher members of terrestrial food chains  (e.g., pheasants)
should be considered when data are available.  The effects and exposure'
analyses  for these terrestrial species are usually very brief, at most
indicating sites (e.g., vicinity of manufacturing plants, landfills)
where exposure  of terrestrial biota may occur and the range of possible
effects.   Discussion of environmental factors determining exposure
levels (e.g., leachability of pollutant, soil pH)  should be included when
applicable.
                                 8-19

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                              REFERENCES
Perwak, J; Goyer, M.;  Nelken,  L.;  Schimke,  G.;  Scow,  K.;  Walker,  P.;
Wallace, D.  An exposure and risk assessment for zinc.   Final Draft
Report.  Contract EPA 68-01-3857.   Washington,  DC:  Monitoring and Data
Support Division, Office of Water Regulations and Standards,  U.S.
Environmental Protection Agency;  1980.

Perwak, J.; Goyer, M.; Schimke, G. ; Eschenroeder, A.;, Fiksel, J.;
Scow  K.; Wallace, D.   An exposure and risk assessment for phthalate
esters.  Final Draft Report.  Contracts EPA 68-01-3857,  5949.  Washington.
DC:  Monitoring and Data Support Division,  Office of  Water Regulations
and Standards, U.S. Environmental Protection Agency;  1981a.

Perwak, J.; Goyer, M.; Nelken, L.; Scow, K.; Wald, M,.; Wallace, D.
An exposure and risk assessment for mercury.  Final Draft Report.
Contracts EPA 68-01-3857, 5949.  Washington, DC:  Monitoring and Data
Support Division, Office of Water Regulations and Standards, U.S.
Environmental Protection Agency;  1981b.

Scow,  K.;  Goyer, M.; Nelken, L.;  Payne, E.; Saterson, K., Walker, P.;
Wood   M.;  Cruse, P.; Moss, K.  An exposure  and risk assessment for
silver.   Final Draft Report.   Contracts EPA 68-01-3857,  5949 and EPA
68-01-6017.  Washington, DC:   Monitoring and Data Support Division,
Office of Water  Regulations and Standards,  U.S. Environmental Protection
Agency;  1981a.

Scow,  K.; Goyer, M.; Payne, E. ; Perwak, J.; Thomas,  El.;  Wallace, D.;
Wood   M.   An exposure  and  risk assessment  for phenol.  Final Draft
Report.   Contract  EPA 68-01-3857. Washington, DC:  Monitoring and Data
 Support Division,  Office of Water Regulations and Standards, U.S.
 Environmental Protection Agency;  1981b.

U.S.  Environmental Protection Agency (USEPA).  Ambient water quality
 criteria for chlorinated benzenes.   Report No.  EPA 440/5-30-028.
 Washington, DC:   Criteria  and Standards Division, Office of  Water
 Regulations and  Standards, U.S.  Environmental  Protection Agency;  1980a.

 U.S.  Environmental Protection Agency (USEPA).   Ambient  water quality
 criteria for chlorinated ethanes.  Report  No.  EPA-440/5-80-029.
 Washington, DC:   Criteria and Standards Division,  Office of  Water
 Regulations and Standards, U.S.  Environmental Protection Agency; 1980b.
                                   8-20

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                         9.0   RISK CONSIDERATIONS
 9.1   INTRODUCTION

      In  the previous sections of this  report, goals and objectives, methods
 and approaches have been presented  for evaluating  the characteristics of
 a pollutant—the sources of its release  to the environment, its pathways
 and distribution in the environment, and its exposure and effects on humans
 and other biota.  Each of these components is important in its own right;
 yet for  the regulatory agencies, as well as the public, it is essential
 to integrate them in order to establish, as best possible, the current or
 potential impact of the pollutant on man and his environment.  Thus one
 needs to establish a "bottom line"  for the analysis—how much of a problem
 is the pollutant, what are the risks associated with each increment in ex-
 posure to the pollutant, and how do the  risks compare with those of other
 pollutants?  The answers to these questions place  risks and problems asso-
 ciated with the pollutant in perspective, so that  they can be evaluated
 and acted upon, if necessary, by the parties involved.

     In other research on the risks of environmental pollutants, the term
 "risk assessment" has been given two general interpretations.  First, it
 has been used to connote a broad assessment of the overall risk associated
 with a pollutant, including risk to humans, fish and wildlife.  Second, it has
 had a narrower meaning, namely the  quantitative human health  risks asso-
 ciated with a pollutant, often as a result of documented or estimated
 carcinogenicity or mutagenicity (e.g., the extrapolation of laboratory
 animal data on carcinogenicity to humans).   In this report, the term "risk
 considerations" is used to signify the evaluation and integration of the
 information on the pollutant for the purpose of yielding an understanding
 of the nature and extent of risks to humans and other biota associated
with the pollutant.

     More specifically, the "risk considerations" portion of the risk
 assessment should answer the following types of questions:

     •  Does  the pollutant cause  a significant  increased health risk to
        the general  human population?

     •  Does  the pollutant cause  significant increased risks  to general
        populations  of  fish,  shellfish, wildlife  and  other  aquatic species?

     •  What  is  the  nature of  the  increased  risks?  Can  the  risks  be
        quantified?  What  are  the  risks to  the  general population  groups?

     •  Are  there  identifiable  subpopulations based on geography,  age,
        sex,  lifestyles,  etc.,  for whom the  risks are  higher  than  those
        of  the  general  human population?  What  is the  range of risks  for
        different  subpopulations?

-------
     •  What are the key components of, or contributors to, increased
        risk for both general and specific subpopulations of humans and
        other biota?

     •  Are there environmental or other factors that can mitigate the
        extent, severity, or consequences of the risks attributed to the
        pollutant?

     •  What are the sources and environmental pathways to which signifi-
        cant widespread risks to humans and other biota can be attributed?

     Quantitative answers to all of these questions would be desirable.
Practically, this may not be possible because of the lack of data on ex-
posure or effects of a pollutan:, the uncertainties in existing data and
the lack of agreement on methods to define and quantify risk.  Thus only
in the very best of circumstances will there be data of sufficient quantity
and quality to specify the actual and potential risks associated with a
specific pollutant.   More likely, ranges of estimated risks will have to
suffice.  However,  formal analysis of risk can indicate areas for addi-
tional data development,  identify the areas of the greatest uncertainties,
and point the direction for possible measures to reduce risk,  if needed.
9.2  GOALS AND OBJECTIVES

     The overall goal of this portion of a risk assessment is to develop
a qualitative and/or quantitative understanding of the nature, extent,
and severity of the risks imposed by a pollutant on humans,  fish, wildlife,
and other biota.  A subsidiary goal is to establish the sources, pathways,
or causal factors associated with these risks so that control actions
for risk reduction can be identified and evaluated, when such are required.

     For a given pollutant (or family of pollutants)  specific objectives
for this work include:

     (1)  Estimating the average health risks to the general human popula-
          tion, based upon average exposure ana the range of health effects
          associated with the pollutant.

     (2)  Identifying those human subpopulations—on the basis of age,
          sex, geographic location, occupation, lifestyle, or other
          descriptors—that sustain greater than average risks, and
          estimating the extent and severity of the health risks asso-
          ciated with the pollutant.

     (3)  Estimating the average risks to general populations of fish,
          shellfish, other aquatic species and wildlife based upon
          average exposure and the range of effects associated with
          the oollutant.
                                    9-2

-------
      (4)   Identifying  the  subpopulations  of  fish,  shellfish,  other  aquatic
           species  and  wildlife—by  geographic  location,  species,  habits
           and  other  descriptors—that  sustain  higher  than  average risk,
           and  estimating the extent and severity of the  risks to  these
           sub-populations  associated with the  pollutant.

      (5)   Identifying  the  sources,  pathways, and causal  factors asso-
           ciated with  risks  for human  and other species  in order  to
           allow investigation of possible methods  for risk control  or
           reduction.

      (6)   Presenting the information on risks  in a manner  that is informa-
           tive and understandable to technical and non-technical  audiences.
 9.3  APPROACHES AND METHODS

 9.3.1  General Considerations

 9.3.1.1  Definitions of Risk

     Risk may be defined as the potential for negative consequences of
 an event or activity.  In the context of assessment of risk from environ-
 mental pollutants, the event or activity is the release of a pollutant
 into and its subsequent traverse through the environment such that humans
 and other biota are exposed, and the negative consequences are any ad-
 verse effects on the exposed populations.  Thus, if a pollutant is be-
 lieved to be harmful and if it is present in the environment, there is
 certainly a potential for exposure and subsequent harm; that is, some
 risk exists.  The purpose of the risk considerations portion of risk
 assessments is to go beyond such a qualitative statement of potential
 risk, by estimating or measuring this potential.

     Although the nature of adverse effects may be well  understood, the
 key difficulty in risk estimation lies in determining the probability
 that adverse effects will occur.  The probability is comprised of two
 factors:

     •  The likelihood that groups of organisms will be exposed to various
        levels of the pollutants.

     •  The likelihood that exposed organisms will experience adverse
        effects.

 These two factors correspond to the two major branches of investigation
 described in previous sections—exposure and effects.

     Analyzing the probability of adverse effects of different pollutants
will present different types of problems,  depending upon pollutant  proper-
 ties and effects.   For a highly persistent  substance that is  present in the
                                  9-3

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human diet and known to have long-term effects, the main challenge lies
in estimating the likelihood of adverse effects based upon observed
exposure levels.  On the other hand, for a substance that is degraded
rapidly and appears only in scattered locations, but is known to be an
acute toxicant, the focus should be on estimating the likelihood of
exposure.  Therefore, the risk estimation methodology must be flexible
enough to encompass these and a multitude of other situations.

     For a population of susceptible organisms, risk may be expressed
in several ways.  One can state the probabilities that certain fractions
of the population will be adversely affected (e.g., 5% chance that 9/10
will be affected, 20% chance that 1/3 will be affected).  This sort of
quantitative estimate is usually difficult to achieve.  Alternatively,
one can state the expected number that may be affected, allowing a cer-
tain margin for error to reflect uncertainties in the underlying data
(e.g., 200,000 + 50,000).  Finally one can give an order-of-magnitude
estimate that has no real measure of confidence attached to it (e.g.,
at most 5% will be affected).  Each of these ways of expressing the
degree of risk can be more detailed in terms of types of effects, e.g.,
the chance of a specific disease, premature death, extent of disability,
etc.

     Hence, risk estimates may be classified into three types, correspond-
ing to decreasing level of precision with which the  population at risk
and the degree of risk can be characterized.

     •  probability distribution,

     »  numerical interval, and

     •  o rder of magnitude.

     The level of precision of a risk estimate cannot exceed the precision
of the exposure and effects data from which it is obtained.  In cases
where probabilistic risk estimates cannot be obtained, it may be possible
to develop a range or numerical interval of risks.  In other cases, lack
of data may preclude any process ether than the mosst general or compara-
tive estimate of risk.

9.3.1.2  Overview of Evaluation Approaches

     An evaluation of the risk.3 associated with an environmental pollutant
will usually consist of more than one result;  it will describe the spec-
trum of risks identified in a variety of different cases characterized
by features such as:

     •  nature of the adverse effect,

     •  subpopulations affected, and

     •  temporal aspects  (e.g., frequency).
                                  9-.1

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     Often different receptor populations will be exposed in different
ways over differing periods of time, and will experience different
effects as a result.  The spectrum of such risks must, therefore, be
described to the extent permitted by the available data on exposure and
effects, developed according to the methods of the preceding sections.
For some pollutants, these data may not be sufficient for quantitative
estimates, and consequently the risk assessment may be only qualitative.
However, even with incomplete data, it is often possible to make meaning-
ful statements about risk.

     An overview of an approach for guiding the risk estimation process
is shown in Figure 9-1.  As shown, effects and exposure are first con-
sidered in parallel.  Then, depending upon the level of precision with
which effects and exposure can be quantified, the results are combined
into one of four possible outputs.

     For considering health effects, the first task is to review effects
data for the pollutant in order to ascertain whether toxic  levels can be
quantified for specific toxic effects.   The methods for dealing with
chronic or acute effects are substantially different; they  have been
discussed in Section 7.0,  and will be explored further below.   The level
of precision of the toxicity estimates  will determine the attainable
level of precision for the resulting risk estimates and will likely be
different for each category of toxic effect.

     Exposure data are also reviewed in order to  ascertain  whether exposure
can be quantified,  and to  select  a suitable level of precision for combin-
ing exposure with effects  data.

     There are four distinct possible outcomes of this procedure:

     •  Neither effects nor exposure are quantifiable.   A qualitative
        indication of  risk may be  given if  the nature of the effects,
        the  predominant exposure  routes,  and  populations  at  risk can
        be identified  (output  4 on Figure 9-1).

     •  Only exposure  is quantifiable.   By  making conservative  assump-
        tions  about effects  levels,  a hypothetical  discussion  of potential
        risks  is  possible.   Thus,  if  a  risk indeed  exists, one  can at
        least  identify  the  subpopulations that would  be most severely
        affected  (output 3  on  Figure  9-1).

     •   Only effects are quantifiable.   In  this case, by postulating
        realistic exposure  levels,  one can  discuss  the risk  that would be
        present under various  exposure scenarios  (output 1 on Figure 9-1).

     •   Both effects and exposure  are quantifiable.  This is the only
        output  for  which a detailed and quantitative assessment  of  risk
        would be possible.   By combining estimates of exposure and
        toxicity with information  about the size and distribution of the
                                   9-5

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cute
                                                                  Is
                                                                exposure
                                                              quantifiable
    la
  toxlclty
uuautlf table?
Compute dose-
response re-
lationships
. .^
Ill'tl'l IN ill.:
levul ..f
ptOCl !• JOI1
k
//
Discuss riak lor
liyjx:tlietlc.il
1
/
/
\
Coir.blae
, 1— _ effects an it
exposure
est Imntes
1
Assess rJ.-ilc for
sub pcpuliit Ions
exposed by
varjoiiti routes
•>
\
\
-— —

Dlscusa risk under
conservative
assuirpc Ions
about effects

(Hvo qunlltat tve
indication of
possible risk
 FIGURE  9-1.   FLOW CHART FOR  DEVELOPING RISK CONSIDERATIONS

-------
        populations at risk, one can express numerically the risks to
        different receptor categories, including the specification of
        exposure routes, geographic extent, and frequency that character-
        ize these risks (output 2 on Figure 9-1).

     Although the discussion above suggests a straightforward approach
to estimation of risk according to four possible schemes, practical con-
siderations complicate the actual risk estimation.  First, some health
effects may not be quantifiable in sufficient detail for numerical analysis,
whereas others may be.  Discrepancies may exist among data on effects or
there may be a widespread distribution of effects among different sub-
populations.  Second, exposure may not be quantifiable in sufficient
detail for numerical analysis.  It may be possible to quantify exposure
for certain subpopulations and not for others; or the size of various
subpopulations may not be known.  Thus, for any pollutant, one can expect
that there are many exposure/effects combinations (potential risks) that
can be considered only qualitatively, though some quantitative expression
of risk may be possible for some exposure/effects combinations.

     The risk estimates obtained through these procedures should be quali-
fied by two important types of information:  the assumptions incorporated
into each estimate, and the degree of confidence attached to numerical
estimates.  Furthermore, any risk analysis should indicate what additional
data are required either to improve accuracy or precision or to confirm
certain assumptions.

9.3.1.3  Approaches Described in the Literature


     Within the past few years,  there has been considerable interest by
regulators,  regulated industries,  and the public in methods for esti-
mating risks,  particularly the risks to human health.   The setting of
tolerances for pesticides in food or feed, instituted in 1947,  re-
quired consideration of exposure and effects to develop safe levels of
pesticide residues.   The Delaney Amendment to the Pure Food and Drug Act
required a different approach, by setting a zero tolerance for food ad-
ditives that contained substances carcinogenic to experimental animals.
In 1976, the federal government suggested procedures and guidelines for
health risk assessment of suspected carcinogens (U.S. EPA  1976).
Albert _et_ al.  (1977) suggested a rationale for assessment of carcinogenic
risk developed by the Environmental Protection Agency.   In 1977, a com-
mittee of the National Academy of Sciences dealing with safe drinking
water discussed evaluation of risk of carcinogenicity and recommended
the linear extrapolation approach to low doses (NAS  1977).

      The  Environmental  Protection  Agency  published  its  approach  to  the  de-
 velopment of  water  quality  criteria,  which  considers quantitative  and qual-
 itative examination of  both human  health  and  environmental  effects  data
                                  9-7

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 (U.S. EPA 1979).  The Interagency Regulatory Liaison Group further dis-
 cussed methods of analysis and extrapolation of health data from labora-
 tory animals to humans (U.S.  EPA 1979b).   Similarly, federal agencies
 have suggested methods for evaluating the risks for air pollutants and
 hazardous waste materials (U.S.  EPA 1978; U.S.  EPA 1979c).


      A number of health specialists have  criticized the inflexible quan-
 titative approach developed by regulatory agencies, and/or suggested
 other approaches to  the evaluation of risk from pollutants (Kensler,
 1979; Gori,  1980; Peto, 1980;  Whittemore,  1980).   Clearly  there is a
 highly volatile controversy over the most desirable and appropriate
 approach to  evaluate the health  risks to  man and other biota.   In this
 methodology,  several  alternative  approaches  are  recommended  for  consider-
 ation.   Depending upon  the  specific  nature of the  pollutant  and  the data
 available on exposure and effects,  one or more  suitable methods  may be
 chosen for use in each  risk analysis.  These methods  should  always be
 selected with a clear understanding of the associated uncertainties and
 assumptions.   The remainder of this  section  discusses in greater detail
 the  possible qualitative  and quantitative approaches  to risk estimation.
 The  reader is  referred  to  the  citations given above and to the appendix of
 this  report  for additional  details  of quantitative risk assessment pro-
 cedures.

 9.3.2  Evaluation of Risk to Human Health

 9.3.2.1  Overview

      Earlier  in this  section,  the goals were presented  for identifying
 and  evaluating  the human health risks  in  a qualitative  and quantitative
 manner  for both the general and special population  groups.   The  pro-
 cedures  used  to  evaluate risks are  the same  for both  the general popu-
 lation  and subpopulations; however,  the exposures may be different  and
 the  resulting risk estimates may differ.

      The  first  step in  considering exposure should be to summarize  the
 exposure of  the  general population and the exposure of  specific  subpop-
 ulations.  The  exposure can be summarized in terms of an average daily
 intake or  dose  for each of several different exposure routes, or the
 total cumulative  exposure from all routes in the form of a daily intake
 or dose,  for  the  average individual.  Alternatively,  the additional ex-
 posure to  specific defined subpopulations can be presented separately as
 average daily intakes for each of the various exposure routes.   These data
will have been  developed from the methods and approaches described in
 Section 7.0.   in addition,  the numbers of persons  in  each of the various
 subpopulations  often  can be estimated. The summary will normally include the
mean or range of daily intake  for the typical person, regardless of geo-
 graphic location, and may include a range based upon age or sex.   Maximum
values or ranges should also be given for selected subpopulations whose
 characteristics result in greater than average intakes.
                                  9-8

-------
       In a parallel  process,  human health effects  of  the  pollutant are
 summarized as  indicated  by the available  data  from humans,  experimental
 animals,  and other test  systems concerning the range  of possible  adverse
 effects.   Finally, data  are considered  from supporting studies  that may
 confirm health effects such as the results of  mechanism of  action or
 pharmacokinetic studies.   To  the extent that the available  data are
 sufficient, no-observed-effect levels  (NOEL) or lowest-observed-effect
 levels  (LOEL)  for different types  of health effects are presented;  gaps
 in  the  data are so identified.   In these  summaries, it is important to
 identify  the exposure routes,  the  dose  levels  for  the  different responses,
 and the species for  which  the  observations were made.

 9.3.2.2  Qualitative Risk  Analysis

      The most general type of risk analysis that  can  be  accomplished  is
 a simple  comparison  of the various exposure levels with the NOEL  or LOEL
 levels.   From  such a comparison, a qualitative indication can be  obtained
 of  the  nature  and types  of risk that persons may incur.   For example,  if
 the lowest acute toxicity  level for a particular functional disorder is
 X mg per  kg body weight  and the average exposure is much  less than  X mg
 per kg  body weight,  the  risk of  large-scale acute  effects is low.   If  on
 the other hand,  a certain  subpopulation is,  or can be, exposed  to levels
 approaching or greater than X,  the members  of  this subpopulation may be
 at  significant risk  of the acute effect. This  type of qualitative compari-
 son places the overall risks in perspective, and indicates the  areas
 (effects  and exposures)  requiring  additional studies or evaluations.
 Since one is not attempting to  obtain quantitative estimates of risk with
 this approach,  "no effects" levels  in laboratory animals  can be compared
 with human exposure  levels  in  order to  identify the potential (not  probable)
 risks to  humans.

      The  degree of  certainty with which these comparisons can be made
 depends upon the precision with which effects  and exposures can be
 characterized.    For  example, the effects can be better defined  if they
 are  based  on human data,  or experimental animal data substantiated with
 appropriate pharmacokinetics and mechanism  of  action data.  In vitro data
 and data  from  cellular studies may also be useful in these simple compari-
 sons in determining qualitatively whether human health effects can be
 anticipated.

      The  qualitative approach to risk assessment,  relying on general
 comparisons of effects and exposure levels, is  used when either both
exposure and effects  cannot be quantified   (output  4 on Figure 9-1) or
exposure can be quantified but not effects  (output  3).   If exposure
cannot be quantified, some hypothetical exposure values can be developed
based upon plausible  scenarios, and these  exposures can be compared with
 "no  effect" or  "lowest effect  levels," as  described above.
                                   9-9

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9.3.2.3  Semi-Quantitative Risk Analysis

       When exposure to the general and specific subpopulations is known,
and effects data are available with some precision (at least for animal
systems), the analysis given above can be extended by consideration of
margins of safety.  In the development of pesticide tolerances and water
quality criteria, the U.S. EPA considers the use of margins of safety to
develop tolerances and criteria for chemicals that are not carcinogenic.
The same approach can be used in risk analysis to obtain a relative rank-
ing of the risks of various subpopulations to specific effects.  The
procedure is simply to match as best possible the NOEL or LOEL with the
exposure levels (by specific route) and to develop a margin of safety by
dividing the exposure level into the effects level.  Ranges in exposures
and ranges in effects levels can also be used in order to determine ranges
in margins of safety.

       The advantage of this semi-quantitative approach is that some
order of prioritization can be made for risks to different subpopulations
and risks of different adverse effects.  For example, a margin of safety
for adults for a specific effect may be 1000, but for children only 10,
if the pollutant exposure is primarily a result of contamination of milk
and the effects levels are based on total body burden or weight.  Alter-
natively,  the margins of safety for those who work in a particular industry
may be many times less than the margins of safety for persons living
near or far from the industry.  Analysis of margins of safety for differ-
ent exposure routes by which the same population group can be exposed
may help to suggest the type of environmental controls that could reduce
the exposure.  In evaluating the significance of margins of safety, one
must bear in mind uncertainties in the underlying data and assumptions,
the accuracy and precision of the exposure levels used, and the relevance
of the available effects data to the possible human exposure and effects.

       Another term frequently used to establish the magnitude of risk
associated with ingestion of an agent is the ADI (acceptance daily intake).
The ADI is an empirically derived value that reflects a particular com-
bination of knowledge and uncertainty concerning the relative safety of
a chemical.  The uncertainty factors (U.F., also called safety factors)  used
to calculate ADI values (NOEL/U.F. = ADI)  represent the level of confidence
that can be justified on the basis of the available toxicological data.
Generally established guidelines for uncertainty factors are 10, 100 or
1000.  When the quality and quantity of data are high, the uncertainty
factor is low and when the data are inadequate or equivocal, the un-
certainty factor must be larger.

       In development of regulations, safety factors from less than 10
to over 10,000 are used in an attempt to reduce risks to negligible or
acceptable values or to balance risks with costs.  In the risk evaluation
process described above, the regulating agencies ara assigned the task of
defining what constitutes acceptable levels of risk since the analysis
attempts only to rank these risks semi-quantitatively.
                                  9-10

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        Table  9-1 illustrates the expression of risk considerations by
 use of margins of safety  (Scow et. al. 1980), as an example of a semi-
 quantitative approach to risk assessment.  The worst case scenario in
 the table would result in an exposure to 3.2 mg/kg per day, providing
 a margin of safety of 1.7 over the lowest reported no-effect level
 (6 mg/kg), which is for fetotoxicity.  Most of the exposure in this
 scenario can be attributed to a spill of PGP.  When the spill is excluded,
 the exposure would be 0.4 mg/kg per day with a margin of safety of 15.
 Other non-occupational exposure routes appear to have a margin of safety
 of at least 200.


      A variant of the semi-quantitative approach may be taken for certain
 chemicals for which there is a significant amount of reliable epidemio-
 logical data or monitoring data and the effects in humans are well
 understood.  For some pollutants, there may be a direct relationship
 between the level of the pollutant in body tissues such as adipose tissue,
 and acute health effects or chronic functional impairment.   Also,  epi-
 demiology studies may provide information to relate exposure or daily
 intake of a pollutant to observed levels in body tissues.   This type of
 information,  when combined with average intakes for the general population
 or specific subpopulations,  can show the potential risk levels  in  sub-
 population groups.   Thus the approach  combines exposure information
 with epidemiology,  bioaccumulation,  and health effects  studies, or moni-
 toring data,  to  predict risk levels for exposed populations.

      An example  of  applying this  approach is  taken from an  assessment
 of risks  associated with lead in  the environment (Perwak et  al., 1982a).
 Tables  9-2  and 9-3 present selected results of a considerable~amount  of
 research  that  has been  done  on  the  epidemiology  of lead exposure and
 effects in  humans.   The  exposure  levels  in  human blood  for various  sub-
 populations and pathways  can be compared directly  with  lowest reported
 effects levels and  no effects levels for humans."  As indicated  by  this
 comparison, humans  appear  to  be at significant  risk of  incurring'adverse
 effects of  lead exposure,  especially children  exposed through ingestion
 of paint  or inhalation  and  ingestion of contaminated dirt and  dust and
 urban  populations or those near industrial areas of highways with heavy
 vehicular traffic.

 9.3.2.4  Quantitative Risk Analysis

     The most quantitative and precise estimation  of risk can be obtained
 by  use  of human health data from epidemiologic studies.   This is often net
 possible because of the lack of quantified exposure data, the uncertainty
 in  or lack of human effects data, or the confounding influence of a
 number  of other variables affecting exposure and/or health effects.

     Because of the lack of human health effects data for many chemicals,
 the availability of data for laboratory animals, and the continued desire
 to set specific levels of ambient concentrations of pollutants for the
protection of human health, a great deal of emphasis has been placed in
                                  9-11

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                      TABLE 9-].   EXAMPLE OF RISK  CONSIDERATIONS  BY  USE OF MARGINS OF SAFETY—PENTACHLOROPHENOL
 I
M
l-o
                     Exposure  SituatIon/Pathway

                  Max 1 muin  Ex posmrti
                  Food
                  Drinking Water
                  Inhalation -  Ambient
                  Dermal - Home Use - Spill
                     TOTAL
Exposure of Typical Person
Food
Drinking Water
1 "ilia 1 u t j oil Amii 1 en t
Dermal
   TOTAL
                 Exposure of Person Living
                 Near Cooling Tower
                 Food
                 Drinking Water
                 Inhalation
                 Dermal
                    TOTAL
Exposure
(mg/day)
24
0.024
0.003
170
194.0
1.5
0.00002
0.003
0.003
1.5
1.5
0.00002
2
0.003
3.5

(mg/kg/day)
0.4
0.0004
2.8
3.2
0.025
_
_
0.025
0.025
0.03
0.55
Estimated
Margin of
Safety
15
15000
20
2.14
1.7
240


240
240
200
109
                Ratio of  lowest  reported no effect level (6 mg/kg for fetotoxicity)  to exposure  level.

                It  is not known  how  "typical" these exposures are; the levels in drinking water  are  known  to  he  low
                and numerous  locations have been sampled.  No monitoring data are available  for  air.  Limited data
                are available  for  food, and the detection of PCP was not widespread.

               Source:  Adapted  from Scow, K. et al.  An exposure and risk assessment for pentachlorophenol    Final
                        Draft  Report.  Contract EPA 68-01-3857.  Washington, DC:  Monitoring and Data Support Division
                        Office of  Water Planning and Standards, U.S. Environmental Protection Agency; 1980.

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        TABLE 9-2.  EXAMPLE OF ADVERSE EFFECTS SUMMARY-
                    ADVERSE EFFECTS OF LEAD ON MAN
 Adverse Effect


 Carcinogenesis

 Mutagenesis

 Impaired Spermatogenesis

 Fetotoxicity

 Encephalopathy



 Noticeable Brain
   Dysfunction

 Peripheral Neuropathy

 Nephropathy


 Reversible

 Anemia
 Elevated free  erythrocyte
 protoporphyrin
Lowest Reported Effect
	Level	
  (US Pb/100 ml)
         50

       30-40

     80—children
    100—adults

    50-60—children


       50-60

    40—children

    50—adults



    50-60—adults
    15-20—children
    and women
 Urinary  5-aminolevulinic
 acid
 5-aminolevulinate de'nydratase
    25-30—men

         40
No-detected-effeet-Level
     (ug Pb/100 ml)'

 > 40 occupational

 40-120 occupational

          23-41



    60—children
  > SO—adults
                   i
    50—children


          40
         10
    40—children
    50—adults

    20—children and
    women

    25—men.

      <  40

      <  10
Source:   Perwak,  J.  £t a^.   An  exposure  and  risk assessment for lead.
         Final Draft Report.  Contracts  EPA  68-01-3857 and 68-01-5949.
         Washington, DC:  Monitoring  and Data Support Division, Office of
         Water Regulations  and  Standards, U.S. Environmental Protection
         Agency;  1982a.
                                  9-13

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               TABLE 9-3.
EXAMPLE OF EPIDEMIOLOGICAL EVIDENCE OF
HUMAN EXPOSURE—LEAD BLOOD LEVELS IN MAN
 Location.
 Adults

 Rural/Urban
 Urban
 Rural
Within  3.7 meters of
Highway

Living  Near a  Smelter
Children
Urban  (primarily)
Within 30 meters of
Highway

Near Smelter—Kellogg,
ID—1974 (immediate
vicinity)
1975
1979
El Paso, TX
                              Blood  Level
                              (ug/ 100  ml)
    9-24

  Most ^
    Reference-




 Bell _ec_ al.  (1979)



 Tepper and Levin  (1972)
  18 — mean (adjusted
  for age and smoking)

  Less than 57, > 30

  16 — mean (adjusted
  for age: and smoking)

  Less than 0.5% > 30

  23 — mean              Daines et al.  (1972)
    167,  >40
  40,000  children de-
  tected  annually
  >   30

 "" 20 yearly  geo-
 metric  :nean

 507, > 40
 99% > 40
 60% > 60

 Somewha:: reduced'
 Almost all < 60f
 and raosc < 40

 70% > 40

 14% > 60
                                                   Landrig:an  e_c_ al.  (1975)
                                                   Billick et_ al.  (1980)
                        Caprio et_ al. (1974)
Walter e_t_ al.  (1980)
Anonymous  (1979)
                                                   Landrigan e_t_ al. (1975)
 Reduction as a result of reduced atmospheric  emissions  as  we'l as
 increased sanitary procedures for r:he workers who  were  apoarently
 exposing their children  to  lead  through  their clothing.
 *See source indicated  below  for  references.
 Source:  Perwak, J. et_ al_.  An exposure and risk assessment for lead.
          Final Draft Report.  Contracts EPA 68-01-3857 and 68-01-5949.
          Washington, DC:  Monitoring and  Data Support Division, Office
          of Water Regulations and Standards, U.S.  Environmental Protec-
          tion Agency;  1982a.

-------
 recent years on extrapolating laboratory animal test data to estimate
 health effects in humans and assigning environmental criteria or standards
 based upon this quantitative approach.  As mentioned earlier, there has
 been a great deal of controversy over the type of laboratory animal data
 that should be considered,  methods of extrapolation, the validity of the
 results,  and the use of these extrapolation procedures for the develop-
 ment of regulatory standards.  A complete discussion of these issues is
 beyond the scope of this risk analysis methodology document.  However,
 since this type of quantitative analysis can be conducted where data are
 available, it deserves  some discussion,  if only to indicate how the
 methods can be used,  and to stress precautions in their use.  (Mathematical
 details of the application  of the methods are discussed in Appendix A.)


      The  toxicity of  a  substance  in a  particular  species  can often  be
 expressed in  terms  of a dose-response  curve, which quantifies  the like-
 lihood  or degree  of a specific  harmful effect  occurring at  various  dose
 levels.   In  some  cases,  acute toxic doses  for  humans  may  have  been  iden-
 tified.   However,  in  order  to obtain  the  dose-response  relationships  for
 sub-acute or  chronic  effects  in humans,  controlled laboratory  experiments
 must  be performed with  a species  of laboratory  animal  presumably having
 similar sensitivity to  the  substance.  When  data  in  humans  are  lacking,
 acute effects  data  for  laboratory animals  are  generally easy to obtain.
 However,  evaluation of  chronic  exposure  at  low-dose  levels,  corresponding
 to typical ambient concentrations  of pollutants in the  environment,  re-
 quires  an enormous number of  experimental  animals  to  demonstrate a  statis-
 tically meaningful response  frequency.   Instead,  a practice  has evolved to
 perform such  experiments  with a moderate number of animals  at high  dose
 levels  (maximum  tolerated dose),  and then  to extrapolate  the  results of
 lower doses.   The extrapolation procedure  raises  a number of questions.


      One  point of controversy is  the existence of  a  threshold  for carcino-
 genic and mutagenic response  to a  pollutant.  Some argue  that an organism
 is able to cope with  low  doses  of  a substance through metabolic processes
 or repair mechanisms, so  that harmful  effects do not appear until a
 certain minimum  threshold ,  or  "safe dose," has been surpassed.  There
 is evidence to suggest  that for many types of chemicals different meta-
 bolic processes occur at  high dose levels than at  low dose levels, and
 this  raises questions about the validity of linear extrapolation models.
 Others  contend that a toxic substance must be considered potentially
harmful at any dose and that a "zero tolerance" level should be assumed.
This issue has often been circumvented by the approach of selecting an
 "acceptable" risk level and  determining the corresponding acceptable
dose.   From a practical point of view, the behavior of the dose-response
curve at  low doses may be  an academic question, since there is unavoid-
able background response due to a multitude of naturally occurring toxic
agents, as well as the genetic heterogeneity of human populations!  Hence,
for a specific substance the real issue is whether the human response to
the substance significantly  emerges from this general background "noise."
                                  9-15

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     Another important issue is the applicability to humans of experi-
mental data on animals.  The derivation of a human dose-response curve
from animal data is predicated on the assumption that a substance with
demonstrated toxicity in certain laboratory animals has a probable
analogous effect on man.   However,  the toxic effects of many substances
appear to be species dependent, as a result of different metabolic patterns
Toxic effects of a chemical may differ even among strains of the same
species,_or; for different sexes and ages.   Ideally, the toxicity for man
 should be verified through epidemiologic studies in situations where
the substance was known to be present.  Even if the substance is indeed
toxic to man, the issue remains of how to estimate the relative potency
of the substance in man as compared with animals.  The common practice
is to use body weight or some power thereof to normalize the dose levels
between  different species.  However, there remain the questions of the
similarity of metabolism, bioaccumulation, and excretion of the pollutant
and its pharmacokinetics within the laboratory animal and man.  One must
also reconcile the life span of the animal and its stages of development
relative to those of man.

     Finally, the issue arises of what shape to ascribe to the dose-
response curve, when extrapolating from high to low doses.   The simplest
assumption that can be made is that the dose-response relationship is
linear throughout the entire dose range.  This follows from the so-called
"one-hit" hypothesis, which holds that each molecule of the substance
contributes equally to the likelihood of toxic effect, and hence that
there is no threshold.  A rival hypothesis is offered by the Mantel-Bryan
method, which uses an S-shaped dose-response curve that generally yields
a much lower risk when extrapolated to low aoses.  Other methods that
consider multi-hit or multi-stage response, time to response, and repair
mechanisms have also been discussed in the literature. (These methods are
described in the Appendix.)  In practice,  the linear "one-hit" model is
the easiest to apply, although it tends to give conservative results,
which may overestimate toxicity.   At present none of these models has
been verified for specific health effects, and the use of any of them is
still controversial.   For extrapolation of cancer risks,  the multi-stage
models appear to agree best with  known biological phenomena and are
presently recommended bl  the EPA.

     If these models are  used in  the attempt to quantify  the relationship
between animal and human  effects  and effects levels,  explicit mention
should be made of the assumptions  in the process.   These  might include:

     •  Comparative susceptibility  of humans and experimental animals.

     •  Interpretation of observed  effects in animals.

     •  Method of dose administration.

     •  Computational procedure  for dose conversion.

     •  Model selected for extrapolation co low doses.
                                    9-IS

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 Given the present state of  the art, the uncertainty associated with such
 assumptions cannot be quantified, except perhaps by subjective evaluation.
 However, it is possible to  derive, in some cases, statistical confidence
 bounds on the dose-response estimates, based upon the size of the experi-
 ment and the number of responses.  Thus, at least a part of the overall
 uncertainty may be expressed numerically.

      When it is possible to attempt a quantitative analysis of health
 effects  by extrapolating from laboratory animals to humans, the approach
 may be summarized as follows.   From a careful review of the laboratory
 animal studies,  the one or ones are selected that most closely represent
 the human health effects considered in terms of animal species,  dose
 levels,  exposure routes,  biological and metabolic processes,  confidence
 of data,  and other variables and  assumptions made earlier.   Wherever
 possible,  a  variety of  models—one-hit, log-probit,  multi-hit,  etc.—
 should be used  to extrapolate  from the  high  doses of the animal  experi-
 ments to  the low doses  of  the  anticipated  exposure levels for  the  general
 and specific human population  groups.   Using these methods,  one  can  then
 estimate  the range of risks  to  humans  associated with  exposure  to  environ-
 mental concentrations,  using confidence levels  if  possible.

      A quantitative  analysis of the  carcinogenic risks  of 1,2-dichloro-
 ethane exemplifies  this  approach  (Perwak _et_  al.  1982b).   No  data were
 found directly  relating  doses of  1,2-dichloroethane  to  responses in
 humans.   Because  of  apparent species specificity of  responses and  incon-
 clusiveness  of  the  results,  studies  of  mutagenicity  and'many other toxic
 effects in laboratory animals could  not be extrapolated  to  humans.   The
 data selected for extrapolation were the NCI data  that  demonstrated  in-
 creased alveolar/bronchial adenomas  in  male  mice and increased mammary
 adenocarcinomas  in female rats  (NCI  1978).   These  data  are  listed  in "
 Table 9-4.   Other  types of carcinomas were observed  in both  species  such
 as  hemangiosarcoma,  but  the  implied  dose-response  relationships were not
 as  severe.

      The experimental results in  Table'9-4 for both mice  and rats show
 three animal groups:  the vehicle controls (zero dose),  the low-dose
 group, and the high-dose group.   In both species the low-dose results
were  not statistically significant, so  that  the high-dose results alon-
were  used for extrapolation  to humans.  The  first step in this extrapola-
 tion  was to calculate the equivalent human dose rate corresponding to  the
experimental treatment.   The approach recommended by the EPA was followed
which accounts for the duration of exposure relative to the animal life- '
span  and normalizes the dose rate according to body surface area (U.S.
EPA^1979d).  This approach is conservative, in that it results in a'lower
equivalent human dose than would be obtained  from simple multiplication
of animal dose rate (mg/kg/day)  by human body weight.

 _    Whether  surface area or body  weight is a more appropriate normaliza-
tion factor is still open to debate.   The former method yields  a dose
rate about 6  times lower for rats, and  about  14  times lower for m^'ce    Thus
                                                                           '

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             TABLE 9-4.  EXAMPLE OK CARCINOGENICITY DATA USED FOR RISK EXTRAPOLATION OF 1,2-DICHLOROETHANE
I
M
00
Species
Tested

Male mice

Average
Body
Weight
(kg)
0.025

Time-Weighted
Average Dose
(mg/kg/day)
195

Observed
Response
(%)
15/48 (31%)

Observed
- Effects

alveolar/
bronchial
adenomas
Duration of
Exposure
(week)
78

Animal
Life span
(week)
90

        Female rats
        0.32
                                       97
                                        0
                                    1/47  (2%)
                                  (vehicle controls)0/20
95
                                       47
18/50 (36%)
                                    1/50 (2%)
                           mammary

                           adeno«-

                           cinomas
78
110
                                  (vehicle controls)0/20
       Source:
Perwak, J. et a_l.  An exposure and  risk  assessment  for  dichloroethanes.   Final  Draft  Report.

Contracts EPA 68-01-5949 and  68-01-6017.   Washington, DC:  Monitoring  and Data  Support  Div.,

Office, of Water Regulations and Standards,  U.S.  Environmental  Protection  Agency;  1982.

-------
      The actual calculation of equivalent human dose was performed as
 follows, assuming an average human weight of 70 kg:

                                                   !_          duration of
 Human dose = 70 kg X animal dose X (anim*l weight 3 x (5.}   (exposure	
                                     human weight       7     animal     '
                                                              lifespan


      The correction factor for body surface area is the cube root of the
 ratio of animal to human weight,  as shown by the U.S. EPA (1979d) .   A
 correction factor of 5/7 was also included since the animals were treated
 only on five days per week.  As a result, it was concluded that:

      «  the dose of 195 mg/kg/day,  which produced a 31% effect in male
         mice, was equivalent to a human dose of approximately 600 mg/day;
         and

      •  the dose of 95  mg/kg/day, which produced a 36% effect in female
         rats, was equivalent to a human dose of approximately 560 mg/day.

 These results are roughly the same, with slightly greater potency implied
 by the rat  experiment.   Therefore,  only the  rat data were used in subse-
 quent risk  estimation.

      Three  separate extrapolation models were  applied—the  linear,log-probit
 and multi-stage models (see the  appendix)  using  the data for  female  rats
 (i.e.,  36%  response at  a human  equivalent of 560  mg/day).  The "one-hit"
 extrapolation is  performed by simply assuming a constant  increase in
 probability of  tumor induction  for each increment  of  dose.   This leads
 to a gradually  rising dose-response curve, which  is nearly linear at
 sufficiently  low  doses.   The  log-probit model assumes  that carcinogenic
 doses  are log-normally  distributed, resulting in an S-shaped dose-response
 curve  with  a  threshold-like  effect.  These two  models, generally speak-
 ing,  tend to  bound  the  range of risk estimates  that could be obtained
 from other  dose-response  models.  The one-hit model is conservative, in
 that it probably  over-estimates the true  response  at  low doses,  whereas
 the  log-probit model usually results in much  lower risk estimates for
 typical human exposure  levels.  The multi-stage model was applied to the
 combined rat and mouse data.  The multi-stage model generally *ives dose-
 response estimates intermediate to the on-hit and  log-probit'models.

     It must be noted that interpretation of the results from these  three
 extrapolation models for assessment of human risk due to exposure to
 1,2-dichloroethane is subject to a number of important qualifications and
assumptions:
                                   9-19

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     •  Although positive carcinogenic findings exist, there have been
        contradictory negative findings in tests with the same species
        using different routes of exposure.  No adequate explanation has
        been found for these disparate results.

     •  Assuming that the positive findings indeed provide a basis for
        extrapolation to humans, the estimation of equivalent human
        doses involves considerable uncertainty.

     •  Occurrences of human exposure to 1,2-dichloroethane are assumed
        to be numerous.

     »  The effect on rodents of chronic exposure at: low doses, such as
        those possibly encountered in human exposure, may be deduced by
        extrapolating from higher gavage doses used in the NCI experiments.

     o  Due to inadequate understanding of the mechanisms of carcinogenesis ,
        there is no scientific basis for selecting among several alternate
        dose-response models, which yield differing results.

     In Table 9-5 the estimated risks of exposure to 1,2-dichloroethane
obtained from these models are summarized.  The expected number of cancers
per million exposed population is shown for daily exposures to 1,2,-
dichloroethane ranging from 1 ug to 1 mg.  The gap between the estimates
is large in the low-dose region; only at doses above 10  ug/day does the
log-probit dose/response curve begin to rise more steeply.  The dose
corresponding to a per capita risk of 10~- is about 100  yg/day according
to the log-probit model, which is about eight times greater than the
level obtained from the linear model.  The multi-stage model predicts
a risk intermediate between these two levels in the range of 1 ug/day to
100 ug/day.

     In Table 9-6  the results from the three extrapolation models are
applied to estimated average lifetime exposure of the general population
and several subpopulations to 1,2-dichloroethane via ingestion and in-
halation.  As shown, the subpopulation drinking highly contaminated ground-
water appears to be the group at highest possible risk due to waterborne
exposure.  Because of limited monitoring of levels in groundwater, the
size of this subpopulation cannot be estimated reliably.  Other uncertain-
ties result from the availability of only limited data on residues in
spices and other foods and on atmospheric concentrations in urban areas.

     Thus there is a substantial range of uncertainty concerning the
actual exposure levels and carcinogenic effects of 1,2-dichloroethane.
However, present scientific methods and limited data availability do
not permit a more definitive assessment of risk to humans resulting
from environmental exposure to this compound.

9.3.3  Evaluation of Risk for Aquatic Species

     Although much of the focus of the risk considerations section of an
overall risk assessment is devoted to evaluating human health risks,
risks to fish, other aquatic species, and wildlife should also be con-


                                 9-20

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   TABLE  9-5.   EXAMPLE OF ESTIMATION OF UNIT CARCINOGENIC RISK:   ESTIMATED
               NUMBER OF EXCESS  LIFETIME CANCERS  PER 1,000,000 POPULATION
               EXPOSED TO DIFFERENT LEVELS  OF 1,2-DICHLOROETHANE
                              Niamber of Excess Lifetime  Cancers  Per  10°
 Extrapolation Method         	Population  at Exposure Level*
                              1 ug/day   10 ug/day  100  yg/day   1000  ^g/day


 One-hit  extrapolation          0.8           8          80           800


 Log-probit extrapolation     negligible      0.1        13           690


 Multi-stage model               0.5           5        '50          500


 Carcinogen Assessment Group     Q.5            5          50          son
 Estimated excess lifetime cancers are given based on three different
 dose-response extrapolation models.  The lifetime excess incidence
 per 1,000,000 population exposed represents the increase over the
 normal background incidence, assuming that an individual is con-
 tinuously exposed to 1,2-dichloroethane at the indicated daily intake
 over their lifetime.  There is considerable variation in the estimated
 risk due to uncertainty introduced by the use of laboratory animal
 data, by the conversion to equivalent human dosage,  and by the appli-
 cation of hypothetical dose-response curves.   In view of several
 conservative assumptions that were utilized,  it is likely that these
 predictions overestimate the actual risk to humans.

Source:   Perwak,  J.,  et al.   An exposure and risk assessment for
         dichloroethanes.   Final Draft Report.   Contracts EPA
         68-01-5949  and 68-01-6017.   Washington,  DC:   Monitoring and
         Data Support Division,  Office of Water Regulations  and
         Standards,  U.S.  Environmental Protection Agency;  3982.
                                 9-21

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TABLE 9-6.  EXAMPLE OF ESTIMATION OF CARCINOGENIC RISK DUE TO
            ENVIRONMENTAL EXPOSURES:  ESTIMATED RANGES OF CARCINO-
            GENIC RISK TO HUMANS DUE TO 1,2-DICHLOROETHANE EXPOSURE
            FOR VARIOUS ROUTES OF EXPOSURE
          Route
Drinking water

Food

Inhalation
    Estimated
Average Lifetime
Exposure- (ug/day)
                     NO.  Excess
              Estimated Lifetime  Cancers
               (per million exposed)*3
<2

-5
                   One hit

                     1.6

                     4
                                                         Probit
 CAG

  1

  3
   rural                        <0.4
   urban                        <0.8
   industrial                  32-120
   in the vicinity of
      production facilities   0.8-80

Isolated subpopulations

   groundwater (maximum)        800
   inhalation in industrial    1300
     area
               0.3
               0.6
             30-100

             0.6-60
              600
             1000
                                 1-20

                             < 0.1-10
                                 500
                                1000
  0.2
  0.4
 20-60

0.4-40
  400
  700
 uata taken from Table 7-3 of the source cited below.

 Estimated excess lifetime  cancers  are given based on three different
 dose-response  extrapolation models.   The  lifetime excess incidence of
 cancer represents the increase over  the normal  background incidence
 assuming  that  an individual is continuously exposed to 1,2-dichloro-
 ethane at the  indicated  daily  intake over their lifetime.  There is
 considerable variation in  the  estimated risk due to uncertainty
 introduced by  the use of laboratory  rodent  data, by the conversion
 to  equivalent  human dosage,  and by the application of  hypothetical
 dose-response  curves.   In view of  several conservative assumptions
 that were utilized, it is  likely that these predictions over-  :a
 estimate  the  actual risk to humans.


 Source:   Perwak,  J., et  al.  An exposure and risk assessment  for
          dichloroethanes.  Final Draft Report.   Contracts EPA 68-01-
          5949  and  68-01-6017.  Washington, DC:  Monitoring and Data
          Support  Division,  Office of Water Regulations  and Standards,
          U.S.  Environmental Protection Agency; 1982.
                              9-22

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  sidered.  In general, qualitative approaches seem to be more practicable
  than quantitative approaches.  This is a consequence of the large number
  of species that might be considered, and the general lack of detailed
  exposure data for these individual species.  Case studies or exposure
  scenarios seem to be a useful approach for characterizing the range of
  risks.

      The first step in the evaluation of risk to aquatic species is to
 summarize information available on the exposure of different species,
 the locations of that exposure, and the environmental conditions that
 affect exposure.  Some of this information may be general, in the sense
 that actual exposure of fish and wildlife to observed concentrations of
 pollutants may or may not occur; however, the situations may be described
 as potential exposure conditions, where it is known that both the en-
 vironmental concentrations exist in the water, and fish and/or other
 aquatic species are known or suspected to inhabit the area in which these
 concentrations are found.   Environmental conditions that affect exposure
 include factors such as rainfall, hardness of water,  pH, seasonality of
 pollutant concentrations,  salinity, etc.

      The second step is to summarize data on fish and wildlife effects
 in terms of the most sensitive species,  types of effects observed,  LC  's,
 and/or other indicators of toxic effects,  and parameters that may in-50
 fluence toxic effects (e.g.,  other pollutants, water  hardness).   As  was
 the case in the human effects analysis,  it should be  possible to summarize
 no-effect level data for different species,  or lowest reported effects
 data,  as well as more commonly available  values  such  as  LCcn's.   In  both
 the exposure and effects summaries,  ranges  of values  for exposure and
 effects  should be presented,  if available,  as well  as  the relative degree
 of  confidence in the data.

     The next step  requires a qualitative  comparison  of  the exposure and
 effects  data.   From this comparison, one  can  determine the species and
 locations in which  significant  adverse effects might  be  expected  to  occur.
 For example,  if  it were established  that  the  LC-  's for  a particular
 species  had  values  that were  in the  same range as environmental  concen-
 trations  of  pollutant  in a particular location, and it were expected  that
 species  might  inhabit  that location, then there would be a possibility
 of  significant risk  to  that species in that location.  Thus the analysis
 becomes  one  of establishing the  "key intersections" between exposure
 and effects  data with  regard  to specific species and geographic locations.
 In  this  regard,  risk considerations for fish and wildlife often tend to
 be  more  specific with  respect to geographic locations than do risk
 considerations for human health.

     The end result of this process can be a listing or summary of
 species, locations, exposures, and effects levels, which indicate the
 combinations most likely to result in high risks.  In some cases, it is
 possible to attempt some quantitative comparisons, i.e.,  to determine"
 the extent of a specific health effect on fish and wildlife by utilizing
 values such as LC5Q's and concentrations in the ambient water.  As ex-
 plained in the section on aquatic effects,  caution must be exercised  in
 developing these mathematical  relationships because of the differences'
between results under laboratory conditions and fiald  conditions.   For
 this reason,  it is important to identify those environmental  factors  or
 conditions that can influence  the adverse  effects.

                                    9-23

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      In order to develop the risk analyses further,  case studies of in-
 dividual exposure/effects situations  can be investigated.   For example,
 one can pick several of the  "key intersections" of exposure and effects
 data and determine through field interviews,  discussions with local
 experts, examination of evidence of  fishkills,  or  actual field sampling
 programs,  whether there is real  evidence of exposure and/or damage to
 the fish or wildlife population.   Specific sources located in or near
 the area can be investigated,  appropriate mathematical  models of pollu-
 tant dispersion can be  used  to estimate  concentrations  of  the pollutant
 in  the water and comparisons with ambient monitoring data  can be made
 in  order to help define the  potential  risk for  those sensitive species
 that inhabit the area.   Environmental  factors should be considered that
 could affect toxicity and are  specific to these  geographic areas.   The
 main purpose of these case studies is  to  confirm the existence of sig-
 nificant risk to fish or wildlife species in areas in which exposure
 can occur  and effects are anticipated.   The number of case studies con-
 ducted depends  upon the scope  of  the risk analysis and  the numbers and
 types of locations  in which  exposure is  expected to  occur, and the nature
 and magnitude of the  potential adverse effects.

      An example of  the  information that  can be  obtained  in the case study
 approach is given below.   Analysis of  the aquatic  risks  associated with
 copper in  the environment, showed that LCso's for  a  number of sensitive
 species were below  100 ug/1  in the laboratory (Perwak e_t al.  1980).   River
 basin summaries  (STORET)  revealed that the  mean  levels  of  copper  reach  or
 exceed this level in  numerous  locations  in  the U.S.  and  this  suggests
 that  the potential  risk to fish and invertebrates  is  widespread.   Further
 examination of  detailed  data from individual monitoring  stations  in
 several of  these river  basins  indicated  that the mean concentrations were
 not representative  of ambient conditions, but resulted  from very  elevated
 concentrations  in a few locations.  Consideration of  the form of  copper
 involved,  factors favoring complexation and adsorption, and actual  reports
 of  fish kills indicated  that risk exists  to organisms in specific  loca-
 tions,  but  that  the risk is neither as severe nor as widespread as would
 have  been predicted from laboratory data.

      The end  result of risk considerations for fish and wildlife will
 generally be a series of summary  statements indicating the locations in
which  adverse effects are likely   to occur, the species that are likely
 to be  affected,  the environmental conditions that influence whether or
not the potential effects actually occur, and the results of case
studies  to confirm or establish the magnitude of the potential problems.
In addition, areas for further investigation should 'be identified.

 9.3.4   Summary of Risk Considerations

     The approaches described above can provide  specific information on
the nature and extent of the risks to both general  and specific human
subpopulations and to fish and other  aquatic biota.  Depending upon
the type and level of data available  concerning  exposure and effects,
                                  9-24

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specific conclusions may be drawn giving the ranges of risks and the
degree of precision associated with these risks.  In some cases, only
qualitative aspects of risks can be presented; in others, quantitative
information may be appropriate.

     In either case, the overall risk posed by the pollutant should be
portrayed so that regulators and the public can visualize whether or not
significant problems are expected to occur.  A number of methods of pre-
senting this overall summary of risks are possible:  tables or charts
showing specific risks to humans and other species, charts or graphs
showing the relative risk associated with different effects, etc.  An
approach that has the potential for effectively summarizing the results
of risk considerations is to prepare a graphic presentation of exposure
and effects in terms of the same variable and to indicate the areas in
which the combinations of exposure situations and effects levels can
present significant risk.  This approach could be followed for both human
health effects and effects on fish and aquatic species and could be
specific to a particular type of effect, type of exposure, or other
characteristics.

     One method of presentation is to plot the relative  frequency of
exposure in terms of concentration or average daily intake, the frequency
being defined in general terms such as "usual," "frequently," "occasional,
"rare exposure."  On the same graph, one could plot the  likelihood of
various toxic effects at levels such as LC5Q for various species.  The
intersection of the exposure and effects curves, or more precisely the
area bounded by the intersection, would indicate the areas of significant
potential risk.

     As an example of this type of presentation, Figure  9-3 shows a dia-
grammatic plot of the relative frequencies (ordinate) of both aquatic
exposure levels and reported effects levels in terms of  the surface
water concentrations of arsenic (abscissa) (Scow _e_t al.  1982). -Surface
water concentrations of 1 mg/1 are rarely observed.  The shading indi-
cates the approximate degree of uncertainty associated with the data
points used.  The area under the intersection of the curves represents
the region of potential risk where the observed water concentrations have
values that exceed reported adverse effects levels.

     Though such a plot of exposure and effects frequencies can be a
useful conceptual tool, its interpretation must be made  in light of the
representativeness of the monitoring data base, the validity of gener-
alizing from the available toxicological data (number of species tested,
chronic versus acute effects), and other factors such as bioavailability.

     If sufficient data are available concerning effects and exposure
levels for humans, a similar plot could be used to summarize the like-
lihood of significant potential risk.
                                   9-25

-------
                                Possibility
                               of Occurrence
>£>
I
                           Usual
                           Frequent
                          Occasional
                          Rare
                                               Aquatic
                                               Exposure
                                               Levels
Adverse
Effects
Levels
                                        0.0001   0.001
                    Concentration
                        Surfac
                       Water
                                                                                     (mg/l)
                               0.01   f    0.1    f    1.0       10      100
                                   Lowest    Freshwater
                                  Reported   Criterion for
                                 Acute Effects  Protection
                                    Level   of Aquatic Life

FIGURE  9-2   EXAMPLE OF RISK CONSIDERATIONS  SUMMARY FOR  AQUATIC BIOTA—ARSENIC  EXPOSURE
             AND TOXICITY TO AQUATIC ORGANISMS

Source:   Scow,  K. , e± a±.   An exposure  and  risk assessment for arsenic.   Final  Draft Report,
          Contract 68-01- 6160, 6017.  Washington DC:  Monitoring and  Data Support  Division,
          Office of Water Regulations and  Standards,  U.S.  Environmental Protection Agency,
          1982.

-------
                               REFERENCES
 Albert,  R.E.;  Train,  R.E.;  Anderson,  E.   Rationale  developed  by  the
 Environmental  Protection Agency  for  the  assessment  of  carcinogenic risk.
 J.  Nat.  Cancer Inst.  58:1537-1544; 1977.

 Cornfield,  J.   Carcinogenic risk assessment.   Science  198:693-699; 1977.

 Gori,  G.B.   The regulation  of  carcinogenic hazards.  Science  208:256-
 261;  1980.

 Kensler,  C.J.   Experimental procedures in the  evaluation of chemical
 carcinogens.   Coulston,  F.  ed.   Regulatory aspects  of  carcinogens and
 food  additives:  The  Delaney Clause.  New York, N.Y.:  Academic  Press;
 1979:  239-260.

 National  Academy of Sciences (NAS).   Drinking  water and health.
 Washington,  DC:  National Academy of  Sciences; 1977.

 National  Cancer  Institute (NCI).  Bioassay of  1,2-dichloroethane for
 possible  carcinogenicity.   Tech. Report NCI-CG-TR-44.  Washington, DC:
 National  Cancer  Institute;  1978.

 Perwak, J.;  Bysshe, S.;  Delos, C.; Goyer, M.;  Nelken, L.; Schimke, G.;
 Scow,  K.; Walker, P.; Wallace, D.  An exposure and risk assessment for
 copper.   Final Draft  Report.  Contract EPA 68-01-3857.  Washington, DC:
 Monitoring and Data Support  Division, Office of Water Planning and
 Standards, U.S.  Environmental Protection  Agency; 1980.

 Perwak, J.;  Goyer, M.; Nelken,  L.; Payne, E.;  Scow, K.; Wallace, D.;
 Wood,  M.  An exposure and risk assessment for  lead.  Final Draft Report.
 Contracts EPA 68-01-3857, 68-01-5949.  Washington, DC:  Monitoring and
 Data Support Division, Office of Water Planning and Standards, U.S.
 Environmental Protection Agency;  1982a.

 Perwak, J. ; Byrne, M.; Goyer, M.  ; Lyman,  W,. ; Nelken, L. ;  Scow, K. ;
 Wood, M.; Moss, K.  An exposure and risk assessment for dichloroethanes.
 Final Draft Report.  Contracts  EPA 68-01-5949, 68-01-6017.   Washington,
 DC:  Monitoring and Data Support  Division, Office of Water Regulations
 and Standards,  U.S. Environmental Protection Agency; 1982b.

 Peto, R.   Distorting the epidemiology of  cancer:   the  need  for a more
 balanced overview.  Nature 284:297-300;  1980.

 Scow, K.; Gilbert, D.; Goyer, M.; Perwak, J.;  Payne, E.;  Thomas,  R.;
Walker, P.; Wallace,  D.; Wechsler, A.; Wood,  M.';  Woodruff,  C.   An
 exposure  and risk assessment for  pentachlorophenol.   Final  Draft  Report.
Contract  EPA 68-01-3857.  Washington,  DC:  Monitoring  and Data Support
Division, Office of Water Planning and Standards,  U.S.  Environmental
Protection Agency;  1980.


                                 9-27

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U.S. Environmental Protection Agency (U S  EPA}   Tni-^-
                                     water
connnents on report.   Federal Register 44:39858-3987   197%
                                                is.™ ••
                             9-28

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             10.   BIBLIOGRAPHY OF REFERENCE MATERIALS FOR
                   USE IN EXPOSURE AND RISK ASSESSMENTS
10.1  INTRODUCTION

     The following bibliography is intended to provide an initial means
of identifying reference materials for use in conducting exposure and
risk assessments for environmental pollutants.  The bibliography is
organized according to the following six topical areas of investigation:

     •  Materials Balance

     •  Environmental Pathways and Fate

     •  Monitoring Data and Environmental Distribution

     •  Human Exposure and Effects

     •  Exposure and Effects—Non-Human Biota

     •  Risk Estimation
                                  10-1

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10.2  MATERIALS BALANCE

      Abstracts and Searches

           Applied Science and Technology Index
           Bibliographies from U.S. Bureau of Mines
           Chemical Abstracts
           Engineering Index
           Environmental Abstracts
           Metals Abstracts
           NTISearch
           Pollution Abstracts

      Industry and Consumer Associations

           American Chemical Society
           American Institute of  Chemical Engineers
           American Institute of  Industrial  Engineers
           American Institute of  Mining,  Metallurgical  and  Petroleum
              Engineers
           American Iron and Steel Institute
           American Paper Institute
           American Petroleum Institute
           American Public  Works  Association
           American Society of  Sanitary Engineers
           Association of Home  Appliance  Manufacturers
           Chemical Manufacturers  Association
           Environmental Defense  Fund
           Environmental  Information Center
           Gas Appliance Manufacturers Association
           Glass Packing Institute
           National Agricultural Chemicals Association
           National Ash Association
           National Association of Recycling Industries
           National  Family  Option
           National Association of Manufacturers
           National Lime Association
           National Solid Waste Management Association
           Natural Resources Defense Council
           Society of Manufacturing Engineers
           Society of Mining Engineers
           Society of Plastic Engineers
           Synthetic Organic Chemicals Manufacturers Association
          The Fertilizer Institute
          Water and Wastewater Equipment Manufacturers Association
          Zinc Institute
                                  10-2

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Periodicals

     Agricultural Chemicals
     AIChE Journal
     American Dyestuff Reporter
     American Paint Journal
     American Paper Industry
     Automotibe Engineering
     Beverage Industry
     Chemical and Engineering News
     Chemical and Metallurgical Engineering
     Chemical and Petroleum Engineering
     Chemical Engineering (Chemical Engineering Equipment Buyers Guide)
     Chemical Engineering Progress
     Chemical Marketing Reporter
     Chemical Processing
     Chemical Week
     Chemtech
     Coal Age
     Coal Mining  and Processing
     Engineering  and Mining Journal
     Food Engineering
     Food Industry
     Industrial Wastes
     Journal  of the  American Water Works Association
     Journal  of the  Air Pollution  Control Association
     Journal  of the  Water Pollution Control Federation
     Machine  Design
     Mining Engineer
     Modern Packaging
     Modern Plastics
     Oil  and  Gas  Journal
     Packaging  Design
     Pit  and  Quarry
     Plant Engineering
     Plastics Engineering
     Plastics Technology
     Plastics World
     Process  Engineering
     Pulp and Paper
     Rubber Age
     Solid Waste Report
     Solid Wastes Management
     TAPPI
     Textile Worlds
     Water and  Sewage Works
     Water and Wastes Digest
     Water and Wastes Engineering
                            10-3

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Books
     Census of Manufacturers,  U.S.  Dept.  of Commerce,  Washington,  DC
     U.S. Geological Survey Yearbook, U.S.G.S.,  Washington,  DC
     Mineral Facts and Problems,  U.S. Bureau of  Mines, Washington, DC
     SME Mining Engineering Handbook, I.A.  Given (ed.), AIME,  NY
     Chemical Process Industry, R.  Shreve and J. Brink, McGraw-Hill,  NY
     Unit Operations of Chemical Engineering, W. McCabe and  J. Smith,
        McGraw-Hill, NY
     Metal Bulletin Handbook,  R.  Packard  (ed.),  Metal  Bulletin Ltd.,
        London
     Metal Statistics, P. Cere (ed.), Fairchild  Publications,  NY
     Minerals Yearbook, U.S. Depc.  of Interior,  Bureau of Mines,
        Washington, DC
     Mining Engineer's Handbook, R. Peele (ed.), John Wiley and Sons,
        NY
     Oil and Gas International Yearbook,  P. Jenkins (ed.), Business
        Enterprises, London
     Petroleum Processing Handbook, W.F.  Bland and R.L. Davidson
         (eds.), McGraw-Hill, NY
     Chemical Regulation Reporter, The Bureau of National Affairs,
        Washington, DC
     Chemical Engineering Practice, H.W.  Cremer and T. Davis  (eds.)
        Butterworths Scientific Publications, London
     Moody's  Industrial Manual, Moody's Investors Service, NY
     Encylcopedia  of Chemical Technology, R.E. Kirk and D.F. Ohmer,
         Interscience Encyclopedia, Indc.  NY
     The Encyclopedia  of Chemistry, C.A.  Hampel and G.G. Hawley
         (eds.), Van Nostrand Reinhold Co., NY
     Directory of  Chemical  Producers, U.S.A., Chemical Information
         Services,  Stanford  Research  Institute, Menlo  Park, CA
     Chemical Sources, U.S.A., Directories Publishing Co.,
         Fleming,  NJ
     Manufacturing Processes Dictionary, H.R. Clause:: (ed.)
         Technomic Publishing Co.,  Westport,  CN
     Industrial Product  Directory, Cahness Publications,  Stamford
     SOCMA Handbook, American  Chemical Society, NY
     Rare  Metals  Extraction by Chemical  Engineering Techniques,
         W.D.  Jamrock,  Pergamon,  NY
     Jane's World Mining,  Jane's Yearbooks,  London
     Mines Register,  New York
      Handbook of  Non-Ferrous Metallurgy, D.M. Liddele (ed.) McGraw-
         Hill, New York
      Clarke,  R.K., J.T.  Foley, W.F.  Hartman, D.W. Larson.   1976.
         Severities of Transportation Accidents,  Sandia Laboratories
         Report,  SLA-74-001.
      Annual Reviews,  U.S.  Air Carrier Accidents,  National Transporta-
         tion and  Safety Board, Bureau of Aviation Safety
      Preliminary  Analyses  of  Aircraft Accident  Data.   (Annual)  U.S.
         Civil Aviation NTS3 Reports-
                            10-4

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     Accidents of Large Motor Carriers of Property.  (Annual)
        Bureau of Motor Carrier Safety, Federal Highway Administra-
        tion, U.S. Department of Transportation
     Accident Bulletins and annual Summary and Analyses of Accidents
        on Railroads in the United States.  U.S. Department of
        Transportation, Federal Railroad Administration, Bureau of
        Railroad Safety
     AAR-RPI Railroad Tank Car Safety Research and Test Project.
        A series of Reports 1972-1976
     Solomon, K.A., M. Rubin, and D. Okrent, 1976.  On Risks from
        the Storage of Hazardous Chemicals, University of California,
        University of California, Los Angeles Report UCLA - ENG -
        76125, December 1976

Major EPA Studies

     Development Documents for Effluent Limitations Guidelines and
        Standards (by point source category).  Washington,  DC:
        Effluent Guidelines Division, Office of Water and Waste
        Management,  U.S.  Environmental Protection Agency
     Fate of Priority Pollutants in Publicly Owned Treatment Works.
        EPA-440/1-80-301.   Washington, DC:  Effluent Guidelines
        Division, Office  of Water and Waste Management,  U.S.
        Environmental Protection Agency;  1980.
     Water-Related Fate of 129 Priority Pollutants.  Volumes I and
        II.   EPA 440/4-79-029a,  b.   Washington,  DC:  Office of
        Water Planning and Standards, U.S. Environmental Protection
        Agency;  1979.
                          10-5

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10.3  FATE AND PATHWAYS ANALYSIS

      Periodicals

      Advances in Agronomy
      Advances in Applied Microbiology
      Advances in Chemistry Series
      American Chemical Society Symposium Series
      American Journal of Botany
      Analytical Chemistry
      Applied and Environmental Microbiology
      Archives of Environmental Contamination and Toxicology
      Atmospheric Environment
      Biochemistry
      Bulletin of Environmental Contamination and Toxicology
      Canadian Journal of Chemistry
      Canadian Journal of Microbiology
      Chenosphere
      Chemical Engineering News
      Endeavor
      Environmental Health and  Pollution Control
      Environmental Health Perspectives
      Environmental Pollution
      Environmental Science and  Technology
      Estuarine and Coastal Marine Science
      Journal Agricultural Food  Chemistry
      Journal of  Air Pollution Control Association
      Journal of  Association Off.  Anal.  Chem.
      Journal of  Environmental Quality
      Journal of  the American Chemical Society
      Journal of  Water Pollution Control Federation
      Marine  Chemistry
      Marine  Pollution Bulletin
      National Academy of  Science  (NAS)  documents
      Nature
      Pesticide Monitoring Journal
      Proceedings  of the American  Society of Horticultural  Science
      Proceedings  of the  Industrial Waste Conference  (Purdue University
        Engineering Bulletin)
      Proceedings  of the Royal Society of London
      Science
      Soil Biology  and  Biochemistry
      Soil Science
      Soil Science  Society American Proceedings
      The Science  of the Total Environment
      Water,  Air and Soil  Pollution
      Water Pollution  Abstracts
      Water Research
      Water Resource Bulletin
      Water Waste Treatment
      Weed Science
      World Health  Organization  (WHO)  documents
                                 10-6

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  Books, Articles, and Reports


 Altshuller, A. P.; Bellar, T.A.  Photochemical aspects of air pollution:
 a review.  Environ. Sci. Tech. 5.39; 1971.

 Callahan, M.A. ; Slimak, M.W. ; Gabel, N.W.; et_ al.  Water-related environ-
 mental fate of 129 priority pollutants.  EPA-44014-79-0292.  Washington,
 DC:  U.S. Environmental Protection Agency; 1979.

 Chion, C.T.; Peters, L.J.; Freed, V.H.  A physical concept of soil water
 equilibria for non-toxic compounds.  Science 206:831-832; 1972.

 Coniglio, W.A.; Miller, K. ; MacKeenen, D.  Briefing on the occurrence of
 volatile organics in drinking water.  Washington, DC:  U.S. Environmental
 Protection Agency; 1980.

 Cox, R.A.:  Derwent, R.G. ; Eggleton, A.E.J.;  Lovelick, J.E.  Photochemical
 oxidation of halocarbons in the troposphere.   Atmos.  Environ.  W -305-308 •
 1976.

 Billing, W.L.; Teferhiller, N.B.; Kallos, G.J.   Evaporation of methylene
 chloride, chloroform, 1,1,1-trichloroethane,  trichloroethylen, tetra-
 chloroethylene,  and other chlorinated compounds  in dilute' aqueous  solutions
 Sci. Technol.  9(9) :833-839 ; 1975.

 Fiksel, J.;  Bonazountas , M. ;  Ojha,  H.;  Scow,  K. ;  Freed,  R. ; Adkins,  L.
 An integrated  geographic approach to developing  toxic substance control
 strategies.   Final Draft Report.   Contracts EPA  68-01-6160  and 68-01-6271.
 Washington,  DC:   Office of Policy and Resource Management,  U.S.  Environ-
 mental Protection Agency;  1981.

 Jungclaus, G. ; Lopez-Avila; Hitres , R.H.   Organic compounds in an  industrial
 wastewater:  a case study of  environmental impact.  Environ. Sci.  Tech
 12(l):88-96; 1978.

 Karickhoff,  S.W.;  Brown,  D.S.;  Scott, T.K.  Sorption  of hydrophobia
 pollutants on  natural  sediments.  Water Res.  13:241-248;  1979.

 Kirk-Othmer    Encyclopedia  of Chemical Technology.  3rd ed . , New York,
 NY:   Interscience  Publishers; 1976.

Lillian  D.;  Smith, H.B.; Appleby, A.; Lobban, L.  ; Arntz,  R. ; Gumpert, R.-
Hague, J.; Toomey, J.; Kazazis,  J.; Antel, M. ; Hansen, D.; Scott  B
                  °f halogenated compounds.  Environ.  Sci. Technol. 9:1042-
Lyman, W.J.^Reehl, W.F.;  Rosenblatt,  D.H.  (eds.).   Handbook of  chemical
                                            ^havior of  organic  compounds.
                                   10-7

-------
 Mabey,  W. ;  Mill,  T.   Critical review of hydrolysis of organic compounds
 in water under environmental conditions.   J.  Phys. Chem.  Ref  Data
 7:383-415;  1978.

 Mackay, D.   Finding  fugacity possible.   Environ.  Sci.  Technol.  13:1218-
 x^»— j j  j» 7 / 7 •
 Mackay,  D.;  Yuen,  T.K.   Volatilization of  organic  contaminants  from
 rivers.   Proc.  14th Canadian Symp.,  1979.  Water Pollut.  Res. Can.;  no
 date.

 Mackay,  D.;  Leinonen, P.J.   Rate  of  evaporation of low  solubility  contaminants
 from water bodies  to atmosphere.  Env.  Sci. Technol.  9:: 1128-1180;  1975.

 McConnell, G.;  Ferguson, D.M. ; Pearson, L.R.  Chlorinated hydrocarbons
 and  the  environment.  Endeavor 34(12) : 13-18; 1975.

 Miller,  C.   Exposure assessment modelling,  A.  state of  the art review
 Contract EPA PB 600/3-78-065.  Athens,  GA:  Athens Research Laboratory,'
 U.S. Environmental  Protection Agency;  1978.

 Morrison, R.J.; Boyd, R.N.  Organic  chemistry.  Boston, MA:  Allan and
 Bacon; 1973.

 Neeley,  W.B.  A preliminary assessment  of  the environmental exposure to
 be expected  from the addition of a chemical to a simulated aquatic eco-
 system.   Intern. J.  Environ. Studies 13:101-108; 1979.

 Pellizzari,  E.D.; Erickson, M.C.; Aweidinger,  R.A.   Formulation of a
 preliminary  assessment of halogenated organic compounds in man and environ-
 mental media.   Washington, DC:  U.S. Environmental  Protection Agency: 1979.

 Smith, J.H.; Bomberger,  D.C.  Prediction of volatilization rates of high
 volatility chemicals from natural water bodies.   Env.  Sci. Technol
 14(11) .-1332-1337; 1980.

 Southworth, G.R.  The role of volatilization in  removing polycyclic aromatic
 hydrocarbons from aquatic environments.  Bull. Environ.  Contain'.  Toxic ol
 21:507-514; 1979.

 Stanford Research Institute (SRI) .  Estimates  of physical-chemical
properties of organic priority pollutants.   Preliminary  draft.   Washington.
DC:  Monitoring and Data Support  Division,  U.S.  Environmental  Protection
Agency;  1980.

Tabak,  H.H.;  Quaves , A.; Mashni,  C.I.;  Barth,  E.F.   Biodegradability
studies  with priority pollutant organic compounds.   Cincinnati,  OH:'
Environmental Research Laboratory, U.S. Environmental  Protection Agency;
1980 .
                                   10-8

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U.S. Environmental Protection Agency (U.S.  EPA).   Environmental
modeling catalogue.  Contract EPA 68-01-4723.   Washington,  DC:
Management Information and Data Systems Division, U.S.  Environmental
Protection Agency; 1979.

U.S. Environmental Protection Agency (U.S.  EPA).   Exposure  analysis
modeling system AETOX 1.  Athens, GA:  Environmental Systems Branch,
Environmental Research Laboratory, Office of Research and Development,
U.S. Environmental Protection Agency; 1980.

Weast, R. ed.  Handbook of chemistry and physics.  55th ed.   Cleveland,
OH:  Chemical Rubber Company; 1974.

Wilson, J.T.; Enfield,  C.G.;Dunlap, W.J.; Cosby,  R.L.;  Foster,  D.K.;
Baskin, L.B.  Transport and fate of selected organic pollutants in a
sandy soil.  Ada, OK:  Robert S. Kerr,  U.S. Environmental Protection
Agency; 1980.
                                 10-9

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10.4  MONITORING DATA AND ENVIRONMENTAL DISTRIBUTION

      Data Bases

           Environmental Contaminant Monitoring Program - U.S.D.I.

           Pesticide Soils Monitoring Program - U.S.  EPA

           NASQAN - National Stream Quality Accounting Network,  USGS

           SAROAD - Storage and Retrieval  of Aerometric Data,  U.S.  EPA
                    Research Triangle Park

           STORET - Storage and Retrieval  of Waste  Quality File,  Water
                    Quality, File,  U.S.  EPA

      Literature

           Bellar,  T.A.;  Lichtenberg,  J.J.;  Kroner, R.C.   The  occurrence
           of organohalides in  chlorinated drinking waters.  Report No.
           670/4-74-008,  U.S. Environmental  Protection Agency;
           November 1979.

           Bozzelli,  J.W.;  Kebblekus,  B.B.   Analysis  of selected  volatile
           organic  substances in ambient air.   Trenton,  NJ.  New  Jersey
           Department of  Environmental Protection;  1979.  Available from:
           NTIS,  Springfield, VA; PB 80  14469  4.

           Coniglio,  W.A. ;  Miller,  K. ; MacKeever, D,,   The occurrence of
           volatile organics in drinking water.  Washington, DC:
           Criteria and  Standards Division,  U.S. Environmental Protection
           Agency;  1980.

           Ewing, B.B.; Chian,  E.K.  Monitoring  to detect previously
           unrecognized pollutants  in  surface  waters.   Report No. EPA
           560/6-77-015a.   Washington, DC:   Office of  Toxic Substances,
           U.S.  Environmental Protection Agency; 1979.

           McConnell,  G.; Ferguson,  D.M.;  Pearson, C.R.  Chlorinated
           Hydrocarbons and  the  Environment.   Endeavor  34(121):13-18;  1975,

           National Academy  of  Science (NAS).  Drinking water and health.
           Washington, DC:   U.S. Environmental Protection Agency; 1977.
           Available  from NTIS,  Springfield, VA; PB 269519

           Pearson, C.R.; McConnell, G.  Chlorinated. C and C? hydrocarbons
           in the marine environment.  Proc. R.  Soc. London B 189:305-
           322;  1975.
                                 10-10

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Pellizzari, E.D.; Erickson, M.C.; Zweidinger, R.A.   Formula-
tion of a preliminary assessment of halogenated organic com-
pounds in man and environmental media.   Washington,  DC:  U.S.
Environmental Protection Agency; 1979.   Available from NTIS,
Springfield, VA; PB 80 112170.

Symons, J.M.; Bellar, T.A.; Carswell, J.K.; DeMarco, J.;
Kropp, K.L.; Robeck, G.G.; Seeger, D.R.; Slocum, C.J.;
Smith, B.L.; Stevens, A.A.  National organics reconnaissance
survey for halogenated organics.  J. Am. Water Works Assn.
67:634-646; 1975.

U.S. Dept. of Health, Education and Welfare (HEW),  1970.
Community Water Supply Study,  Public Health Service, Environ-
mental Health Service, Bureau  of Water  Hygiene.

U.S. Environmental Protection  Agency (U.S.  EPA) National
Organizations Monitoring Survey.  Unpubl. Washington,  DC:
Technical Support Division, Office of Water Supply,  U.S.
EPA; 1978.

U.S. Food and Drug Administration.  1974.  Total Diet  Studies.
Compliance Program Evaluation.
                       10-11

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 10.5   HUMAN EXPOSURE AND EFFECTS

       Computer-Based lexicological  Information Services
 Database

 CANCERLIT

 CANCER  PROJ



 EMIC

 ETIC

 EXCERPTA MEDICA


 MEDLINE


 NTIS
RTECS
TDB
TOXLINE/TOX3ACK
      Literature
 Accessible Through           Database Content

 National Library of  Medicine  All  asoects  of cancer

 National Library of  Medicine  Ongoing  cancer research
                              projects for most  recent
                              3 years
 Department  of  Energy

 Department  of  Energy

 Lockeed's DIALOG Service
Chemical mutagenesis

Chemical teratogenesis

Human medicine and related
disciplines
National Library of Medicine International biomedical
                             literature

Lockheed's DIALOG Service    Government-sponsored re-
                             search plus analyses pre-
                             pared by federal agencies
                             or their contractors/
                             grantees

National Library of Medicine Acute toxicity, eye/skin
                             irritation, recommended
                             exposure levels

National Library of Medicine Chemical, pharmacologic,
                             and toxicological data
                             extracted from 80 standard
                             reference textbooks, mono-
                             graphs

National Library of Medicine Human and animal toxicity,
                             effects of environmental
                             chemical pollutants published
                             within or prior to  the last
                             5  vears
           Adamson, F.; Gilbert,  D.;  Pervak,  J.;  Scow,  K.;  Wallace,  D.
           Identification and evaluation of waterborne  routes  of human
           exposure through food  and  drinking water.  Dra^t Report
           Contract EPA 63-01-3857, Task 4.  Washington, DC:   Monitorin-
           and Data Support Division,  Office  of Water Regulations and
           Standards,  U.S.  Environmental Protection Agencv;  Jan.  1980.
                                   10-12

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 Casarett, L.J.  Casarett and Doull's Toxicology:   The Basic
 Science of Poisons, 2nd ed.   New York:  Macmillan Publishing
 Co., Inc.; 1980.

 Clayton, G.D.; Clayton, F.E.  Patty's Industrial  Hygiene
 and Toxicology, 3rd revised  edition.  New York:   John Wiley
 and Sons; 1981

 Gosselin, R.E.; Hodge,  H.C.; Smith,  R.P.; Gleason,  M.N.
 Clinical Toxicology of  Commercial Products,  4th ed.
 Baltimore:  The Williams & Wilkins Co.;  1976.

 International Agency for Research on Cancer  (IARC).  Monographs
 on the Evaluation of Carcinogenic Risk of Chemicals to Man
 (series).  Lyon, France.

 International Commission on  Radiological Protection (ICRP).
 Report of the Task Group on  Reference Man.   New York, NY:
 Pergamon Press; adapted October,  1974.

 National Academy of Sciences (NAS).   Drinking water and  health.
 Washington,  DC:  NAS; 1977.

 National Cancer Institute (NCI).   Bioassays  of compounds for
 possible carcinogenicity (series).   Washington, DC:   NCI

 National Institute for  Occupational  Safety and Health (NIOSH).
 The registry of toxic effects  of  chemical substances.  HEW
 Public.  No.  (NIOSH)  76-191.  Washington,  DC:  U.S.DHEW;  1976.
 Sax, N.I.  Dangerous properties of industrial materials,
 New York:  Reinhold; 1979.

 Shepard, T.H., ed.  Catalog of teratogenic agents, 3rd edition,
 Baltimore:  John Hopkins University Press; 1980.

 Survey of Compounds Which Have Been Tested for Carcinogenic
 Activity (series).  Washington, DC: HEW GPO

 U.S. Department of Agriculture (U.S.DA).  Food consumption
 of households in the United States, spring 1965.  Report No.
 11, Food and Nutrient Intake of Individuals in the United
 States.  Stock No. 0100-1599.  Washington, DC:  U.S.
 Government Printing Office; 1972.

U.S. Department of Agriculture (U.S.  DA).  Nationwide
Food Consumption Survey 1977-1978.  Preliminary Report No.
2.  Food and nutrient intakes of individuals in 1 day in
the United States.  Spring 1977.   Washington,  DC:  Science
and Education Administration, U.S. DA; 1980.
                     1O TO
                     J-vJ— IJ

-------
U.S. Food and Drug Administration (U.S. FDA).  Compliance
program evaluation FY 1974.  Total diet studies.  Washington
DC:  Bureau of Foods, U.S. FDA; 1977.

U.S. Environmental Protection Agency (U.S. EPA).  Guidelines
and methodology used in the preparation of health effect
assessment chapter of the consent decree water criteria
documents.  Federal Register 44(52): 15641; 1979.

U.S. Environmental Protection Agency (U.S. EPA).  Water
quality criteria documents availability.  Federal Register
45(231):79318-79384;  November 28,  1980.
                    10-14

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10.6  EFFECTS AND EXPOSURE— NON-HUMAN BIOTA

      Periodicals

           Archives of Environmental Contamination and Toxicology
           Biological Bulletin
           Bulletin of Environmental Contamination and Toxicology
           Bulletin of the Japanese Society of Scientific Fisheries
           Comparative Biochemistry and Physiology
           Ecology
           Environmental  Pollution
           Fishery Bulletin
           Hydrobiologia
           Journal of Experimental  Marine Biology  and  Ecology
           Journal of Fish Biology
           Journal of Fisheries Research Board  of  Canada
           Journal of Great Lakes Research
           Journal of Invertebrate  Pathology
           Journal of Marine Biological Association
           Journal of Zoology
           Marine  Biology
           Marine  Fisheries Review
           Pesticides Monitoring Journal
           Proceeding  of the National Academy of Sciences
           Progressive Fish Culturist
          Transactions of the American Fisheries Society
          Water Pollution Control Federation
          Water Research
          Water Resources Bulletin

     Other Sources

          National Academy of  Sciences, Washington,  DC:  studies of
          pollutants .

          U.S.  Atomic Energy Commission (U.S.  AEC) .  Toxicity  of power
                                            WASH~1249'  VC-11''   Washington,
         U.S.  Environmental Protection Agency  (U.S. EPA).  Water qualit"
         criteria documents availability.  Federal Register 45P31) •   '
         /9318-79384; Nov. 28, 1980.                                '

         U.S.  Environmental Protection Agency  (U.S. EPA).  Reported fish
         kills.  Washington, DC:  Monitoring and Data Support Division "
         Office of Water Regulations and Standards, U.S. EPA, constant!-/
         updated tile.
                                 10-ij

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10.7  RISK ESTIMATION

      Albert,  R.E.;  Train,  R.E.,;  Anderson,  E.   Rationale developed by the
      Environmental  Protection Agency for  the  assessment of carcinogenic
      risk.   J.  Nat.  Cancer Inst.  58:1537-1544;  1977.

      Armitage,  P.;  Doll, R.   Stochastic models  for  carcinogenesis.
      In Lecam and Neyman  (eds.)  Proceedings of  the  Fourth  Berkeley
      Symposium on Mathematical Statistics  and Probability,  No.  4.'

      Bliss, C.I.  The  method  of  probits.   Science 79:38; 1934.

      Brewen,  J.G.   Human genetic  risk assessment for chemical substances.
      Regulatory Toxicology and Pharmacology,  1:78-83; 1981.

      Brown, C.C.  The  statistical analysis of dose-effect  relationships.
      In Butter, G.C.  (eds.) Principles of Co-Toxicology.  New York   N Y •
      Wiley &  Sons;  1978.                                           '     "

      Brown, S.M.  The  use  of  epidemiologic data in  the assessment of
      cancer risk.  J.  Environ. Path.  Toxicol. 4:573-580; 1980.

      Carlborg,  F.W.  Dose-response functions  in carcinogenesis and the
      Weilbull Model.   Fd.  Cosmet Toxicol. 19:255-263; 1981.

      Carter, L.J.  Dispute over cancer risk quantification.  Science
      203:1324-1325; 1979.

      Chand, N.; Hoel, D.G.   A comparison of models for determining safe
      levels of  environmental agents.  In Proschan,  F.; Serfling, R.J.
      (eds.) Reliability and biometry statistical analysis of life-
      length.  Philadelphia, PA:   SIAM; 1974.

      Cornfield, J.   Carcinogenic risk assessment.   Science 198:693-699;


      Cramer, G.M. ;  Ford, R.A.  ; Hall, R.L.   Estimation of toxic hazard—
      a decision tree approach.  Cosmet.  Toxicol. 16:255-276; 1978.

      Crump, K.S.;  Hoel, D.G.;  Langley, C.H.;  Petro,  R.   Fundamental
      carcinogenic  processes and  their implications  for low-dose  risk
      assessment.  Cancer Res.  36:2973; 1976.

      Eschenroeder,  A.   A summary  of  quantitative risk assessment
      approaches for  chemicals  :Ln  the environment.  Washington, DC:
     Edison Electric Institute:;  1980.

     Gehring,  P.J.;  Watanabe,  P.G.;  Park,  C.N.  Resolution  of  dose-
     response toxicity data for chemicals  requiring  metabolic  activation:
     example - vinyl chloride. Toxicol. Appl. Pharnacol. 44-581-=:91-
     1978.
                                 10-16

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  Gillette,  J.R.   Application of pharmacokinetic principles in the
  extrapolation of animal data to humans.   Clinical Toxicology
          • j  •!. .7 / O •
            ooA    reSulation of carcinogenic  hazards.   Science  208:
         ;  1980.


  Guess,  H.;  Crump,  K. ;  Peto,  R.   Uncertainty estimates for low-dose

  37:3475-3^3  1977S  °f animal CarcinoSenicit^ d*ta.  Cancer Res.


  Hartley,  H.O.; Sielken, R.L. ,  Jr.  Estimation of "safe doses" and
  carcinogenic experiments.  Biometrics 33:1;  1977.

  Higginson, J.; Muir, C.S.  Environmental carcinogenesis:  miscon-
 Hoel, D.G.; Gaylor, D.W.; Kirschstein, R.L. Saffiotti  U •
 Schneiderman, M.A.  Estimation of risks of irreversible, delaved
 toxicity.  J. Toxicol. Environ. Hlth. 1:133-151; 1975.
 Kensler,  C.J.   Experimental procedures  in the evaluation of  chemical
                                            aspects  of
 Leape   J.P    Quantitative  risk assessments  in regulation of environ
 mental  carcinogens.  Harvard Environ. Law Rev. 4:86; 1980.

 Mantel, N.; Bohidar, N.R,; Brown, D.C.; Ciminera, J.L.; Tukev  J W
 An  improved "Mantel-Bryan" procedure for "safety  testin,"  of
 carcinogens.  Cancer Res. 35:759; 1971.
                                          of
 nlr' HHC'  RelationshlPs of bioaasay data on chemicals to their
                            for
Raabe, O.G.; Book, S.A.; Parks,  SI.   Bone cancer from radium:
                     explains data  £or mi
                            10-17

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Truhaut, R.  An overview of the problem of thresholds for chemical
carcinogens.  In Davis,  W.; Rosenfeld,  C.  (eds.)  Carcinogenic risks/
strategies for intervention.  Lyon,  Fr.:IARC Scientific Publica-
tions No. 25; 1979: 191-202.

Whittemore, A.S.  Mathematical models of cancer and their use in
risk assessment.  J. Environ.  Pathol. Toxicol.  3:353-362; 1980.
                          10-13

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        APPENDIX A.  MATHEMATICAL DETAILS OF RISK  CALCULATIONS
A.I   INTRODUCTION

      In rare  instances, epidemiological studies provide direct  informa-
tion  about  the adverse effects of a substance to humans.  However, even
in these  instances, the actual exposure intensity and duration  that was
responsible for these effects may be difficult to quantify.  Consequently,
most  risk estimates for humans are based upon laboratory studies with ex-
perimental  animals.  It is preferable to base an estimate upon  several
studies with  different species, in which case a range of potency may be
established for the pollutant in question.  Wherever possible,  confidence
limits and measures of statistical significance should be introduced to
qualify these results.  Even in a single experiment, different  interpre-
tations of  the data may lead to uncertainty about the response.  Further,
the extrapolation from responses in laboratory animals administered high
doses to  the  low doses characteristics of most human exposure to environ-
ment  pollutants is necessarily an uncertain process.  Hence several
different methods should be used to establish the range of potential risk.

     A dose-response curve can be defined as a relationship between the
amount or rate of the chemical administered and the probability of the
subject experiencing an adverse effect at that dose.  Hence, the curve is
a cumulative probability distribution function and should increase from
zero  to one, assuming that higher doses are increasingly more toxic.

     The estimation of risk on the basis of experimental data involves
the selection of a hypothetical dose-response curve, and the fitting of
the parameters of this curve to the data.   Although ideally algorithms
would exist for calculations of risk due to all types of health hazards,
at the present time the only effect for which a substantial body of theory
exists is carcinogenesis.   Three different types  of dose-response models
for assessing cancer risk are described in the following sections.
            linear non-threshold model (Chand and Hoel 1974,  Cornfield
        1977, NAS 1977) is based upon the "one-hit" principle,  which
        asserts that each molecule of the substance has an equal probabilitv
        of producing a specific effect.   The resulting dose-response curve
        is exponential, and is approximated by a linear curve in the low-
        dose regions.   This method tends  to produce "upper bound" risk
        estimates, which probably exceed  the actual risk to humans.

        Tne Mantel-Bryan (log-probit) model (Bliss 1934,  Mantel et_ al.
        1971, Mantel and Bryan 1961)  assumes that the susceptibiTity"of
        receptor organisms is normally distributed with respect to the
        log of the dose.  Hence the cumulative distribution of  response
        is the integral of a log-normal density function.   The  resulting
        dose-response  curve has an S-shape,  and usually yields  lower
        estimates of risk because of  the  implied threshold effect.
                                   A-l

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     •  The multi-stage model has been independently developed  by  several
        investigators  (Armitage and Doll 1961, Crump e_t al.  1976,  Crump
        et. al. 1977, Hartley ar.d Sielken 1977) and generalizes  the linear
        one-hit model  to allow polynomial functions of dose  and time.  It
        often reduces  to a linear model in the low-dose region,  but pro-
        vides a better fit when, the data indicate that there is a  threshold
        effect.

These three methods and their application are discussed in greater detail
below.
A.2  HUMAN EQUIVALENT DOSES

     The calculation of the equivalent human dose for extrapolation of
animal data can usually be accomplished by simply multiplying the human
weight (70 kg) by the animal dose expressed in mg/kg  per day.  To cover
situations in which doses are expressed in different units, a procedure
was developed to compute  equivalent human doses for any experimental
situation.  The following formulae require knowledge of the weights,
dietary intakes, and respiration rates of the experimental animals.

Let D , D   denote human and animal doses respectively,

    W , W   denote human and animal weights (kg),

    I ,1.    denote dietary intakes (kg/day),  and
     n,  A.
                                       •^
    R ,R    denote respiration rates (m /day)
     n  A


Four cases are addressed corresponding to four different units of measure
for the animal dose D^.   In each case, the equivalent human dose is com-
puted by normalizing the intake relative to body  weight.  For skin absorp-
tion, however, DA refers not to an estimated intake, but simply to a
concentration in water.

          (i)   D  expressed in ug/day:
                                    W
               DH (ug/day)   =  DA •  Ji-


         (ii)   D  expressed as ppb in diet:


               DH (ppb)   =  D  •  -£ •  -A
                H            A   WA   IR


                                       W
               D  (Ug/day)   =  D   I   • -£
                n              A  A   W,
                                       A
                                  A-2

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          (i;Li)  D  expressed as yg/1  for skin contact:
                DH (ug/day)  =  0.002 DA

                    (this assumes human absorption of 2 ml/day of
                    water containing a pollutant)
          (iv)  DA expressed as ng/m3 for inhalation

                        3             W    R
                DR (ng/m )     .  DA . Ji ,
                                       A
                                        w
                   (yg/day)   =  D,  R  •  — •  10
                                 A   A   W,
                                         A
 In order to facilitate the application of  these formulae,  the  conversion
 cnart in Table A-l shows  numerical  conversion  factors  for  experiments
 with mice and rats.   The  approach for converting acute doses is  entirely
 analogous,  except  that the units of intake are ug rather than  ug/day.   '

      In  the case of  carcinogenic effects,  it is sometimes  assumed  that
 equivalent  doses are proportional to  body  area.   The U.S.  EPA  recommends
 me  m^0?n™f desi^ating equivalent  doses of carcinogenic substances
 (U.S.  SPA 1979).   Presumably this method reflects  a view that  carcinogenesis
 is  related  to  the  area of  some physiological membrane.  It  is  also the
 logical  choice  when  the route of exposure  is skin  absorption.  Thus:


          Weight of  substance to which human is exposed
          Body  surface area  of human

          is equivalent to

          Weight of substance to which animal is exposed
          Body surface area of animal


Because the surface areas  of similar solids are proportional to the squares
of corresponding linear dimensions  and volumes  or weights are proportional
to the cubes of corresponding linear dimensions, one can approximate  sur-
face area by weight raised to the two-thirds power.  Thus


          (Body surface area) is  proportional to (Body  Weight) 2/3
                                  A-3

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                        TABLE A-l.  FACTORS FOR CONVERTING DOSES FROM LABORATORY
                                    ANIMAL STUDIES TO HUMAN EQUIVALENT DOSES
                       ASSUMPTIONS
                                  a


Weight
Species (kg)
Human 70


Mouse 0.025

P-
4>

Uat 0.3


Rate of
Ingeation
(kg/day)
4


0.003




0.015

Rate of
Respira-
tion
(mVday)
]0.7


0.033




0.14



Dose

1 ug/day
1 ppb
1 ue/1
1 ng/m3

1 ug/day
1 ppb
1 Ug/l3
1 ng/m



HUMAN EQUIVALENT DOSE

IJg/day
Total Food

2800
8.4 4.2
0 . 00?
0.09

233
3.5 1.75
0.002
0.03

ug/1
Contact



1




1


ng/m
Breathing




8.6




3
 Equivalent human doses are assumed proportional  to weight and  rate of  intake.   Rates  of respiration
 are based on minute volume while resting (Spector 1956).
Note:    Adult mice and rats are usually  heavier  than 25  and  300  g.   Thus  the  numbers  above must  be
         used with caution.   If surface area  is used  as a normalizing factor  rather  than body  weight,
         then human equivalent doses  should be reduced by a  factor of 14  for mice  and  a  factor of
         6 for rats.

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  This has  the  effect  of  reducing  equivalent  human  doses  by  about  14  in
  the case  of mice, and by  about 6  in  the case  of rats  (Table A-l).

      In many  experiments  no  explicit  account  is taken of time.   However
  time is an explicit  variable in  the multi-stage extrapolation described'
  below, and it is an  implicit variable in all  other extrapolations.  Cancer
  occurrence increases with age in  both humans  and  experimental animals
  and is a  multi-step, time-dependent process.  For mice  and rats  the inter-
  val of the usual life span of 2-3 years is  the normal exposure interval
  for a valid carcinogenicity study.  The most plausible assumption is that
  the normal lifetime of  an experimental animal is  equivalent to the normal
  lifetime  of a human.

      Procedures for estimating human equivalent doses often account for
  time factors in several ways:

      •  If the substance was administered to experimental animals on an
         intermittent basis,  e.g., 5 days per week, then the assumed dose
         is reduced by a corresponding factor,  e.g.,  5/7.

      •   If the duration of exposure was  shorter than the experimental
         animal lifetime, then the assumed  dose is  reduced by the  ratio
         of those times,  i.e., duration/lifespan.

 It should  be noted  that  such procedures  do  not take  into account  the
 relevant phannacokinetics, and are merely  a device for reducing the  dose
 and hence  obtaining  a more conservative  risk estimate.   They  generally
 do not  affect  the results  by more than a factor of 50%,  which  is  small
 compared with  the total  range of  uncertainty.  Uncertainties due  to  dose
 estimation and techniques  of  extrapolation  can often span several orders
 of magnitude.
A. 3  ONE-HIT MODELS

     The "one-hit" models describe a mechanism of carcinogenesis in which
a single event triggers the cancer.  The event may be a molecule of the
carcinogenic substance reaching a suitable receptor site or it may be
some more complex but undescribed happening.  The basic supposition is
that the probability of this event in a short time interval dt (short
compared witn the time of observation, which is usually the major part
of a lifetime) is proportional to the duration of the time interval   The
factor of proportionality, called the "hazard function," may be a function
of time and or the dose level.  Thus the hazard function is written
h(x,t)  where x is the dose level and t is time,  measured in lifetimes.
to dost:^ Unear extrapolation- this function is taken to be proportiona


                          h(x,t)   =  bx                                _
                                   A-5

-------
where b  is  a  factor of proportionality and x is the dose level.  The
probability of a  "hit," that is, initiation of cancer, is proportional
to  the duration of a time interval:


          P (initiation of cancer in the interval  (t,t = dt)}

          =  bx dt


In  this  form  one can see the reason for calling the extrapolation linear—
doubling the  dose, for example, doubles the probability of initiating
cancer.

     The multi-stage model generalizes this approach, replacing the
product bx  by the product of two polynomials, one a polynomial in t, the
other a polynomial in x.
          h(x,t)  = IV t1  £b.x:i                                 (A-2)
This approach allows a great deal of flexibility, though as a practical
matter the polynomials cannot be too large or one loses track of their
significance.

     Let Q(x,t) be the probability that no cancer has been initiated in
the interval (0,t) when the animal has been subjected continually since
time 0 to a dose level of x.  The second underlying assumption is that
the probability of initiating cancer at any particular time is independent
of whether or not cancer has previously been initiated; this assumption
allows us to multiply probabilities and


          Q(x,t + dt)  =  Q (x,t)  (1 - h(x,t)dt).                    (A-3)


Rearranging terms


          |£+h(x,t)Q  =  0
          ot

             Q(x,t)   =  exp [- /Qh(x,t)dt]                           (A-4)
                                 A-6

-------
 Let P(x,t)  be the probability that cancer is  initiated in the interval
 (0,t)
           P(x,t)   -  1 - Q(x,t)

                   =  1 - exp  [-/Ti(x,t)dt]                           (A-5)


 P(x,t)  can also be identified as  the  cumulative  distribution  function
 for  the random variable "time until cancer  is  initiated" — that  is,  the
 probability that  the  time until cancer  is initiated  is  less than  t  is
 P(x,t).   The derivative dP/dt is  the  probability density  function f(x,t)
 for  these intervals



           «"'>   '  I

                   =  h(x,t) exp [-/Ch(x,t)dt]
                                   o
                   =  h(x,t) Q(x,t)                                   (A-6)


 The  function f(x,t)dt  has the  interpretation of  the probability that
 cancer  is  initiated in the interval (t,t+dt).  Finally, we note that
 h(x,t)dt   =  f (x,t)dt/Q(x,t) can be interpreted as the probability  that
 cancer  is  initiated in the interval (t,t+dt) given that it has not been
 initiated  up until  time  t.


A. 4  LINEAR  EXTRAPOLATION

     In the  linear extrapolation h(x,t)  is given by Equation (A-l) .


          Q(x,t)   =  e~bxt                                         (A_7)
          P(x,t)  =  1 - e'                                        (A_8)


If there is a "background" or "spontaneous" cancer incidence present
even when the dose rate of the toxic substance is zero,  then one can use
either of two smaller approaches.   One can assume that h(x,t)  has the
form
          h(x,t)   =  bx + c
                                                                   (A-9)

-------
in which case
          Q(x,t)  =  e~Ct e~

          P(x,t)  -  1 - e~Ct e                                    (A-ll)
At Che conclusion of the experiment one can identify the fraction of
animals in the control group which contracted cancer in spite of the fact
they were not intentionally subjected to a carcinogen as the probability
9 of "spontaneous" cancer.   Then it is easy to see from Equations
(A-10) and (A-ll) that
          Q(x,t)  =  (1 - 9)e

          P(x,t)  =  1 - (1 - 6)e~bxt                              (A-13)
and hence
          9=1- e~Ct                                            (A-14)
Having measured 9 by observing response in the control group, one could
infer the value of c, but this is usually not done.

     Alternatively, one can determine both parameters b and c by a data-
fitting procedure involving the maximum likelihood estimators.  This is
the multi-stage procedure when two non-zero parameters in the polynomials
are permitted.  It is detailed below.

     We have noted that ?(x,t) is the cumulative distribution function
for the random variable  time-to-initiation-of-cancer.  P(x,t) as a func-
tion of t has the form shown in Figure A-l.
                   y                                            t  or x

            FIGURE A-l.   CUMULATIVE DISTRIBUTION FUNCTION ?(x,t)


                                  A-8

-------
 Obviously,  from Equation (A-13),  P(x,t)  considered as a function of x
 has the same form as that when it is considered a function of t.  For
 this reason it is common to regard P(x,t)  as the cumulative distribution
 function of a random variable called susceptibility.   Thus, the fraction
 of experimental animals in whom cancer is  initiated at dose x is regarded
 as a group  of animals in whom tolerance  is less than or equal to x.  This
 logical transition from a determinate parameter of the experiment, the
 dose x, to  a random variable, tolerance,  is plausible but not necessarily
 correct.  P(x,t)  is measured by  giving a  group of animals the dose x and
 noting the  fraction in whom cancer is initiated.  It  is conceivable that
 P(x,t)  as a function of x could  increase  as the dose  increases and then
 decrease  if, for example, high doses brought into play a new mechanism,
 such as vomiting, not encountered at low doses.  It is important to recog-
 nize that consideration of  the dose-response curve as  the cumulative distri-
 bution function of a random variable, tolerance, requires the supposition
 that P(x,t)  as a function of x increases monotonically.

      The  most rigorous mathematical procedure for estimating the para-
 meters  b  and c (or b and 6)  is maximum likelihood estimation.   More
 commonly, experimenters simply plot the fractions of animals in which
 cancer  is found at the conclusion of the experiment at time T and use
 these fractions as estimates of  the parameter P(.x,t).   In the linear
 extrapolation,  it is customary to expand P(x,T)  about  zero.
          ?(x,T)  -   1 -  (1 - 0)  (1 - bxT)

                  -   9 +  bxT                                       (A-14)


and to fit a straight line to the data points P' (xi,T)  =
P(x-j_,T) - 3  =  bxj_T.  Because the expansion in Equation (A-14) is
valid only for small x, one should use data where x is as small as
possible.

     It should be noted that the crucial supposition in the linear model
is the selection of the form for h(x,t) given in Equation (A-l).  The
consequence of this selection is that the curve for P(x,t) in the
vicinity of x = 0 will have a positive slope.  Because the data are
gathered for relatively large values of x, the experiment does not test
this supposition and therefore belief in the linear model amounts to an
assumption.  It is often argued that the real situation is unlikely to
be worse than this and that therefore the linear model provides a con-
servative estimate of risk.
A.5  LOG-PROBIT EXTRAPOLATION

     Log-probit extrapolation (also called Mantel-Bryan extrapolation
after the original proponents of the method) assumes a different form
for the dose-response curve.   Specifically, it assumes that the logarithm
                                 A-9

-------
of  tolerance  is normally distributed.  There  is little  theoretical
underpinning  for  this assumption, though a number of physiological
variables  (such as heights of humans) seem to  follow this  log-normal
distribution.

     The mathematical form of the dose-response curve is
          P(x,T)
                    a + b log1Qx
                               - 1/25
                                                                   (A-15)
On log-normal graph paper this function is a straight line with a slope
of b probits (standard deviations) per decade of change in the dose x
and a y-intercept of a probits, as shown in Figure (A-2).

     The steeper (or the larger) the slope of this line the smaller the
values of P(x,t) found by extrapolations to small values of x (large
negative values of log x).  One could plot the data and fit a straight
line, either by eye or by some analytical procedure:, thus finding values
for the parameters a and b.   However, the more common procedure is to
set b = 1 and to find the best fit to the data of a line with this slope
It is argued that b = 1 is the shallowest slope observed over a wide
variety of carcinogens already studied and that selecting a line with
unit slope is therefore conservative.
                        -a       0                       log x

             FIGURE A-2.   LOG-PROBIT  FORM  FOR DOSE-RESPONSE  CURVE
                                  A-10

-------
  The supposition that the slope b - 1 is, of course, somewhat arbitrary
  r^ J          significant than the equally arbitrary supposition that
  the dose-response curve should be described by Equation (A-15).
 in^       r       that f°r large ne§ative values of the variables of
 integration 5 the integrand in Equation (A-15) is very small.  In fact
 the function exp (-52) and all its derivatives vanish' as t-  - -»   For '
 this reason the log-profait extrapolation generally yields extremely low
 actuallvV  eXtrap°lated risks at low dose levels.  For the numbers
 on tS otherOUtnfd1ffn experjments on one h^ and in the  environment,
 ™1£ !   ?  u  ?  dlfference between extrapolated risk by the log-probit
              6 llnar raethod ca» ^e several
                                      several orders of magnitude.    he
 lo  nrnr            .                                 magntue.     e
 If         extrapolation is  therefore  regarded  as  a  probable  low  estimate
 of
          r                                                         smat
          risk  and  the two  methods  are  often taken as  a way of  bracketin*
  the true risk.   It is important  to recognize that both method, produce
  results  strongly dependent on  the  presumed  form  of the dose-response  '


       It  should also be noted that  this method can deal only with  the
  aifference between response at a dose x and  response when  x =  0  (the
  spontaneous" rate),  since log 0 -  -~.  Thus, there is  no  Possibilitv
  of  titting a line  or  a curve through the datum when x  - 0.

      Multi-Stage Extrapolation
  exv              extraP°lation ^ a one-hit model in which more
thus  nt 1?  f         ^ the f°rm °f the hazard function h(x,t).  It
addition Sf   ^ Presuppositions about the dose-response curve.  In
         '            f T & mOre rig°r°US "«hematical procedure for
 estimat     *         f                              ca  proceure fo
 estimating the value of the unknown parameters,  and it takes exnlic-'r
            the Ci— -^^tion-of-cancer whoever theL dat^are


      In order to avoid confusing generality we shall adopt a soecific

           h(x,t)  -  ax+bx+c

                                 to be £ound from
          P(x,t)  =  1 - exp [-(ax2 + bx + c)t]                   (A_17)
S'c 'Ythef^sl "^ doae-rMP°°" C— « any time.   We note that
   c ^ u tnere is a  spontaneous" incidence of cancer;  if b * 0,  the
                                  A-ll

-------
                                                              2
extrapolation to low doses is linear; by including the term ax  we allow
for the possibility that response at low doses may not be linear, in
which case we would expect to find a £ 0, b = 0.

     Most available data record only the number of animals which had
cancer at the conclusion of the experiment.  For such experiments we
have a sample of P(x,T) for various values of x.  Sometimes the number
of animals with cancer at some intermediate time is reported in which
case we have samples of P(x,T-j) for other values of T and various values
of x.  Occasionally when the cancer can be detected without killing
the animal (as in the case of skin cancers) one has the time-to-initiation-
of-cancer as well as dose for each animal.  The multi-stage method
accommodates all these possibilities and produces the values of a, b,
and c which best fit the totality of the data.

     Since none of the data available in these studies records time-to-
time initiation-of -cancer for each animal, we shall not carry the terms
necessary to accommodate these data in the mathematical development
which follows.  The likelihood function L is the product of terms of
the form P(x,t) given by Equation (A-17) and its complement Q(x,t) =
1 - P(x,t).


                N         n.          N. - n
          L  = n  P(x.,t )  X Q(x.,t ) 1    ±                      (A-18)
where i is the index for the S experimental data points ,  each of which
has a value for x^ and t^ associated with it; and n^_ is the number of
positive responses, Nj_ is the total number of animals and N^ - n^ is
the number of negative responses
          log L  =2  n. P(x.,t.) + (N.  - n.) Q(x.,t.)             (A-19)
                       111      ii     -LI
The standard procedure is to differentiate Equation (A-19) with respect
to the unknown parameters and. to set the derivatives equal to zero in
order to find the maximum of log L.   However, it is more convenient
simply to seek the maximum of log L  by a hill-climbing method.  One
selects initial values of a, b, and  c, and then evaluates log L with
small changes, first of a, then of b, then of c, then of a again, etc.,
continuing this procedure until log  L begins to decrease.  In this way
one can find the values of a., b, and c that maximize log L or L.  These
are the maximum likelihood estimators.

     If it should turn out that a =  0, then the result obtained is
equivalent to the linear extrapolation found earlier.   In the former
case, however, we imposed the form from the beginning;  here we have
allowed the data to produce the form.  Note, too,  that this method
                                 A-12

-------
automatically introduces variations in the duration of an experiment
and that it automatically weights data where many animals are involved
more heavily than data where only a few are involved.  For these reasons
the multi-stage method seems superior to either the linear extrapolation'
or the log-probit extrapolation.
                              A-13

-------
                               REFERENCES
Armitage, P.; Doll, R.  Stochastic models for carcinogenesis.  In
Lecam and Neyman  (eds),  Proceedings of the Fourth Berkeley  Symposium
on Mathematical Statistics and Probability, No. 4.

Chand, N.; Hoel, D.G.  A comparison of models for determining safe levels
of environmental agents.  In Proschan, F. ; Serfling, R.J. (eds),
Reliability and Biometry Statistical Analysis of Lifelength. Philadelphia,
PA: SIAM; 1974.

Cornfield, J.  Carcinogenic risk assessment.  Science 198:693-699; 1977.

Crump, K.S.; Hoel, D.G.; Langley, C.H.; Peto, R.  Fundamental carcinogenic
processes andtheir implications for low-dose risk assessment.  Cancer
Res. 36:2973; 1976.

Crump, K.S.; Guess, H.A.; Dial, K.L.  Confidence intervals and tests of
hypotheses concerning dose response relations inferred from animal
carcinogenicity data.  Biometrics 33:437; 1977.

Hartley, H.O.; Sielken, R.L., Jr.  Estimation of "safe doses" and
carcinogenic experiments.  Biometrics 33:1;  1977.

Mantel, N. Bohidar, N.R. ; Brown, D.C.;  Ciminera, J.L,,; Tukey, J.W.  An
improved "Mantel-Bryan" procedure for "safety testing" of carcinogens.
Cancer Res. 35:759; 1971.

Mantel, N.; Bryan, W.R.  "Safety" and testing of carcinogenic agents.
J. Nat. Cancer Inst.  27:455;  1961.

National Academy of Sciences  (NAS).   Drinking water and health.
Washington, DC:  NAS; 1977.

Spector, W.S. (ed.)  Handbook cf biological  data.   Philadelphia.  PA:
WB Saunders Co.; 1956.

U.S. Environmental Protection Agency (U.S.  EPA).  Water quality  criteria.
Federal Register 44:1526-1594;  1979*.
                                  A-14

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