I
EPA-560/1-75-003
             PAPERS OF A SEMINAR
                        ON
           EARLY  WARNING  SYSTEMS
            FOR TOXIC  SUBSTANCES
   i
CONFERENCE REPORT
OFFICE OF TOXIC SUBSTANCES
ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
JULY 1975

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EPA-560/1-75-003
                         PAPERS OF A SEMINAR


                                 ON


             EARLY WARNING SYSTEMS FOR TOXIC SUBSTANCES
                           Cosponsored by
                   Environmental Protection Agency
         National Institute of Environmental Health Sciences
                     National Science Foundation
                           Project Officer

                           Benigna Carroll
                 Contract #68-01-2108  Id Systems 73
                            Prepared for

                     Office of Toxic Substances
                   Environmental Protection Agency
                       Washington, B.C.   20460

                            July,  1975

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Views expressed in these papers are
those of the authors and do not
necessarily reflect the positions of
those sponsoring organizations.

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                          TABLE OF  CONTENTS


                                                                Page

Introductory Remarks, Frank A.  Butrico,
   Pan American Health Organization ...  ...........     1

Early-Warning System for Toxic  Substances:
   Human Health Effects, Anthony V. Collucci
   and Paul E. Brubaker ....................     5

Landscape Geochemistry and Environmental
   Problems, John A. C. Fortescue ...............     13

Legislation and Laws Concerning Early Warning Systems
   for Toxic Substances, Michael B.  Brownlee  .........     35

An Incident of Industrially Related Toxic Peripheral
   Neuropathy, Bobby F. Craft .................     45
Establishing Environmental Priorities for Synthetic
   Organic Chemicals:  Focusing on the Next PCB's
   Philip H. Howard ......................     51

A Laboratory Model Ecosystem as an Element in
   Early-Warning Systems for Toxic Substances,
   Robert L. Metcalf  .....................     66

Methods for Detection of Teratogenic Agents,
   T. H. Shepard, Allan Fantel, and Ted Regimbal  .......     81

The World Health Organization's Environmental
   Health Criteria and Air Monitoring Programs,
   F. Gordon Hueter, S. David Shearer, and
   Gerald G. Akland   .....................     82

A Cost-Risk-Benefit Analysis of Toxic Substances,
   Dennis P. Tihansky   ....................     83

The Problems With Early-Warning Systems for
   Toxic Materials, W. Fulkerson   ...............   118

1974 - A Year of Transition
   Glenn E. Schweitzer  ....................   119

Review of Health/Environmental Systems WitJi
   Potential Early Warning Applications,
   Theodore James Thomas and James E. Flinn  ..........   128

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                      TABLE OF CONTENTS
                            (Continued)

                                                             Pace
A Research Program to Acquire and Analyze
   Information on Chemicals That Impact on
   Man and His Environment, Arthur A. McGee
   and Kirtland E. McCaleb	151

National Cancer Institute Program of Cancer
   Surveillance, Epidemiology and End Results
   Reporting (SEER Program), James L. Murray
   and Sidney J. Cutler	154

Environmental Impact of Chemicals,  Robert J. Moolenaar .      167

Environmental Stressor Matrix System for Early Warning,
   David Li. Morrison	175

Public Interest Methods for Assessing Chemical
   Hazards, Albert J. Fritsch	196

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                              FOREWORD
      These proceedings present the results  of a 3-day seminar held at
Battelle's Seattle Research Center early in 1974.  The purpose of the
seminar was to examine some of the tools  that currently exist which may
be applicable to the early identification, assessment and prioritization'of
chemical substances that impact adversely on man or his environment. The
need for early warning tools is clearly evident when one considers (1) the
large number of chemicals to which people are exposed in their daily lives
and (2) the well-public! zed incidences involving such chemical substances
as mercury, thalidomide,  polychlorinated biphenyls,  and, most recently,
vinyl chlorides.   In principle, there are two  or three points  in the lifespan
of a chemical where early identification of potential hazards can be attempted.
For new substances this would be at a reasonably early point in the laboratory
pilot scale-commercialization sequence.   For substances already commer-
cialized and in use,  identification before the level of usage increases sig-
nificantly or the substance is incorporated into a new product line or use
category is desirable.  In each case, one is  faced with the problem of
identifying candidate substances and deciding which among them present the
more significant hazard so that the allocation of limited resources for their
study and control can be made.

      Many institutions  face a similar problem of early identification of
problem substances, although usually the domain of concern is a relatively
narrow one. For example, NIOSH focuses on the work place, NCI on
carcinogens, etc.

      Participants in this seminar were invited from a cross  section of
organizations concerned with early warning  systems.  Thus, representation
was a mixture of U. S.  government agencies,  industry, research institutes,
universities, Canadian  government agencies, and a public-interest group.
Names  of the participants  are appended to the proceedings.

      Not all the  speakers provided written papers.  Where possible,  ab-
stracts of missing papers  are included. The papers submitted are arranged
in the order of their delivery at the seminar.  A detailed seminar program
is also  appended.

      While no solutions to the problem of identification before-the-fact of
toxic substances  was arrived at,  or even expected, a number of issues
regarding the need for,  workability and practicality of, early warning were
raised.  Continued examination of the subject would be desirable.


                                           James E. Flinn*
                                           Arthur A. Levin**

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                      SEMINAR

                        ON



     EARLY WARNING SYSTEMS FOR TOXIC SUBSTANCES

                    Cosponsored by

            BATTELLE MEMORIAL INSTITUTE
         ENVIRONMENTAL PROTECTION AGENCY-
             OFFICE OF TOXIC SUBSTANCES
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
            NATIONAL SCIENCE FOUNDATION



              January 30 — February 1, 1974
        BATTELLE'S SEATTLE RESEARCH CENTER
               4000 Northeast 41st Street
               Seattle, Washington 98105

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                             PROGRAM

 Tuesday —January 29, 1974
       7:00- 9:00   Registration and Mixer at the Center
 Wednesday - January 30, 1974
       8:30- 9:00   Registration at the Center
            9:00   Welcome, T.W. Ambrose, Battelle's Seattle Research
                     Center
            9:05   Introductory Remarks, Mr. Frank Butrico, Battelle
                     Memorial Institute
            9:15   Keynote, Dr. Norton Nelson, New York University
                     Medical Center
 SESSION I         EFFECTS, LEGISLATION, AND INCIDENTS
                   Chairman Farley Fisher, Office of Toxic Substances,
                   Environmental Protection Agency
            9:45   Session Chairman's Comments
            9:50   Human Health Aspects — Anthony Colucci and Paul
                     Brubaker, NERC-Research Triangle Pa~k,
                     Environmental  Protection Agency
           10:20   Coffee Break
           10:50   Environmental Aspects  — John Fortesque, 3rock
                     University, Canada
           11:20   Legislation and Laws — Michael B. Brownlee, U.S.
                     Senate Commerce Committee Staff
           12:00   LUNCH
            1:00   An Incident of Industrially Related Toxic Peripheral
                     Neuropathy—Bobby F. Craft, National Institute
                     of Occupational Safety and Health
            1:30   An Industry's Experience — Elmer P. Wheeler, Monsanto
                     Company
            2:00   Coffee Break
            2:20   Panel Discussion on Institutional Perspectives of Early
                     Warning—Chairman Otto Bessey, National
                     Institute of Environmental Health Sciences
Thursday — January  31, 1974
SESSION II         EARLY WARNING SYSTEM ELEMENTS
                   Chairman Ronald S. Goor, National Science Foundation
            9:00  Session Chairman's Comments
            9:05  General System Requirements—Benigna S. Carroll,
                     Environmental Protection Agency
            9:35   Establishing Priorities for Synthetic Organic Chemicals-
                     Philip H. Howard, Syracuse University Research
                     Corporation

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          10:05   Proposed International Registry on Potentially Toxic
                    Chemicals—Cyrus Levinthal, Columbia University
          10:35   Coffee Break
          10:55   Model Ecosystems and Toxic Substances—Robert L.
                    Metcalf, University of Illinois
          11:25   Anticipating Hazards of Low Level Exposure to Toxic
                    Substances—Cyrus Levinthal, Columbia University
          11:55   Methods for Detection of Teratogenic Agents—Thomas
                    H. Shepard, A. Fantel, T. Regimbal, University of
                    Washington
          12:30   LUNCH
           1:30   Environmental Health Criteria and Monitoring Programs
                    of the World Health Organization—F. Gordon Hueter,
                    Environmental Protection Agency
           2:00   Should Assessment Include Cost-Benefit Tradeoffs-
                    Dennis P. Tihansky and Harold V. Kibby, Environmen-
                    tal Protection Agency
           2:30   Problems with Early Warning Systems for Toxic Materials-
                    W. Fulkerson, Oak Ridge National Laboratories
           3:00   Coffee Brealf
           3:20   Panel Discussion on Early Warning System Elements-
                    Chairman John L. Buckley, Environmental Protection
                    Agency
           5:30   SOCIAL HOUR
           6:30   BANQUET-Speaker, Glenn L. Schweitzer, Director,
                    Office of Toxic Substances, Environmental Protection
                    Agency
Friday — February 1, 1974  '
SESSION III       EARLY WARNING SYSTEMS/SUBSYSTEMS
                  Chairman James E. Flinn, Battelle's Columbus
                     Laboratories
           9:00   Session Chairman's Comments
           9:05   Review of Health/Environment Systems with Potential
                     Early Warning~Applications—Theodore J. Thomas
                     and James E. Flinn, Battelle's Columbus Laboratories
           9:35   Program to Acquire and Analyze Information on
                     Chemicals Impacting Man and Environment-
                     Arthur A. McGee and Kirtland E. McCaleb, Stanford
                     Research Institute
           10:05   NCI Program of Cancer Surveillance, Epidemiology,
                     and End Results Reporting (SEER Program)—James
                     E. Murray, National Cancer Institute, Department of
                     Health, Education, and Welfare
           10:35   Coffee Break

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10:55   Environmental Impact of Chemicals—Robert J.
          Moolenaar, Dow Chemical Company
11:25   Environmental Stressor Matrix System for Early Warning-
          David L. Morrison, Battelle's Columbus Laboratories
11:55   Public Interest Methods for Assessing Chemicals-
          Albert Fritsch, Center for Science in the Public
          Interest
12:30   LUNCH
 1:30   Panel Discussion on the Concept of Early Warning,
          Existing Systems, Research Needs, and Implementa-
          tion—Chairman David L. Morrison, Battelle's Columbus
          Laboratories
 4:00   ADJOURN

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                 EARLY WARNING SYSTEMS FQR.TOXIC SUBSTANCES

                             January 30  February  1,  1974

                           Battelle's Seattle Research Center
                                  List of Participants
Dr. Tommy W. Ambrose
Executive Director
Battelle
Seattle Research Center
4000 N.E. 41st Street
Seattle, Washington  98105

Dr. Otto A.  Bessey
•National Institute of Environmental
  Health Sciences
P. O. Box 30276
Be the s da, Maryland 20014

Dr. Stephen L. Brown
Stanford Research Institute
333 Ravenswood Avenue
Menlo Park, California 94025

Dr. Michael B. Brownlee
U. S. Senate Committee on Commerce
501 Senate Anne'x
Washington,  D. C.  20510

Dr. James E. Brydon
Environmental Protection Service
Environment Canada
Ottawa,  Ontario
Canada K1A OH3

Dr. John L.  Buckley
Office of Program Integration
Office of Research and Development
Environmental Protection Agency
Waterside Mall
401 M Street, S.W.
Washington,  D. C.  20460

Mr. Frank A.  Butrico
Battelle Memorial Institute
Washington Operations
2030 M Street, N.W.
Washington, D. C.  20036

 Mrs. Benigna Carroll
 Environmental Protection Agency
 Office of Toxic Substances
 Room 709 East
 401 M Street, S.W.
 Washington, D. C.  20460
Dr. Emil E.  Christofano
Hercules, Incorporated
910 Market Street
Wilmington, Delaware  1989C

Dr. Anthony Colucci
Pesticide k Toxic Substances
 Effects Laboratory
Environmental Protection Agency
Research Triangle Park,
North Carolina 27711

Dr. Bobby F. Craft
National Institute for  Occupational
 Safety and Health
U. S. Post Office and Court House
 Building, Room 543
Cincinnati, Ohio  45202

Mr. Gaynor W. Dawson
Battelle
Pacific Northwest Laboratories
P.  O.  Box 999
Richland, Washington 99352

Dr.  William  C. Denison
Department of Botany
Oregon State University
Corvallis,  Oregon  98331

Dr.  Robert L. Dixon
National Institute of Environmental
  Health Sciences
P.  O.  Box 12233
Research Triangle Park,
North  Carolina  27709
 Dr. Jean-Jacques Dufour
 Battelle, Geneva Research Centre
 7,  route de Drize
 1227 Carouge -Geneva
 Switzerland

 Dr. Farley Fisher
 Environmental Protection Agency
 Office of Toxic Substances
 401 M Street, S.W.
 Washington, D. C.   20460

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 Dr. James E.  Flinn
 Battelle
 Columbus Laboratories
 505 King Avenue
 Columbus, Ohio 43201

 Dr. John Fortescue
 Department of Geological Sciences
 Brock University
 St,  Catharines, Ontario
 Canada

 Dr. Virgil H.  Freed,  Director
 Environmental Health Sciences Center
 Oregon State University
 Corvallis, Oregon 97331

 Dr. Ralph I. Freudenthal
 Battelle
 Columbus Laboratories
 505 King Avenue
 Columbus, Ohio 43201

 Dr. Albert J.  Fritsch, Director
 Center for Science in  the
  Public Interest
 1779 Church Street, N.W.
 Washington, D.C. 20036

 Dr. William Fulkerson
 Oak Ridge National Laboratory
 Building 3550
 P. O. BoxX
 Oak Ridge, Tennessee 37830

 Dr. John Garner, Director
 Experimental Biology Lab
 Environmental Protection Agency
 National Environmental Research
  Center
 Research Triangle Park,
 North Carolina 27711

 Dr. David George, Director
 Center  for Human Toxicology
 University of Utah
 Salt Lake City, Utah  84112

 Dr. James H.  Gibson
 Natural  Resources Ecology Lab
 Colorado State University
 Fort Collin, Colorado 80521

 Dr.  Ronald S. Goor
 Division of Environmental Systems
 and Resources
National Science Foundation
 1800 G Street,  N.W.
Washington, D.C.  20550
Professor W. LeRoy Heinrichs
Obstetrics and Gynecology
BB 619 University Hospital RH-20
University of Washington
Seattle, Washington  98195

Dr. Philip Howard
Research Scientist
Syracuse University Research
Merrill Lane
University Heights
Syracuse, New York  13210

Dr. F. G. Hueter
National Environmental Research
  Center
Environmental Protection Agency
Research Triangle Park,
North Carolina 27711

Dr. Charles  F. Jelinek
Division of Chemical Technology
Bureau of Foods
Food and Drug Administration
Federal Building  8, Room 4013
200 C Street, S.W.
Washington,  D.C. 20204
Dr. Harold V. Kibby
Environmental Protection Agency
Office of Research and Development
Implementation Research Division
Washington, D.C. 20460

Dr. Herman Kraybill
National Cancer Institute
Room C-337
Landow Building
7910 Woodmont Avenue
Be the s da, Maryland 20014

Dr. William Lappenbusch
Environmental Protection Agency
1200-6th Avenue
Seattle, Washington  98006

Dr. Allen S. Lefohn
Environmental Protection Agency
National Ecological Research Lab
200 S.W.  35th Street
Corvallis,  Oregon 97330

Dr. Arthur A. Levin
Battelle Memorial Institute
Washington Operations
2030 M Street, N.W.
Washington, D.C. 20036

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Dr. Cyrus Levinthal
Biology Department
Columbia University
New York, New York 10027

Dr. Carson A. Lute
Battelle
Columbus Laboratories
505 King Avenue
Columbus,  Ohio 43201

Dr. Kirtland E. McCaleb
Stanford Research Institute
333 Ravens wood Avenue
Menlo Park,  California   94025

Dr. J. Roger McDonough
Director, Laboratory of
  Industrial Medicine
Tennessee Eastman Company
Kingsport, Tennessee 37662


 Dr. Arthur A.  McGee
 Stanford Research Institute
 333 Ravenswood Avenue
 Menlo Park, California  94025

 Dr. Robert Metcalf
 Department of Entomology
 University of Illinois
 583 MorriU Hall
 Urbana, Illinois

 Dr. Robert J. Moolenaar
 Environmental Affairs
 The Dow Chemical Company
 2040 Dow Center
 Midland, Michigan  48640

 Dr. David L. Morrison
 Battelle
 Columbus Laboratories
 505 King Avenue
 Columbus, Ohio  43201

 Dr. James Murray
 Biometry Branch
 Department of Health, Education,
  and Welfare
 National Cancer Institute
 Bethesda, Maryland 20014

 Dr. Norton Nelson
 New York University Medical Center
 550 First Avenue
 New York, New York 10016
Dr. Doug E. Olesen
Battelle
Pacific Northwest Laboratories
Battelle Boulevard
Richland, Washington  99352

Dr. Boris Osheroff
Special Assistant to the Assistant
 Secretary for Health
Dept. of Health, Education, and
 Welfare
HEW North, 4th and C  Streets
Washington, D.C. 20203

Dr. Jim F.  Park
Battelle
Pacific Northwest Laboratories
Battelle Boulevard
Richland, Washington  93352

Dr. Warren Piver
National Institute of Environmental
  Health Sciences
National Environmental Health
  Sciences Center
P. O. Box 12233
Research Triangle  Park,
North Carolina  27709

Lt. Col. LeRoy H.  Reuter
Chief, Sanitary Engineering
  Research
U. S. Army Medical R&D Command
Forrestal Building
Washington, D.C.  20314

Dr.  Robert A. Scala
c/o Medical Research Division
Esso Research and Engineering Co.
Linden, New Jersey   07036

Dr.  Edward A. Schuck
Monitoring Systems Analysis Staff
Monitoring Systems Research and
  Development Laboratory
National Environmental Research
  Center
P. O. Box  15027
Las Vegas, Nevada 89114

Dr. Glenn E. Schweitzer
 Environmental Protection Agency
Office of Toxic Substances
401 M Street,  S.W.
 Washington, D.C.  20460

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Dr. C.  Boyd Shaffer
American Cyanamid Company
Berdan  Avenue
Wayne,  New Jersey 07470
Dr. Thomas H. Shepard
Department of Pediatrics
Central Laboratory for Human
  Embryology RD-20
School of Medicine
University of Washington
Seattle, Washington  98195

Dr. Al J. Shuckrow
Battelle
Pacific Northwest Laboratories
Battelle Boulevard
Richland, Washington  99352

Dr. Louis G. Swaby
Equipment and Techniques Division
  (RD-688)
Research and Development
Environmental Protection Agency
Washington, D. C. 20460

Dr. Andreas Thaer
Battelle-Institut e. V.
6000 Frankfurt/Main 90
Postschliessfach  900160
Germany

Dr. Theodore J.  Thomas
Battelle
Columbus Laboratories
505 King Avenue
Columbus,  Ohio   43201
Dr. Dennis P. Tihansky
Environmental Protection Agency
1921 Jefferson Davis Hiway
CM2, Room  1006
Arlington, Virginia 20460

Dr. Peter Toft
Bureau of Health Hazards
Environmental Health Centre
Tunney's Pasture
Ottawa, Ontario
Canada K1A  OL2

Dr. Henry J. Trochimowicz
Haskell Labaratory for Toxicology
  and Industrial Medicine
E. I.  du Pont de Nemours & Co.
Newark, Delaware 19711
Dr. Ralph C. Wands, Director
Advisory Center for Toxicology
National Academy of Sciences
2101 Constitution Avenue
Washington, D. C.  20418

Dr. Elmer P. Wheeler, Director
Environmental Health Medical Dept.
Monsanto Company
800 N. Lindberg Boulevard
St. Louis, Missouri 63116

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                     INTRODUCTORY REMARKS

                         Frank A. Butrico
                 Pan American Health Organization
                        Washington,  D.  C.
      It has long been recognized that decision makers need informa-
tion to evaluate the present and potential hazards of environmental con-
taminants, and to have this information in advance of a problem be-
coming a crisis.  Also, it is becoming evident that decisions made in
reaction to a crisis are less effective.

      In these opening remarks, may I share with you some back-
ground information.

      My first exposure to the  need for early warning was back in I960
when the Environmental Sciences and Engineering Study Section at NIH
planned a conference on the physiological aspects of water quality.
The basic concept of the conference was to delineate the physiological
and toxicological factors of chemical constituents in water.  The con-
ference examined the significance of trace minerals and what were
referred to as exotic chemical substances in water supplies, and can-
cerous hazards that may be associated with  natural and artificial water
pollutants.

      The summary of the conference included the following
observations:

            "One of the reasons for calling this conference was to
      examine research needs  and consider  what should be done
      in the future.  The needs include not only specific research
      projects, but questions of surveys or  reorientation, and
      legislative programs"

      The summarizer continued:

            "It seems to me one of the papers pointed out that a
      survey program,  based on analytical determinations directed
      toward specific safety questions and dealing with specific
      organic contaminants, has much greater value than one di-
      rected to the determination of organics in general or  to
      classes of compounds.  It is rather generally true,  and I
      think this has become evident in the session on organics,

                                  1

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       that you cannot judge the physiological effect solely on the
       basis of the class of compounds to which a chemical belongs.
       This applies whether one is concerned with carcinogens or
       other kinds of toxicity.  Accordingly, there must be a close
       orientation and integration between the survey program and
       the physiological studies. "

       The person who made those statements in I960 is our keynote
 speaker - Dr. Norton Nelson.

       The next event I would like to mention is my  contact with  the
 program officer of the then National Environmental Health Sciences
 Center.  To put  it simply and bluntly,  top management of NEHSC was
 somewhat embarrassed in not having data with which to answer ques-
 tions from the "Hill" about problems which were appearing in the
 press and journals.  Staff were asked to take steps to develop some
 methodology for flagging these potential problems in  advance.   The
 result was a study undertaken by Battelle to develop a system to main-
 tain an active overview of chemical contaminants as they move  in the
 market-place.  To test out the  system, we were asked to examine (in
 a retrospective sort of way) the contamination potentials of mercury,
 vanadium, nickel, fluorocarbons, and pulp and paper production.   This
 was a preliminary cut and was not followed up.  I would like to  point
 out two significant aspects of this study.  One of the problem areas we
 studied was mercury.  The data pointed out that significant amounts
 of mercury were being "lost" in the  environment and, as  a result,
 mercury residue contamination could be expected to be found in food
 and water.  Although this observation was made in 1967,  mercury
 contamination was not considered seriously until at least 3 years
 later, when residues were detected throughout the  U.  S. and Canada.
 Thus, early-warning systems are useless if they go unheeded.

      Secondly, we made available some data in the "system" on
 thalidomide to some toxicologists, and  it was their conclusion that if
 this information  had been examined by some astute toxicologists,  it
 might have been.possible to  identify  the thalidomide problem 2 years
 in advance of its having been removed from the market.

      The  closest to a follow-up to this study was one made for the
 Consumer Protection and Environmental Health Service.   In this case,
 the person concerned with the CEPHS R&D effort was .faced with the
problem of establishing some mechanism for setting priorities  among
problem areas in order to better allocate limited R&D funds among
the various categorical programs.  Dr. Morrison will be talking more
about this later.

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      There are two other early-warning-type activities worthy of
mention.  One is the National Environmental Protection Act (NEPA).
In my opinion, this effort to look at environmental impact of projects
has been only partially successful. On the positive side,  it has forced
something to be  done but, on the negative side, ndt all assessments
are being taken seriously, so that the effectiveness of the results is
questionable.  Another factor is that  conservationists have been ini-
tiating what,  in my opinion, have been unrealistic legal actions which
are forcing court rulings that may tend to weaken the Act.

      Another is technology assessment.  For about 5 years, there
has been a great deal of  attention focused on this  subject,  culminating
in the passage of Public  Law 92-484,  setting up a Technology Assess-
ment Office,  which is just getting under way.  The verbiage which
preceded passage of the  Act is interesting, in that it gives some indi-
cations how some people view technology assessment. It is looked
upon as:

           "... a mixture of early-warning signals and visions of
      opportunity. "

           ". . . scrutinizing the interactions,  side effects, by-
      products,  spillovers and tradeoffs among several develop-
      ing technologies or between a new technology and society
      at large and the  environment. "

           "... a devicejfor winning public acceptance of techno-
      logical change and for improving the quality of information
      available to decision makers. "

           "... a means by which information now available can
      be used to increase the perception, foresight, and wisdom
      of decision makers rather than a process for decision
      optimization. "

           "... a first fumbling attempt by members of the sci-
      entific  meritocracy to engage themselves in the political
      process,  and .unreal search for metaphysical values, or
      merely a device for shaking up the status quo. "

           ". . . the need for some type of early warning  device
      which would trigger a systematic and deliberate evaluation
      of both the benefits and costs of technological change. "

      What actually will be done, only time will tell.

                                  3

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      With regard to this symposium, I do believe there is an oppor-
tunity to lay the groundwork for an early-warning-type system which
may help further past efforts and provide guidance to clarify goals and
objectives of related activities being undertaken through NEPA and,
soon, the Technology Assessment Office.  Also,  not to be forgotten,
are the provisions of the Toxic Substances legislation pending in the .
Congress,  which will require EPA to publish a list of chemicals that
may be dangerous to "health or environment".

      Lastly,  to be effective, the results of any symposium or con-
ference must have some credibility with the scientific community.  I
am sure this will be no problem,  considering the caliber of the speak-
ers on the program and, most important, the fact that the symposium
is cosponsored by EPA, NSF, and NIEHS.

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              EARLY-WARNING SYSTEM FOR TOXIC
             SUBSTANCES:  HUMAN HEALTH ASPECTS

                         Anthony V. Colucci
                         Paul E.  Brubaker
                  Environmental Protection Avency
               National Environmental Research Center
               Research Triangle Park, North Carolina
                            ABSTRACT
      The design of any early-warning testing system to assess the
effects of environmental pollutants on living systems should have as
one of its primary goals, studies of the human health effects.  This
goal has been approached from many directions and is the subject of
continuing research and controversy.

      Studies in humans are the most difficult to perform not only be-
cause of the obvious ethical and legal problems, but also because as a
group human populations are more heterogenous, mobile, and be-
haviorly complex.  Clearly, what is needed in any early warning sys-
tem aimed at assessment of impact on human health,  is a multidisci-
plinary approach encompassing clinical medicine and epidemiology
supported by adequate environmental monitoring, biochemical, and
physiological research programs.

      This discussion will focus on the current state of the art in each
of these  areas and suggest, based on previous results, the utility of
such an approach as well as suggestions for its further development.

      This topic of discussion includes those programs within EPA
such as:  Community Health and Environmental Surveillance System
(CHESS), Clinical Laboratory Evaluation and Assessment of Noxious
Substances (CLEANS),  Assessment of Cellular Toxicity and Interac-
tions of Noxious Substances (ACTIONS), Community Pesticide Studies,
National Environmental Banking System (NEBS),  and the programs of
Department of Health, Education and Welfare (DHEW), National Insti-
tute of Occupational Safety and Health (NIOSH), National Institute of
Environmental Health Sciences  (NIEHS),  Food  and Drug Administra-
tion (FDA)., and other groups as well.

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                  PRELIMINARY CONSIDERATIONS
       There are a few preliminary considerations regarding national
 health that need to be addressed prior to addressing the human health
 aspects of an early-warning system relative to toxic substances. A
 few selected indices of the health status of the American public are
 not only alarming but aid in placing the magnitude and scope of early
 warning systems in perspective.  Consider the following comments
 that can be found not only in the lay press but scientific literature as
 well.  The life expectance of our American male population has not
 substantially increased since  1948.  There  are 26 million Americans
 suffering from malnutrition who constitute a rather large segment of
 the population which is more susceptible to enhanced environmental
 stress.  Other susceptible subgroups of the population that are not in-
 cluded in this figure are children and those people predisposed by pre-
 existing overt  illness,  age, pregnancy and genetic deficiencies.  In
 accord with fundamental biological laws and theories, a deteriorating
 environment influences the reproductive capability of a given species.
 There were approximately 22  infant fatalities per 1000 live births
 during 1970 alone.  Furthermore, estimates indicate that one out of
 every 130 conceptions  ends before-the female realizes she is pregnant.
 Approximately, 25 percent of  all conceptions fail to reach an age such
 that they can survive the womb.  In addition, it is important to realize
 that 5 out of every 100 live births are handicapped by genetic anoma-
 lies.  The question regarding  the significance of these considerations
 can be partially evaluated by inspecting the number of hospitals,
 available hospital beds, the number of patients admitted and operating
 cost expended.  In 1947 there  were 6173 hospitals with 1.4 million
 beds that admitted 17. 8 million patients.  In 20 years the number of
 hospitals has increased by 15. 6 percent and the number of beds by
 21.4 percent while the number of patients rose 68. 0 percent.  In the
 same time frame,  annual operating costs increased 693 percent from
 2.4 billion (132. 35/patient) to 19 billion dollars ($638. 3/patient).  This
 cost analysis does  not  consider losses from the work force and manu-
 facturing output, the impact of permanent disabilities subsidized by
 medicare programs, inflationary adjustments, or population modes.

      Mortality and longevity are important considerations in evalu-
 ating population vitality.  At the present time American male longevity
 ranks  17th among the nations of the world, infant mortality, 16th;
while fetal death stands at 24th.

      It is  perhaps an understatement with respect to the above consid-
erations  to stress the need for an early-warning system.  However, it

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is of primary importance to clearly state the objective of such a sys-
tem; to consider the success of various preventative medical pro-
cedures that have addressed the objective,  and to evaluate these sys-
tems with specific consideration given to the environmental substances.
            OBJECTIVES OF EARLY-WARNING SYSTEM
                FROM HUMAN HEALTH VIEWPOINT
      In terms of human health, the principal objective of an early-
warning system is to detect asymptomatic, preclinical disorders, as
well as overt diseases, in early stages of subacute pathogenesis,  and
to promote environmental and medical management of associated fac-
tors in order to prevent the onset of acute pathology requiring hospital
care.  Further, attention must be given to the definition of health and
essential factors required to accomplish this objective.  Health, as
defined by the World Health Organization, is a state of complete phys-
ical, mental,  and social well-being and not merely the absence  of
disease or infirmity.  In order to accomplish the objective, effort
must be made to separate the healthy  from the unhealthy, to diagnose
the observed disorders and to have  confirmative follow-up examina-
tions with subsequent treatment in order to reduce hospital admissions
and hospital residence time.  In order to maintain an effective preven-
tion program, the etiology of the disorder must be addressed with ap-
propriate environmental monitoring,  sustained periodic  medical ex-
aminations, and epidemiology with continued refinement of existing
procedures through  aligned integrated toxicological and clinical re-
search programs.

      Screening is the systematic evaluation of a population to dis-
tinguish healthy from unhealthy individuals.  To be specific, it  is the
presumptive identification of unrecognized early disease states
through application tests and examinations.  It is  an aspect of chronic
disease control without which diagnosis, follow-up examinations, and
treatment become wasteful expenditures of valuable medical-care
resources.  In recent years a number of multiphasic screening tech-
niques have been employed by a number of federal,  state,  and indus-
trial organizations.'

      Let us review several of these systems currently  in existence
and discuss their present utility  as  well as how they can be incorpo-
rated into an effective early-warning  system.

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      Epidemiological and clinical studies in both Government and in-
dustry, such as EPA-CHESS  (Community Health  and Environmental
Surveillance System) and Community Pesticides Studies, CLEANS
(Clinical Laboratory Evaluation and Assessment  of Noxious Sub-
stances),  NIOSH (National Institute of Occupational Safety and Health),
AEC (Atomic Energy Commission), have many factors in common.-
These programs are a combination of environmental monitoring for
toxic materials and studies of morbidity and mortality patterns in ex-
posed populations at large and in human volunteer groups.   Currently
these programs are used to predict changes in trends of existing pol-
lutants, but they could be expanded into an early  warning system by
broadening the scope of pollutant monitoring and  exposure and by  im-
proving health  information gathering.

      Examples of improvements  in health-information gathering  in-
clude development of biochemical, physiological, and behavioral indi-
cators that could be measured in populations and would indicate early
preclinical disorders.  Examples of such systems currently being
developed include:

      1.  The use of gas chromatographic analysis  of urine  spe-
         cimens to detect metabolites  of potentially harmful
         compounds such as  organophosphorus pesticides,  etc.

     2.  The use of gas chromatographic analysis  of urine  to
         detect changes in the profile of metabolites which  are
         controlled by liver microsomes.

     3.  The use of selected blood and urine enzymes which are
         not pollutant specific but which predict  early changes
         in critical organ metabolism.  Example:  ornithine-
         citruline,  glutaryl transcarbamylase, serum glutamic
         oxaloacetic transaminare, alkaline phosphotase.

     4.  The use of placental enzyme activity profiles to indi-
         cate possible pollutant stress on both mother and fetus
         and thus serve as an early warning of possible  predis-
         position to disease.  These enzymes can be more  pol-
         lutant specific, for example,  palmityl transferase,
         sulfitase, isocitric dehydrogenase, G-6P dehydrogenase
         or pollutant specific enzymes such as BaP hydroxylase,
         superoxide dismutase, and carbonic anhydrase.

     5.  The use of human leucocyte enzyme systems to predict
         early  changes  in biochemical parameters such  as

                                  8

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         nucleic acid synthesis,  fatty acid metabolism, glucose
         metabolism,  protein synthesis, along with cytologic
         changes such as chromosomal aberrations, etc.

      6.  The use of changes in endogenous antioxidants such as
         Vitamins E and C to detect early damage by oxidizing
         compounds such as nitrogen dioxide and ozone.

      7.  Studies of pulmonary function using field spirometric
         techniques.

      8.  Studies of the growth of lung function in children.

      9.  Studies of changes in tolerance to work  stress in
         patients with known cardiac disorders.

     10.  Studies of EEG and behavioral changes in response to
         pollutant stress.  One example of this is the appear-
         ance of these changes induced by carbamates prior to
         its  detection in the blood.

     11.  Changes in reproductive patterns in human populations.

      One prototype of an early-warning system is the integrated sys-
tem being developed by the Kaiser Permente Program currently
operative in five western states.  This system employs an average
of 15  basic procedures.  Initially an individual is registered and in-
formation is  obtained regarding his environment.  An appointment is
then scheduled for the remainder of the study that encompasses nearly
a three-hour period. Physiological, psychological, chemical-
biochemical and socioeconomic  data are gathered,  submitted to com-
puters for organization, reduction and summary  reports.  Electro-
car diographic, chest X-rays, blood pressure,  pulse rate, visual.
acuity, hearing,  lung function, height, weight, etc.,  are among the
various testing parameters employed.   All women over 47 undergo
mammiographic studies for cancer.  Blood and urine samples are
taken from each individual for 17 routine clinical tests processed by
automated chemical analyzers to assess levels of normal body chem-
icals  (e.g., protein, cholesterol,  uric acid, and calcium).  White
blood cell, hemoglobin,  rheumatic factor, and venereal disease
analysis  are  also performed on collected blood samples.  Following
completion of these procedures each individual is given a self-
administered medical and psychological questionnaire containing 360
items designed to provide some  information pertaining to the biolog-
ical and psychological factors associated  with human health with

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 indirect information regarding the individual's environment.   In 1969
 the cost of this service was $21. 32 per individual excluding physician
 and paramedical services.  At this point it is important to realize
 that a screening program is only the laboratory facet of the complete
 health analysis.  Identical results  on two individuals can mean differ-
 ences in diagnostic procedure due  to individual variation in physiology.
 Therefore, it is important to realize the distinction between  screening
 and diagnosis,  that can only be done by physicians,  requires  other  re-
 maining relevant information.  In other  words, apart from individual
 biological or physiological variation, people are human beings, each
 with unique social, psychological and cultural imperatives that are
 important and often determining factors in their  state of health.

      There are some primary important considerations relevant to
 the successful operation of such a  screening program.  Among these
 are public  relations management,   facility location,  margin of error,
 nutritional status and variation, reliability of screening methods and
 equipment, progressive obsolescence in existing instruments,  pro-
 cedures and protocols. In existing systems over 50 percent  of the  in-
 dividuals screened are going to be unnecessarily frightened by false
 positives.  Increased financial burden is enhanced through subsequent
 evaluation of these false positives  as well as false negatives  that later
 appear as hospital admissions.  There are a variety of error sources
 in multiphasic automated screening programs  as outlined above.  Sta-
 tistical considerations alone provide some insight in probabilities and
 confidence  limits.  If normal limits are defined by the central 95 per-
 cent of the  results obtained, the probability that a normal individual
 will be  abnormal on any one determination is 0. 05 or one in 20.  If 12
 different determinations are made  on a normal individual or  the prob-
 ability of having all of the tests fall in the normal range is 0. 95,  only
 54  percent  of a healthy population  would have a completely normal
 profile.  Therefore,  as the number of tests increases, the probability
 of false positives increases.  Furthermore, it must be remembered
 that an  abnormal result is not synonymous with disease or impending
 pathology.

      Imposed upon these factors is the fact that most of the  labora-
 tory and other data on human physiology comes from a rather sparse
 population of healthy individuals that have volunteered to undergo ex-
 amination,  i.e., medical students, military personnel, prison in-
mates,  etc.  Other data on human physiology is derived from the case
histories and bodies of sick people. It must also  be realized that ex-
cept for incidence of certain communicable diseases that must be re-
ported,  the health  records of all private and public  hospital patients
                                  10

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are private and confidential.  Therefore, access to relevant informa-
tion can be a problem.  There are means of obtaining information
through appropriate legal caveats by various epidemiological pro-
grams.  However,  inspection of birth  and death certificates are often
vague and of  little use in evaluating  population health trends.

      Despite these problem areas there has been successful research
using multiphasic screening techniques.  In 1965 the annual hospital -
ization admission rate for Northern California members of the Kaiser
health program was 80 admissions per 1000 members while the na-
tional level was  137. 9 per 1000 people.  Residence time in hospitals
was reduced  by half:  532 days for Kaiser Plan members as compared
to 1061 days  per  1000 sick people as a national level.   This impressive
record was accomplished largely without the use of automated elec-
tronic hardware.  Since  1964, the Kaiser centers have introduced auto-
mated clinical chemistry instrumentation and data processing equip-
ment.  Needless  to say,  the impact  of automation, while initially
expensive, refines the efficiency of  data collection processing con-
comitant with reduced paramedical  personnel.  The use of automated
clinical laboratory test procedures  has been successful not only in
the United States but in other countries as well.  In Canada, the re-
sults of 32 tests on body-fluid samples obtained from 1010 randomly
selected volunteer outpatients indicated some 430 individuals with un-
expected abnormal results, notably, within statistical probability.
Upon further consultation, 253 of these individuals declined further
examination  and testing;  only 95  of the remaining 177 agreed and
actually participated in follow-up examination. The result of the
follow-up exams  revealed^S percent of the 95 with subclinical dis-
orders that include diabetes,  urinary-tract anomalies, and liver,
lung,  thyroid, and blood disorders.  In Sweden,  35 chemical labora-
tory determinations performed on 995 apparently healthy randomly
selected 45-65 year old individuals  revealed a 30.4 percent incidence
of disorders  ranging from cancer to bacteruria in males with a 53. 0
percent incidence in women.  The net result of mechanization is the
obvious impact on cost in that many tests can  be done for the price of
a few.  Furthermore, professional  time, retesting frequency,  and
unnecessary  treatment tends to be minimized  with reduced patient
anxiety.  All of these studies indicate that  early warning systems  of
this type are useful and can be applied in a practical manner.

      Emerging on the horizon is still another system which should
prove most useful as an early-warning  system.  Reference is made to
the NEBS (National Environmental Banking System) which this year is
getting under way through the cooperative  efforts of the Environmental
Protection Agency,  National Science Foundation, Oak Ridge National

                                 11

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 Laboratory, and National Bureau of Standards.  In addition since
 Japan, Sweden, Belgium, and Spain have agreed to participate, the
 NEBS will hopefully be global in scope.  In this system samples of
 tissue from humans and other biota along with specimens of environ-
 mental media  such as air, water,  soil and food will be preserved,"
 stored,  cataloged  and selectively analyzed for pollutants.

       The system  will not only provide flashback capability in the
 event new problems emerge, but will also provide a predictive func-
 tion by having a broad scope of chemical analyses with documented
 changes in accumulation of potentially harmful pollutants that can be
 used to detect problems very early and forecast future problem areas.

       Another area of need is the development of rapid in vitro screen-
 ing systems for toxic substances which are more predictive than
 present systems and have valid extrapolatability to man.  We would
 not attempt to review the  myriad types of systems which have been
 proposed to date but it can be safely said that each has its own inade-
 quacies.  These inadequacies stem largely from the obvious difficulty
 in extrapolation of animal data to man compounded by the jump from.
 all isolated preparation to any in vtvo system.

       Still, if we will pay the price, these systems can be constructed
 and ultimately give credibility and legal sanction.  Unfortunately no
 one group or combination of groups has had the unique insight or re-
 sources to pursue  in a logical progression enough compounds from
 m vitro to in vivo mouse and man to establish a predictive system.

       Future attention must be focused in this area of need and em-
 phasis placed on the chemical structure biological activity relation-
 ship throughout. Clearly not every potentially harmful compound can
 be screened.  Therefore a body of knowledge regarding toxicity of
 chemical structures has to be accumulated.  To date such information
 is accumulated either in retrospect (as with  drugs) or by chance (such
 as with chlorinated hydrocarbons) but this approach will not suffice
 for the future.

      In conclusion, it should be stated that what we have presented
 is only a brief overview of the current state  of the art and we are sure
many programs have not been discussed.  Similarly, no attempt was
made to outline the myriad needs in environmental monitoring and
 analysis upon which any early-warning system depends.  Hopefully,
throughout this conference,  all these needs will be addressed and re-
addressed such that a new program with new approaches will emerge
based  on collective mutual interest  and begin to solidify into a useful
early-warning  system for toxic substances.
                                 12

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LANDSCAPE GEOCHEMISTRY AND ENVIRONMENTAL PROBLEMS
                      John A. C. Fortescue
                Department of Geological Sciences
                Brock University, St.  Catharines,
                         Ontario,  Canada
                           ABSTRACT
      Geochemistry is a scientific discipline which is concerned with
the role of all elements in the synthesis and decomposition of natural
materials located at, or near, the daylight surface of the Earth.
Landscape Geochemistry is that part of geochemistry concerned with
the synthesis and decomposition of natural materials as a result of
the interaction of the Lithosphere with the Hydrosphere,  Atmosphere
and Biosphere.   The  need for a holistic approach to  the design of
"Early-Warning  Systems for Toxic Substances" is often expressed
and the purpose of this paper is to relate this need to research already
completed in the fundamental and applied aspects of  the Landscape
Geochemistry approach.   Five examples of research projects of this
type will be described briefly and at the end of the paper some con-
clusions will be drawn regarding the feasibility of the approach in
relation to the theme of the seminar.
                         INTRODUCTION
      Our topic today is early-warning systems for toxic> substances
which have  been added to the environment.  From the viewpoint of geo-
chemistry the addition of such substances to the environment is
essentially  an act which modifies the natural circulation of chemical
substances  between the different components of the systems which
occur at, or near, the daylight surface of the Earth.   The geochemist
stresses the natural circulation patterns of elements  which can be
used as  a basis for the detection of imbalances harmful to man
caused by the short, or long, term application of toxic substances to
the environment.
                                 13

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      In order to  stress the holistic aspects of the geochemical
 approach to environmental problems as clearly and briefly as
 possible, it is convenient to refer to three levels of thinking at which
 the geochemistry of the environment is considered.  These  are the
 "grand strategic level",  which includes broad generalizations upon
 which geochemistry is based;  the "strategic level", which in this
 case involves the concepts associated with landscape geochemistry;
 and the "tactical level",  which is concerned with the description of
 examples of the application of the landscape geochemistry approach to
 the solution of specific environmental problems.
                   WHAT IS GEOCHEMISTRY?
      Geochemistry is the scientific discipline which is concerned
with the role each element in the Periodic Table plays in the synthesis
and decomposition of natural materials of all kinds.  The "Grand
Strategy" of Geochemistry is epitomized by the concept of the Geo-
chemical Cycle (Figure  1) which is seen to be in two parts - a Major
Cycle,  which is essentially geological, and  occurs within the Earthrs
crust; and a Minor Cycle, which occurs where the  Lithosphere,
Hydrosphere, Atmosphere, and Biosphere interact forming the
weathering crust of the Earth.  In this paper we are only concerned
with the Minor Geochemical Cycle.  It should be noted that, for a
given element, the Liberation,  Transport and Incorporation stages of
the Minor Geochemical Cycle may not be completed in practice be-
cause at some  stage the cycle may be halted indefinitely, short
circuited or even have its direction reversed.  But in spite  of these
limitations  the concept of the Geochemical Cycle,  when it is com-
bined with the notion of the natural abundance of chemical elements,
provides a useful overview of geochemistry which may be used as a
starting point for a discussion of landscape  geochemistry.  Further
information on general geochemistry may be obtained from  the books
by Clarke (1924), Rankama and Sahama (1950), Goldschmidt (1954),
Mason (1966), Wedepohl (1970),  and Fairbridge (1972).
                                 14

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                           GEOCHEMICAL
                            .TRANSPORT'
                         *•) ATMOSPHERE \
                                          BIOSPHERE
                            HYDROSPHERE f
            EARTH'S SURFACE V
BIOGENETIC
    >S
    X
                            LITHOSPHERE
                   CRYSTALLINE
                      ROCKS
                                    METAMORPHISM
                         PRIMARY MATERIAL
             FIGURE  1.  THE GEOCHEMICAL CYCLE
                         [Modified from Mason (1958)]
             WHAT IS LANDSCAPE GEOCHEMISTRY?
      A simple definition of landscape geochemistry is "the study of
the role chemical elements play in the synthesis and decomposition of
natural materials which occurs at, or near, the daylight surface of
the Earth under a given set of climatic constraints during geological
time".  Landscapes are said to be made up of a number of component

                                  15   "

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parts (eg. rocks, soils,  plants, animals, etc. ) which chemically
interact with each other resulting in the circulation of chemical
elements through them.  Strictly speaking, all landscapes may be
related to four generalized conceptual models which were described
many years  ago by the Pioneer Russian geochemist B.  B. Poiynov
(Glazovskaya 1963)  as the "Elementary Landscape Types".  Because
of the complexity of landscapes it is often advisable to refer to them
by block diagrams instead of describing them in words.   On Figure
2 the four elementary landscape types are illustrated in this way by
means of "prisms"  extending from the unweathered bedrock to the
atmosphere. Briefly, terrestrial landscapes are of two types:  eluvial
      Saline Soil
      ILUVIAL
      LANDSCAPE
Podzol Soil
ELUVIAL
LANDSCAPE
Organic Soil
SUPER-AOUAL
LANDSCAPE
Lake
AOUAL
LANDSCAPE
     FIGURE 2.  FOUR ELEMENTARY LANDSCAPE TYPES

                 [From Fortescue and Bradshaw (1973)]
                                16

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 landscapes where the annual precipitation exceeds the evaporation
 and illuvial landscapes where the reverse is the case.  In cases where
 the daylight surface and  the water table are coincident (i.e.,  in a
 marsh or  bog),  a "super aqual landscape" is found,  and in a lake
 where  the  surface of the lithosphere is covered by a layer of water,
 a "subaqual" landscape is  found.

        One  may well ask  "What has all this to do with early-warning
 systems for toxic materials?"  The answer to this question lies in
 the information obtained from tactical-level examples of landscape
 geochemistry carried out in the real world.  But before these are
 described  it is necessary to indicate briefly the present state of the
 art of landscape geochemistry.  In Figure 3,  a flow diagram is given
Practical Applications:
    Pollution

Studies of man's effect
on the total chemistry
of the environment
 Examples: JLake Sediment
          Core Project,
          Ontario
         Stream Sediment
          Surveys,
       1   St. Catharines
                            General Landscape Geochemistry
                                    Objective
                           To obtain mathematical models of
                           landscapes by means of which the
                           behaviour of chemical elements
                           within them can be predicted
                           accurately
                            Examples: The Dorset Project
                                    The Chalk River Project
Practical Applications:
   Nutrition

Study of relationships
between geochemistry
and the health of plants
animals and/or man
 Example:
Regional Stream
 Sediment Surveys,
 Eire
Practical Applications:
   Ore Prospecting

Studies of natural
geochemical anomalies
caused by ore deposits
in landscapes
 Examples: Described in books
          by Hawkes and Webb
          (1962), Cameron (1966),
          Boyle (19701, Kvalheim
          (1967)
      FIGURE 3.   THE SCOPE  OF LANDSCAPE  GEOCHEMISTRY
                                        17

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         LOCATION OF INDIVIDUALS OF
                       5 TREE SPECIES
            LEVEL FOREST
          12345
         A x
 x
*xA x
    2OOM
                SLOPE FOREST     BOO    LAKE
               6  7  8  9  10
                I-
          -200M
          60OM
                                               *•
                                               IOOM-.
                                                     g
                          PLAN VIEW
                         I
                         !   TRANS-    |
                         I  ELUVIAL   ! SUPER
GENERALISED  LANDSCAPE SECTION : CONCEPTUAL MODEL
               DORSET PROJECT (diagram)
FIGURE 4.
CONCEPTUAL MODEL OF A FORESTED LANDSCAPE
SECTION AND A SCALE DRAWING OF THE DORSET
SECTION [From Fortescue, et al. (1973)]
                           18

-------
which indicates the potential scope of landscape geochemistry which
involves practical as well as theoretical research.  This flow diagram
was included in order to focus attention upon the need to consider
early-warning systems for toxic materials in relation to both the
strategy and the tactics of the  scientific discipline.   The study of
trace substances in the environment has, up to now, frequently lacked
an intellectual superstructure  at the strategic  level of thinking.  Con-
sequently, much research time and money has been spent on projects
which are essentially "isolated incidents" which cannot be directly
related to any discipline. Let us hope  that close attention will be
paid to this point when scientists design early-warning  systems for
toxic materials.  One way to promote such thinking is to offer a  set
of guidelines for the design of experiments which will be subject to
review after a given period of time long enough for  practical results
to be obtained.
            Examples of "Tactical Level" Investigations
                   in Landscape Geochemistry
Example 1.  A preliminary study of a forested
landscape section at Dorset, Ontario
      In June and July, 1972, a preliminary experiment was carried
out at a specially selected landscape site on a forested hillside site
located near Dorset, Ontario [ Fortescue, et al.  (1973)].  Very
briefly, the site was selected for study on the basis of the con-
ceptual model of a forested hillside shown in Figure 4 and includes
a "transeluvial landscape." on a hillside adjacent to a "super-aqual
landscape" located in a bog.  Distribution patterns for a macronutri-
ent (magnesium) four micronutrients (manganese, iron, copper,
zinc),  and two nonnutrient elements (aluminium and lead) were
obtained from samples of -80 mesh soil material and  tree branches
taken at intervals of some 20M along the 400M section.  We are con-
cerned here only with the distribution patterns obtained for Aluminium
and Lead  (Figures 5 and 6).
                                 19

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                       2SO|
ts>
O
           250
                                                                                                LANDSCAPE  SECTION
                                                                                                        NEAR
                                                                                                  DORSET, ONTARIO
                                          DATA FROM YELLOW BIRCH

                                                             250


II 1
                                            Distribution patterns for
ALUMINIUM
                                                                                  /'
                                                                                  / >
                                                               DATA FROM BALSAM FIR
                                   DATA FROM MAPLE


1 1
. 1

1







f
r

                                                                                   DATA FROM BLACK SPRUCE
                                     MINERAL  SOIL PROFILE DATA
                                                                                            ORGANIC SOIL PROFILE DATA
              SCALE FOR CONTENT OF ALUMINIUM
                        H SOILS
              ALUMINIUM (MINERAL) A - B  0 -I5OO PPM
              ALUMINIUM (ORGANIC) C-D  0-30OOPPM


                             FIGURE 5.
                 TOPOGRAPHIC  SECTION
    OVERSTORY DATA FROM BRANCHES (PPM OVEN DRY WEIGHT)
    MINERAL SOIL (PPM COLD HCI ON -80 MESH OVEN DRY MATERIAL)


LANDSCAPE SECTION NEAR DORSET, ONTARIO

DISTRIBUTION PATTERNS FOR ALUMINIUM

-------
            40
                 I  I
4O
                                DATA FROM YELLOW BIRCH
                                                     40
                                                     „    1111    I
                                                      DATA FROM BALSAM FIR
                                                       LANDSCAPE SECTION
                                                                NEAR
                                                          DORSET. ONTARIO

                                                Distribution  patterns for  LEAD
1 1 1 1
1 II II 1
                        DATA FROM MAPLE
                                         DATA FROM BLACK SPRUCE
                          MINERAL SOIL PROFILE DATA
                                                                                    ORGANIC SOIL PROFILE DATA
 SCALE FOR CONTENT OF LEAD
         M SOILS
 LEAD (MINERAL) A-B   0-IS PPM
 LEAD (ORGANIC) C-D   0-300 PPM
                FIGURE 6.
                                                    TOPOGRAPHIC  SECTION
     OVERSTORY DATA FROM BRANCHES (PPM OVEN DRY WEIGHT)
     MINERAL SOIL (PPM COLD HCI ON -so MESH OVEN DRY MATERIAL)

LANDSCAPE SECTION NEAR DORSET,  ONTARIO
DISTRIBUTION PATTERNS FOR LEAD

-------
       Several points of interest regarding the natural distribution of
 these two elements in the plants and soils at Dorset are evident from
 the diagrams.  The vertical distribution of aluminium is quite
 different in the mineral soil compared with the organic soil and there
 is no surface enrichment of the element in either of the soil types.
 The content of aluminium in the deciduous tree branches is con-
 sistently less compared with that in the coniferous  species, and,
 in the Black Spruce there appears to be an increase in the content
 of the element in trees growing away from the bog margin.

       The distribution of lead in the soils differs from that for
 aluminum because lead is accumulated — by the so-called "Gold-
 schmidt Enrichment" —  in the organic layers of the mineral soil and
 at the surface of the bog. More lead was found in the branches of
 the coniferous trees compared with the deciduous species and the
 amount of lead also tended to increase towards the  center of the bog
 in the Black Spruce trees.

       We can conclude from this preliminary experiment that
 chemical elements behave differently within the same  landscape
 type as distribution patterns vary from element to element according
 to their amount, distribution and chemical behaviour within the soil.
 It was also evident that different tree species growing on the same
 soil take  up different amounts of chemical elements - using an oven
 dry weight of branch material as a basis for  comparison.   [ (For
 further details see Fortescue,  et al. (1973).]

       Tactical-level experiments of this type may conveniently be
 related to strategic-level and grand-strategic-level thinking.   From
 the strategic-level viewpoint the Dorset project is interpreted to
 indicate that characteristic  distribution patterns for particular
 elements can be easily described in soils and plants taken from
 different landscape types which lie adjacent  to one another. Varia-
 tions in distribution patterns at one, or more,  of a  series  of sites
 studied in this manner might be a valuable early warning system re-
 lating to modifications of the environment by chemical substances  -
 for example added to the landscape  in rain.  From the viewpoint of
 grand strategy, studies of the type carried out at Dorset could be
 expanded  to  include not seven but all elements in the Periodic Table
 and not just  in Ontario forests but all suitable types of forest.  It
 seems clear that one contribution this type of study could  make
would be to provide base line information on the distribution of all
elements  (not just nutrients) in forests which could be used to detect
modifications of the chemistry of the environment at an early stage
in areas where this was suspected.

                                 22

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Example II.  A preliminary investigation of a
forest stand at Chalk River,  Ontario
      The trees growing at Dorset had grown normally for a period
of at least ten years prior to sampling.  But what happens to trees
when their growth rate is reduced, or  increased, by environmental
changes?  A preliminary experiment along these lines was carried
out in an Aspen (Populus tremuloides and P. grandidentata) stand
located at Chalk River,  Ontario [ Fortescue (1973a)] .  Briefly, sub-
samples of branch material representing lead shoot elongation for
each year of a ten-year period  (from I960 to 1969) were  obtained from
twelve individuals of each of three species (P. tremuloides,
P. grandidentata, and Betula papyrifera). Each tree was close to
being 50 years  old.  The object of the experiment was to discover
the effect on the uptake of the micronutrient elements  copper and
zinc and the trace elements lead and nickel of changes in the growth
rate of the popular trees brought about by an attack by the forest
tent caterpillar (Malacosoma disstria Hon.) during the growing
seasons  of 1962, 1963, 1964, and 1965.  The birch trees were not
affected  and used as controls.

      The information obtained from this experiment is  summarized
in Figure 7 where the dotted lines at the bottom  of the graphs  indicate
   4OQOO
       I960 61 62 63 64 66 66 67 68 69  I960 61 62 63 64 69 66 67 68 69 I960 61 62 63 64 69 66 67 68 69
               AGE OF
            BRANCH SU6SAMPUE
    AGE OF
BRANCH SUBSAMPLE
    AGE OF
BRANCH SUBSAMPLE
       ATW-Avtrage Twig Weight (g)      — - Mieronutritnt Eltmtnt (Ports Per Million. Oven Dry Wright)
       CRI -Cumulative Radial Increment (cm) — - Non-Nutrient Element (Parts Per Million-. Oven Dry Weight)
   FIGURE 7.  ESTIMATES FOR THE ELEMENT STATUS OF POPULUS TREMULOIDES. POPULUS
            GRANDIDENTATA AND BETULA PAPYRIFERA FROM THE PERCH LAKE ASPEN
            STAND, CHALK RIVER, ONTARIO, CANADA
            [From Fortescue (1973a)]
                                   £* j

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 the growth rate of tree boles (cumulative radial increment) and
 branches (average branch subsample weight).  The full lines in-
 dicate the concentration of each of the four elements in the branches
 over the 10-year period.  The individuals  of P. tremuloides were
 most  affected by the insect attack which resulted in a minimum in the
 branch growth curve, associated with a maximum in the curves for
 the nonnutrient elements nickel  and lead; whereas the curves for the
 micronutrient elements copper and zinc were unaffected.

       This preliminary study indicates that nonessential trace
 elements in tree branches may be more sensitive indicators of
 changes in the chemistry of the  environment than micronutrient
 elements and that experiments of the type  described may be used as
 "history books" to describe the  effect of toxic materials on trees.
 Studies along these lines might lead to the selection of tree species
 and chemical elements which were particularly sensitive to minute
 changes in the chemistry of the  environment which could be used as
 a principle upon which to base an early-warning  system.

       This  principle has been followed up on some detail by scientists
 interested in the effects of gaseous"elements on plant growth.  It has
 been known for some time that epiphites and lichens are particularly
 sensitive indicators  of small amounts of sulphur dioxide and fluoride
 in the  atmosphere.   Further information on this  interesting approach
 to the  detection of changes  in the environment may be obtained from
 the recent book edited by Ferry, Baddeley and Hawksworth (1973).
 Example III.  The use of lake sediment cores to detect
 man's effect on the  chemistry of the environment
      It was noted that at Dorset lead accumulated in the humus layer
of the mineral soil and at the surface of the organic soil.  Further
information on the behaviour of this element in relation to man's
activities was obtained from the study of lake sediment cores from
Southern Ontario  [ Terasmae et al.  (1973)],  see Figure 8.

      When European man came to  Southern Ontario over a hundred
years ago he logged the area and cleared it for agriculture.  This
disturbance is recorded by an increase in ragweed (Ambrosia  sp.)
pollen in lake sediments laid down at that time.  Under favorable
conditions  a palynologist making an examination of a sediment core
taken from one of these lakes (e.g., Puslinch Lake Figure  9) can date
the part of the core laid down when the forested landscape was
disturbed.
                                24

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tn
                 covered  by  stream  sediment  survey

            FIGURE 8.  INDEX MAPS SHOWING LOCATION OF LAKES SAMPLED AND AREA
                        COVERED BY STREAM SEDIMENT SURVEY IN SOUTHERN ONTARIO
                        AND LOCATION OF LAKE SEDIMENT CORE SITES IN PUSLINCH
                        LAKE

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WAAA
                                                 WAAB
Depth
 Cm
  0
 20
 40
 60
 60
 IOO
     M
          % Ambrosia
  Leod.ppm  Cadmium, ppm
Q	MO 0	 5
Depth
Cm
0
20
40
60
60
100

G

G
G
V
0



% Ambrosia
16
£
jt
?
•

                                                                       Lead, ppm  Cadmium, ppm
                                                                              140 0     5
WAAC

Depth      % Ambrosia     Lead, ppm  Cadmium, ppm
 Cm      0        16  0       MO 0     5
  0
20



40



60



80



IOO
    M
    M
                                  I
                                                 WAAO

                                                 Depth      % Ambrosia     Lead, ppm Cadmium, ppm
                                                 Cm       0         16  O       MO 0     5
                                                   0
                              20



                              40



                              60



                              60



                              100
                                                      M
                                                      M
                                                      M
                                              G= Gyttja

FIGURE 9.   PHYSICAL,  PALYNOLOGICAL AND CHEMICAL DATA ON FOUR

              LAKE SEDIMENT CORES FROM PUSLINCH LAKE,  ONTARIO


              [Terasmae et al. (1973)]

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      When the ash percentage, the copper content and the lead con-
 tent in subsamples of cores is compared with the distribution pattern
 for Ambrosia sp.  pollen in the cores it is  seen (Figure 9 WAAA core)
 that lead increased in the core at the same time.  We believe
 (Fortescue 1973b) that the increase in lead is associated with the
 breakdown of the forest humus brought about by man's activities in
 the drainage basins,  although this relationship has not been worked
 out in detail.

      From the viewpoint of early-warning systems for toxic sub-
 stances, these patterns should be considered carefully because it
 may very well be that lake sediments hold a clear record of changes
 in the chemistry of a terrestial environment which can be explored
 in no other way.  More generally,  this is an example of how changes
 in the chemistry of one landscape type  (e.g. , eluvial) may be
 detected in another adjacent to it (e. g. , subaqual).
 Example IV.  The use of stream sediments to detect natural
 — and man made —variations in the chemistry of drainage basins
      During the past 20 years geochemical prospectors have
 repeatedly demonstrated [Hawkes and Webb (1962), Kvalheim (1967),
 Boyle (1971),  etc.] that mineral deposits located in drainage basins
 can be located on the basis of data obtained from the chemical
 analysis of samples of dried, sieved, stream sediment material.
 More recently, the streajm sediment approach has been used
 (Webb 1969) to detect imbalances in stream sediments associated
 with problems in agriculture.  As a result of these activities, and
 others like them,  it was decided in 1970  to make a stream sediment
 survey (suing the approach pioneered by  geochemical prospectors)
 of an area of 450 square miles around the city of St. Catharines,
 Ontario in order to discover if the information obtained from it
 could be interpreted in relation to man's effect on the  environment
 or variations  in the geology of the area.

      In Figure 10 the distribution of nickel in stream  sediments
collected from the St.  Catharines area is shown at three levels of
concentration  (Class A: over 40 ppm, Class D: 11-20 ppm, Class
E: 0-10 ppm).  The Class A results were found to be in two clusters,
one associated with an industrial plant in a rural area, and the other
near industrial plants in Thorold, immediately south of urban
St.  Catharines. The dots and circles (1105 of them) on the Class  D
map (Figure 10) indicate the sample sites from which the stream

                                 27

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sediment samples were taken.  The dots indicate the relatively
uniform distribution pattern of the most frequent concentration values.
The Class E nickel values are seen to be concentrated along the
shore of Lake Ontario and in the center of the south of the map where
a "kame" (glacial feature) is located.
 FIGURE 10.  GEOCHEMICAL MAPS OF THE AREA AROUND
              ST. CATHARINES SHOWING THE DISTRIBUTION
              OF NICKEL AND LEAD IN SAMPLES OF STREAM
              SEDIMENT MATERIAL

              [From Fortescue (1972)]
                               2.8

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      The distribution of lead in the same stream sediment samples
is shown in Figure 10.  In this case the patterns are not so well
developed as in the case of nickel.  The Class A values (over 80 ppm)
and the Class B  (61-80 ppm) values are found in the St. Catharines -
Thorold area and in the northwest of the area below the Niagara
Escarpment where they are considered to be due to residues of lead
arsenic sprays added to orchards.  Other high values, to the south
of the Niagara Escarpment (marked with an "R") are considered to
be due to lead derived from the Lockport Dolomite,  the bedrock
underlying the area.   [ (Fortescue et al. (1971).]

      In summary, the stream sediment geochemicai survey approach
may,  under favorable conditions, be used to locate environmental
variations  in trace element patterns which relate to (1) Bedrock
geology, (2) Pleistocene deposits, (3) Urban Industrial area,  (4) Rural
Industrial areas or (5) areas where trace  elements have been added
during fruit growing.  It seems clear that the stream sediment survey
approach should be seriously considered for early-warning surveys
in areas where they may be suitable.
Example V.  The use of stream sediments to locate an area
characterized by molybdenum induced copper deficiency
in cattle
      A good example of the use of stream sediments to solve a prob-
lem involving the well-being of animals was described in a series of
papers [Webb (1964), Webb and Atkinson (1965), Thornton et al.
(1966)] published some years  ago by geochemists from the Applied
Geochemistry Research Centre  at the Royal School of Mines in
London who worked in an area in Co. Limerick, Eire.   Briefly, stream
sediment reconnaissance surveys revealed an area of some 30 square
miles characterized by molybdenum and selenium anomalies  related
to an area of marine black shale.   Detailed geochemicai surveys,
based on soils and pasture herbage, showed that high molybdenum
occurred in these materials as well as in the  stream sediments,
Figure 11.   An investigation of blood copper levels in cattle grazing
in the area showed a highly significant correlation existed between
areas of high molybdenum  in the environment and areas where the
cattle suffered from low blood copper.

-------
tb) St * Mil « B-24 m )  |   |»-» [    [»-»
                                                           (o)
                                                                t   O   SO  290 >»0
                                                             Ma n tlraom wdKntnl (ppm)
                                                                                               *iti I	lAlknun
                                                                   *• n w?m%*m
                                                                    • \ J1 >"> -.••-...•.. -jf  \-»ic3L
                                                                   •o "•-' /••ryr—&*f  V:S\
                                                                   TC^	y ^r	v::.' >
                                                        (b) Mo in wil ol B-24 m (pom)  [   |<5  [ •••• J5-IS  [   ]»-48 ^-jijjjjxfl
                                                                   ' PF^/ V» ^/V '"^
                                                                   v«;i?//  ////  lii-^:i!
FIGURE 11.
                                                           (O M, „ h^oo. (ppm dr, n«mr)
                   TH2 DISTRIBUTION OF SELENIUM AND MOLYBDENUM IN STREAM

                   SEDIMENTS,  SOIL AND MIXED HERBAGE COLLECTED FROM AN

                   AREA IN  CO. LIMERICK, IRELAND

                   f Redrawn from Webb and Atkinson (1965)]

-------
      Several points of interest to the design of early warnings for
toxic substances may be pointed out in relation to this research.
First, the study indicated that relationships between (a) bedrock
geology, (b) stream sediment trace element content,  (c) pasture
soils,  (d) pasture herbage and sickness in cattle could be  established
with the minimum of effort.  Second, the study showed how the
toxic effects  in the cattle (i. e. , low blood copper) resulted from an
interaction between excess molybdenum and copper and was not
related to the level of copper in the herbage.  A third aspect of this
study was that the amount of molybdenum in the herbage was not
constant the year round but varied with season which further
complicates investigations of relationships of this type.  Clearly,  a
case can be made for the consideration of a Landscape Geochemical
approach to the solution of similar complex problems in other areas
once they are identified.
                            SUMMARY
      In this paper we have reviewed briefly aspects of the Geochem-
ical approach to the solution of environmental problems.  To begin
with it was noted that geochemistry can be studied at three levels of
thinking called here "grand strategic", "strategic", and "tactical".
In the second part of the paper five examples of environmental geo-
chemical investigations were given in order to indicate how the
Landscape Geochemical approach might be used to provide early
warning of toxic materials in the environment.  It should be  stressed
that much research along the lines described is needed before the
reliability of geochemical methods for early warning of toxic mate-
rials in the  environment can be considered established.  Such
research would be most effective if it were designed on the basis of
"strategic level" rather than "tactical level" thinking so that sets of
comparable information are collected while experience is being
gained.
                                 31

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                          CONCLUSIONS
       Scientists involved in the design of experiments in relation to
 early-warning systems for toxic materials research might consider
 the grand strategy, strategy,  and the tactics of the landscape geo-
 chemistry approach to the solution of environmental problems with
 profit so that guidelines may be established which will result in the
 collection of information packets which can be  carefully related and
 compared with each other.
                           REFERENCES
 Boyle, R. W.,  "Geochemical Exploration", C.I. M. M.  Special Volume,
 (11) (1971).

 Clarke, F. W.,  The Data of Geochemistry, Fifth Edition U. S.  Geol.
 Sur.  Bull. 77 (1924),  841 pp.

 Fairbridge,  R.  W., The Encyclopedia of Geochemistry and Environ-
 mental Sciences, Van Nostrand — Reinhold Company, New York (1972),
 1321  pp.

 Ferry, B. W.,  Baddeley, M. S., and Hawksworth, D.  L., Air
 Pollution and Lichens, Athlone  Press of the University of London
 (1973), 389 pp.

 Fortescue, J. A. C.,  "A Preliminary Study of Relationships Between
 Patterns on Topographic, Geological,  Lands Use,  and Geochemical
 Maps of the Area Around St.  Catharines, Ontario Canada", Trace
 Substances in Environmental Health, V Edition, D. D. Hemphill^
 University of Missouri (1972), pp 497-514.

 Fortescue,  J.A. C., "The Use of Branches as a Basis for the Estimation
 of the  Copper,  Zinc,  Lead and Nickel Status of a Forest Stand", Can.
 Jour. Forest Res.",  3 (1), 27-33,  (1973).

 Fortescue, J. A. C., "The Need for Conceptual Thinking in Geoepidem-
iological Research",  Trace Substances in Environmental Health, VI
Edition, "D. D. Hemphill,  University of Missouri (1973), pp 333-341.

                                 32

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Fortescue, J.A. C., Dupuis, J., Winn, R., Hughes,  J., Gawron, E.,
and Ernesaks, I.,  "A Preliminary Study of the Use of Stream Sediment
Geochemistry to Detect the Effects of Man's Activities on the Environ-
ment Around St. Catharines, Ontario", Brock University,  Dept. of
Geol.  Sciences  Research Report  No.  2 (April,  1971), 22 pp.

Fortescue, J.A. C., and  Brad shaw, P. M. B., "Landscape  Geochemistry
and Exploration Geochemistry",  Brock University, Dept. of Geol.
Sciences Research Report No.  17 (June,  1973),  66 pp.

Fortescue, J.A. C., Burger, D., Grant,  B.,  Gawron, E., and Curtis,
S., "Preliminary Landscape Geochemical Studies at Forested Sites
at Dorset, Ontario, and at Oak Ridge, Tennessee", Brock University,
Dept.  of Geol. Sciences Research Report No.  12 (February,  1973),
52 pp.

Glazovskaya, M. A.,  "On Geochemical Principles of the Classification
of Natural Landscapes" Intern. Geol. Rev., Mil) 1403-1431 (1963).

Goldschmidt, V. M.,  Geochemistry, Clarendon Press,  Oxford (1954),
730 pp.

Hawkes, H.  E., and Webb, J. S., Geochemistry in Mineral Explora-
tion, Harper and Row, New York (1962),  415 pp.

Kvalheim A., Ed.,  Geochemical Prospecting in Fennoscandia, Academic
Press (1967).

Mason,  B.,  Principles of Geochemistry, Third Edition, John Wiley,
New York (1966).

Rankama, K., and Sahama, Th. G., Geochemistry,  University of
Chicago Press (1950), 912 pp.

Terasmae J., Fortescue, J.A. C., Flint, J. J.,  Gawron, E. F.,
Winn, R. F., and Winn,  C. E.,  "Palynology and Chemistry of Lake
Sediment Cores From Southern Ontario,  Related to Man's Activities
on the Environment",  Brock University,  Dept.  of Geol.  Sciences
Research Report No.  10  (July, 1972), 160 pp.

Thornton, I., Atkinson,  W. J.,  and Webb, J.  S., "Geochemical
Reconnaissance and Bovine Hypocuprosis in Co. Limerick, Ireland",
Irish Jour. Agric. Res., 5^ 280-283 (1966).
                                 33

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Webb, J.  S.,  "Geochemistry and Life", New Scientist,  23_,  504-507
(1964).

Webb, J.  S.,  and Atkinson, W. J., "Regional Geochemical Recon-
naissance Applied to Some Agricultural Problems in Co. Limerick,
Eire", Nature, ^08, 1056-1059(1965).

Wedepohl, H., Geochemistry. Holt Rinehart Winston Inc., New York
(1970),  231 pp.
                                34

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          LEGISLATION AND LAWS CONCERNING EARLY
           WARNING SYSTEMS FOR TOXIC SUBSTANCES

                       Michael B.  Brownlee
                    Commerce Committee Staff
                           U. S. Senate
                        Washington,  D. C.
                            ABSTRACT
      The existing statutory basis for the control of the manufacture,
distribution, and disposal of toxic chemicals is reviewed.  Included are
pesticides,  drugs, food additives, cosmetics,  chemicals threatening
occupational safety,  and radioactive materials.

      Unregulated hazards are described as well as pending legislation
to deal with such hazards.   Of primary importance are the environmental
effects of a number of consumer products,  including detergents and
products containing heavy metals.

      Finally, the relevant  considerations Congress  must weigh in es-
tablishing "early-warning systems" for toxic substances are described.
Alternatives are discussed  with particular  emphasis on the "Toxic Sub-
stances Control Act  of 1973" now pending in Congress.
           INTRODUCTION AND DEFINITION OF TERMS
      As my assignment this morning is to review existing statutes and
pending legislation in the Congress dealing with early-warning systems
for toxic substances, it might be fruitful at the outset to define the
limits of my presentation and to describe some of my own limitations
with respect to defining the mgans of controlling toxic  substances.

      My work on the staff of the Committee on Commerce deals pri-
marily with assisting the Committee with science matters associated
with environmental legislation.  Although I haven't worked directly in
the field for about 4 years,  I nonetheless  still regard myself as a fish
and wildlife biologist.  I profess to less and less identification with that
occupation, however, as in recent years my function on the  Committee

                                 35

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 staff has been less in the area of scientific interpretation and more in
 the area of legislative drafting and escorting legislation through the
 Congress.

       In terms of describing my biases in helping formulate regulator/
 policy for the control of toxic substances, it should be noted here that'
 I have a very high affinity to the Senate-passed version of the Toxic
 Substances Control Act, having been associated with it since Senator
 Magnuson introduced the first version some three  years  ago on behalf
 of  the Administration.  Thus, if I seem more a cheerleader for this
 pattern of regulating the chemical substances rather than an impartial
 observer, you now-have the reasons  why.

       Obviously,  the notion of "early-warning systems" can mean a
 great many things.  Not only can it mean the extent to which regulatory
 authorities are given a look at safety data and an opportunity to control
 substances before they are put to their respective  uses,  but it can also
 encompass the  entire range of monitoring the presence of chemicals in
 the environment,  monitoring environmental indicators, the  reporting of
 chemical use by manufacturers, and a number of other techniques.
 In  order to appropriately limit this presentation, however, it is my
 intention to deal only with the means by which regulatory control is
 applied prior to the marketing of-potentially toxic chemicals.   To go
 beyond this limitation would strain not only my abilities but your
 patience as well.

      In doing so,  it would seem appropriate to give a brief description
 of the types of premarket review now applied to a variety of chemicals
 which could be termed "toxic chemicals" and to review as well proposals
 for change now pending in the  Congress.  Finally,  I will  discuss briefly
 some principles of premarket review which might  serve to clarify public
 policy questions for the regulation of chemicals.

      To further limit the scope of this paper and to keep the focus within
 an area for which I feel comfortable, I intend to deal only with the
 regulation of those chemicals which  fall under the heading of pesticides,
drugs,  food additives,  cosmetics, air and water pollutants,  and the
broad categorization of environmental pollutants which fall through the
cracks  of existing regulatory programs.
                                  36

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          EXISTING PREMARKET REVIEW MECHANISMS
                             Pesticides
      Along with drugs, the regulatory mechanism in existance for
pesticides contains the most severe requirement for premarket scrutiny
by a regulatory agency of all the toxic substances regulated by the
Federal Government.  As I am sure most everyone in this room is
aware,  the Environmental Protection Agency must grant registration
to each new chemical to be used as a pesticide before  it can enter the
channels of commerce.  In order to grant registration,  EPA must be
satisfied that unreasonable burdens to man or the environment will be
avoided through the intended use or misuse of the prospective pesticide.
As the burden of making this determination falls on the manufacturer,
the data in support of the registration must be  furnished by the
manufacture r.
                Drugs, Except Antibiotics and Insulin
      A similar premarket review requirement exists for drugs.  Under
the Federal Food, Drug and Cosmetic Act, each manufacturer of a new
drug must submit a "new drug application" which must be approved by
the Food and Drug Administration before the drug can be marketed.
Again, the manufacturer is responsible for furnishing the data necessary
to make the determination that no undue adverse effects are associated
with the drug.
               Food Additives, Antibiotics and Insulin
      Food additives, antibiotics, and insulin are all treated in much the
same manner under the Federal Food,  Drug and Cosmetic Act.

      With respect to antibiotics  and insulin,  when a specific use is
approved by FDA, a monograph is issued.  Subsequent manufacturers
of the specific antibiotic or insulin for the specific uses intended need
not obtain further FDA approval prior to marketing.

      Food additives are treated  in much the  same way.   Once a petition
for approval  of a food additive has been approved by FDA, subsequent

                                 37

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 manufacturers of the same food additive for the same purpose need not
 get individual clearance from FDA for marketing.  If he determines in
 his own mind that he is marketing the same  food additive for the same
 food he is free to do so.

       The primary distinction with this type of early warning system as
 opposed to that in effect for drugs and pesticides is that the manufacturer
 need only satisfy himself that he is in compliance with either a monograph
 or an approved petition rather than convincing either FDA or EPA of its
 compliance.  Obviously, the burden of proving safety or a lack thereof
 falls on different shoulders in each case.
                              Cosmetics
       There is no premarket review of the ingredients of cosmetics
 other than coloring.

       With respect to cosmetics, FDA can only take action when it
 proves a hazard exists from an ingredient of a cosmetic.  Again, the
 burden is on the Food and Drug Administration to prove the hazard
 rather than the manufacturer proving the lack of hazard.  And in most
 cases this information will only become available after the cosmetic is
 on the market.
                      Air and Water Pollutants
      Air and water pollutants present a special case as regulatory
mechanism is directed not at product composition, but rather towards
protection of specific environmental mediums through the application of
municipal and industrial effluent and emission control.

      Importantly, neither the Clean Air Act nor the Federal Water
Pollution Control Act contains a mechanism for the  premarket or pre-
manufacture review of environmental health and safety data for chemical
substances.
                                  38

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       Environmental Contamination From Consumer Products
      The most important class of environmental contaminants which is
 as yet unregulated are those constituents of consumer products which
 have slipped through the cracks of existing regulation for environmental
 effect.   These are materials which are not pesticides, drugs, food
 additives, or cosmetics.   Rather,  we are talking about phosphates in
 detergents, heavy metals and other constituents of consumer products
 like paint and drain cleaner for example,  PCB's, packaging, and a
 wealth of other potential hazards.  Included are all the consumer
 products which either escape sewage treatment or proper solid waste
 disposal or are more efficiently controlled by regulating the product
 rather than its disposal.  For example,  rather than remove the phos-
 phates from sewage effluent in the  Great Lakes, it may be far more
 prudent to control phosphates in detergents at the production level.

      It is these types of hazards that the  proposed "Toxic Substances
 Control Act" now pending in Congress is designed to control.
               LEGISLATION PENDING IN CONGRESS
      Limiting the definition of an "early-warning system" as I did
somewhat arbitrarily in the first part of this paper,  the amount of
proposed legislation to be examined is considerably  lessened.  Of
course,  any mechanism that assures that  scientists  and regulatory
agencies obtain good scientific information at as early a time as  pos-
sible will help to prevent problems before they become manifest. Ob-
viously,  a great deal of legislation is  pending to provide that assurance.
However, with respect to altering the system of regulation prior to
marketing,  there are two significant gaps  that remain.  The first is the
environmental effects  of consumer products mentioned previously.  The
second is the premarket review of safety data on cosmetics.
                             Cosmetics
      Cosmetics obviously do not present the same type of hazard as a
chemical with broad distribution or more intimate contact with biologi-
cal systems.  Neither are we talking about chemicals which would
greatly disrupt our economic system if premarket review of some kind
                                 39

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 were afforded.  As cosmetics have been known to present at least
 potential health risks, mercury in face creams,  for example,  some
 type of premarket review of safety data would seem justified.

       Several bills have been introduced in the Congress  which would
 provide for such premarket review.

       In the Senate, a primary proponent,  I am happy to say, has been
 Senator Magnuson along with Senator Eagleton.   Senator Magnuson's
 bill would require that each manufacturer  of a cosmetic now get the
 approval of the Food and Drug Administration before marketing.  The
 bill also contains a means of obtaining safety data on existing cosmetics.
 Senator Eagleton1 s bill  is similar as is legislation introduced in the
 House of Representatives by Congressman Paul Rogers.  It is probably
 safe to say that the Congress will not act soon on any of these
 proposals. ^2'  To my knowledge, the relevant committees in either the
 House or the Senate have not yet held hearings on the legislation.   Given
 this,  it appears unlikely that early action will occur.
                     Toxic Substances Control Act
       The Senate version of the  Toxic Substances Control Act, introduced
 early last year by Senators Hart,  Magnuson and Tunney could be de-
 scribed as a fourth generation descendant of the original Administration
 proposal. That the bill has been around this long is ample testimony
 to the complexity of the issues involved and to the controversies sur-
 rounding it.

       The pre-market review procedure contained in the Senate-passed
 Toxic Substances Control Act differs substantially from the laws regu-
 lating pesticides, drugs, food additives, and cosmetics.  The primary
 reason for the unique  procedure is the tremendous number of new
 chemicals which are developed and which could conceivably be regulated
 by the Toxic Substances Control Act. The coverage is necessarily
 broad in order to insure that new chemicals found in consumer products
 and new uses of existing chemicals found in consumer products will be
 encompassed by the umbrella of regulation. Although it is difficult to
 predict the exact number of chemicals so encompassed,  a report pre-
 pared by the Council on Environmental Quality estimates that several
 hundred per year  would fall into this category. '  '  The Committee on
 Commerce thought it extremely important to streamline as much as
 possible the premarket review mechanism in order not  only to avoid
administrative burden, but even more importantly,  to lessen the burden

                                  40

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of delay on the chemical industry that would exist if a standard pre-
market clearance procedure remained.

      The House version,  on the other hand,  does not contain the noti-
fication provision.  Under that bill, EPA would only get notice of those
chemicals for which a prior determination of "substantial danger" has
been made.

      The mechanism chosen requires each manufacturer of a new
chemical substance to give notice to the  EPA 90 days in advance of the
commercial production of any new chemical  or new uses  of existing
chemicals.  For those chemicals which EPA has predetermined to be
of questionable safety, test data would have to  be submitted along with
the  notification.   During the premarket review period,  EPA would have
the  authority to impose restrictions on the use or distribution of the
substance or could extend the  90 day premarket screening period for
an additional 90 days.  The legislation is drafted in a manner which
gives EPA broad authority to so limit the use or distribution of a chem-
ical during this period.

      The primary difference  between the premarket screening mech-
anism envisioned by the Senate bill and existing premarket clearance
procedures is that EPA must take affirmative  action during the pre-
market screening period to stop a chemical's production.  Under the
pesticide and drug laws, EPA must take affirmative action to let a
chemical on the market.  The Senate language is designed to lessen the
substantial fears of the chemical industry over EPA lethargy in granting
approval.  At the same time,  given the broad  discretionary authority
that EPA would possess during the premarket  screening period, there
is ample authority to prevent  unreasonable risks before the production,
distribution and use  of the chemical is irrevocable.
       PRINCIPLES OF PUBLIC POLICY WITH RESPECT TO
                    EARLY-WARNING SYSTEMS
      On the basis of some familiarity with at least one of the proposed
early-warning systems for the control of toxic substances, let me
propose some principles that might be useful in developing public policy
on early-warning systems.  Obviously it is difficult to formulate spe-
cific principles from the track record of the Congress as Congress has
not been entirely consistent,  legislating thoroughly in some areas  and
leaving others virtually untouched.  But at the  risk of stating the obvious,
let me mention briefly two principles which stand out in my mind.

                                   41

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       First,  the extent to which premarket review is given and the
 structure of that review must hinge on the likelihood of finding unbear-
 able threats and an assessment of the magnitude of those threats.   This
 must be balanced against the effect of delays on the affected industry.
 In other words, the extent to which inconveniences and delay are
 placed must depend on how frequently intolerable risks will be found
 and what the  magnitude of those risks will be.  In the case of chemicals
 which have the specific purpose of altering biological systems, like
 pesticides and drugs,  the answer, at least to me, is very obvious.
 These chemicals should not be disbursed to man or entered into the
 environment  until we are reasonably sure of the threat and have made
 a judgment that the threat is tolerable.

       On the  other hand, when we are looking for environmental threats
 from perhaps a few out of several hundred chemicals with little chance
 for a direct adverse effect on human health, we can stand to be less
 rigorous in our premarket review.  As I perceive it,  that is the prin-
 ciple which has been applied to the premarket screening provisions of
 the Senate-passed version of the Toxic Substances Control Act.

       The second broad principle  one could delineate is that the greater
 the latitude given an agency prior to market, the greater the assurance
 must be that indeed that discretion is executed  properly.  The means to
 provide that assurance are  usually found in the extent to which scien-
 tific  and technical information is released by the regulatory agency and
 the extent to which judicial  review of agency decisions is provided.
 Both of these issues are very difficult to resolve as several valid  com-
 peting considerations are often at work.

       With respect to releasing information,  obviously much of what is
 received by the regulator has competitive value.  Data with respect to
 intended uses,  chemical formulas, and industrial processes  are highly
 valuable pieces of information and usually are protected from release.
 On the other hand, in the hands of impartial scientists, toxicological
 data,  physical and chemical specifications,  and other data can be
 scrutinized and input sent back to  the regulators. On the other hand,
 government agencies are seldom anxious for this type of input.  The
 principle used in formulating the Toxic Substances Control Act in the
 Senate has been to release as much  of these  data as can be released
 without causing significant competitive injury.  This could allow the
 release of certain toxicological and  other data for review by the
 scientific community.  In the case of a chemical which is patented,
and the owner is protected,  a great  deal of information would be
released.  If it  is not,  however, and release of this information would
                                  42

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 significantly hurt him competitively, the manufacturers data would be
 withheld.

      The question of the extent to which the courts may review
 administrative decisions is a question of enormous significance.  His-
 torically, under the Administrative Procedure Act, administrative
 decisions may only be overturned if the court finds that the decision
 was reached arbitrarily or capriciously or is not supported by substan-
 tial evidence.  While these terms have been defined by the courts in a
 number of ways, the prevailing principal is that it is extremely hard
 to overturn agency decisions in court on the merits of the case.  Rather,
 most appeals of administrative decisions center around whether the
 procedural requirements of the decision-making process were violated.
 Rarely are  the merits examined in any great depth.

      I find this disheartening perhaps  owing to my lack of legal training.
 Certainly, proper procedures must be  followed, but I would think it
 entirely healthy for the administrative  process if the courts were allowed
 to examine  the merits of the Administrative decisions in greater detail.
 History remembers Christopher Columbus as  the man who landed in
 San Salvadore in the Bahamas, not as the man who took several wrong
 turns in getting there.

      Certainly in matters of technical judgment, the expertise of the
 administering agency should not be taken lightly.  Nor should the lack
 of technical expertise on the part of judges. In cases where technical
 matters  can be understood, however, and the judge satisfies himself
 they can be understood,  it does seem entirely fitting that greater lati-
 tude should be given to the courts to decide cases on the merits.

      As a footnote to this discussion,  I should point out that there has
 been little movement toward this end in the Congress.  In fact, far
 greater progress has taken place  at the State level where a number of
 States have given the courts near-blanket authority to review adminis-
trative decisions on environmental matters.

      Should the principle be developed on a broader scale, the quality
of the administrative decision making should be vastly improved.
                                  43

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                          REFERENCES
(1)  U. S. Congress, Senate, Environment Subcommittee, Committee"
    on Commerce,  Toxic Substances Control Act of 1973; Hearings,
    93rd Congress,  1st Session,  on S. 426 and Amendments 1, 8,  and
    9, Government Printing Office, Washington,  D. C.  (1973).

(2)  Library of Congress, Congressional Research Service,  Major
    Legislation of the 93rd Congress (November, 1973).
                                 44

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            AN INCIDENT OF INDUSTRIALLY RELATED
                 TOXIC PERIPHERAL NEUROPATHY

                       Bobby F. Craft, Ph.D.
              Deputy Associate Director for Programs,
                        Cincinnati Operations
         National Institute for Occupational Safety and Health
                             ABSTRACT
      Results of an ongoing investigation of an outbreak of toxic
peripheral neuropathy among workmen employed in a fabrics coating
plant indicate that of 128 individuals given complete neurological
examinations,  53 have been diagnosed as having a definite polyneurop-
athy.  Although the etiological agent(s) has not yet been conclusively
determined,  an organic solvent(s) used in the printing; operations is
highly suspect as a possible cause  of the problem.  This case will  be
used as an example to point out the inadequacies in available toxi-
cological information and to emphasize the need for systems of early
warning.
                          INTRODUCTION
      I will describe a recent outbreak of toxic peripheral neuropathy
among employees in a fabrics coating plant as an example to point
out the inadequacies of presently available toxicological information
and to emphasize the need for a comprehensive early warning system
capable of identifying, in advance,  the potential for this type of
problem.
                           CASE REPORT
      In-mid-August 1973, the Ohio Department of Public Health was
apprised by the Neurosurgery Service of the Ohio State University
Hospital of a case of peripheral neuropathy suspected to be of toxic
                                 45

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 origin.  The patient, a 43 year old male employee of a plant producing
 vinyl-coated wall coverings,  complained of having been weak since
 May.  Medical examination revealed that the onset of the disorder
 had been quite insidious.  The initial signs  included a  gradual develop-
 ment of tiredness or weakness of muscles,  extending over a period
 of months.  Sensory findings became evident as intermittent pares-
 thesias in the hands and feet  as if the fingers were asleep.  Some
 aching sensations in the arms and legs were also present.  Although
 there  was unexplained weight loss, it is of interest that there were
 no  symptoms of gasterointestinal disturbances, cutaneous lesions,
 loss of hair, autonomic symptoms or disturbance of vision.  Electro-
 myography confirmed the diagnosis of a relatively acute peripheral
 neuropathy.

       The patient also revealed that five or six other employees in
 his department of the plant (the print department) had  similar
 symptoms.

      An investigation was immediately initiated by officials of the
 Division of Occupational Health, Ohio Department of Public Health.
 Their evaluation confirmed that,  indeed, there were six other em-
 ployees in the print department of the plant who were diagnosed
 with peripheral neuropathy and that the problem perhaps  involved
 many  other employees  in several associated departments in the plant.
 The investigation further revealed that chemicals such as hexane,
 acrylamide, tri-o-cresyl-phosphate,  or thallium, commonly known
 to produce a toxic neuropathy, had not been in  use in the  plant for
 more than 10 years. The only significant change in operation or
 process was a substitution of normal methylbutyl ketone (MBK) for
 methyl-isobutyl ketone (MIBK).  The ventilation system,  particularly
 in the  print shop areas of the plant, was  noted  to be grossly inadequate,
 principally  due to poor design and maintenance.  Poor work practices
 were a significant contribution to exposure  — including eating at the
 work site and using solvents  as a skin cleaner. Because of the seri-
 ous nature of the problem, the uncertainty of the cause, and the
potential nationwide implications,  one of the most intensive and con-
 certed occupational health investigations in this decade was initiated
 involving several state,  federal and private organizations.
                                                 *
      Medical examinations including electromyograms (EMG) were
performed on 1, 156 employees  - practically the entire workforce  of
the plant.  Those with abnormal EMG findings  were given a thorough
neurological evaluation.  In order to better characterize  the disease
                                 46

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and to quantify the degree of involvement, Dr. Norman Allen, Ohio
State University, and his colleagues developed a rating scale in which
numerical values were assigned to:

      a.  Symptoms illicited from medical history

      b.  Neurological examination findings

      c.  Electrode diagnostic studies.
Any total score of 9 or above was classified as a definite polyneurop-
athy.  Of the 128 individuals rated under this scheme,  approximately
50 were found to have symptoms,  signs  and EMG's consistent with
a definite,  acute, peripheral neuropathy not attributable to other
known causes.

      Epidemiologic investigations revealed that the majority of
affected employees worked in the print department where a mixture
of MEK and MBK was used in large quantities as a solvent.  It was
shown that,  with one or two exceptions,  alljiefinite cases of neurop-
athy had exposure to essentially the same chemical substances as
did those working in the  printing areas.   Printing machine operators,
who had the highest attack rate as a group, were exposed to the highest
concentrations of solvent vapors.  In addition, they had significant
exposure through other routes.  Work practices  and a  lack of protec-
tive clothing offered potentially excessive skin exposure.  Employees
eating on the job demonstrated a greater risk of acquiring the disease
than those who did not.   Finally, the affected employees worked
significantly more overtime than non-affected employees.  Neither
MBK nor any of the other agents used in the plant have previously
been associated,  as far as we know,  with this particular type of illness,

      The facts or circumstances which implicate MBK as the  possible
etiological agent are as follows:

      1.   MBK was first used in the plant in August,  1972,  and
          was put into full use by December, 1973.  The first
          symptoms of the disease appeared in December,  1973.

      2.   No ocher changes in the materials  or processes were
          identified.

      3.   Workers in an almost identical coated fabrics opera-
          tion on the west coast had  similar  exposures except
          that MBK had never been used in that plant.  Al-
          though they were examined in a similar manner,  none
          of these workers were found to have any evidence of
          peripheral neuropathy.

                                 47

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      4.  Two isolated cases of peripheral neuropathy in
          Connecticut and Iowa with signs and symptoms very
          similar to that described here also were occupa-
          tionally exposed to MBK.

      5.  Chemicals  commonly known to cause peripheral
          nerve damage have essentially been ruled out on
          the basis that they have not been used and no evidence
          of their presence has been detected by laboratory ana-
          lytical evaluation of materials used and biological
          samples obtained from affected workers.

      I am sure that  there are many isolated cases of peripheral neuro-
pathy for which  no cause is ever discovered, even after extensive in-
vestigation.  When this happens,  any chemical in the patient's environ-
ment can be a scapegoat.  Some of the reports of alleged chemical
neuropathy are not very convincing and once a  substance has been
blamed for a particular toxic effect, the case against it  may be self-
perpetuating.   I fear that this kind of situation  may hold here and in
spite of the fact that  we have stated that a causative has  not yet been
conclusively established in this case, I note from articles in the press
and based on some industries withdrawing it from use in their plants
that MBK has been tagged as a peripheral neurotoxin.

      The results of  animal studies presently underway  will be critical
in determining the actual cause of the problem.

      The use of a large number of chemical compounds in this plant,
many for which there is little or no toxicological information available,
has markedly complicated the assessment of the problem.  In our in-
vestigation, one  of the first steps was  to obtain a comprehensive list
of all chemical raw materials used in each area of the plant.   You
might be  surprised at what a difficult task this is for some companies.
In this case, for some of the compounds,  the company was able to pro-
vide only the supplier's tradenames.  For some, the company had no
idea what actual  chemicals by scientific name they were using — much
less, information about the toxicity.  This points out the need for some
uniform system whereby the purchaser of a chemical substance is able
to identify the compound that he is using and to have information on its
toxic effects,  special precautions,  symptoms of exposure, etc.  Section
20(a)(6) of the Occupational Safety and  Health Act of 1970(') requires
the Secretary of the Department of Health, Education, and Welfare
to publish, on an annual basis, a  list of all known toxic substances and
the concentration at which such toxicity is known to occur. The  1973
list(2) co'ntains over  12, 000 compounds for which published toxicity
information is available.  The Occupational Safety and Health

                                 48

-------
Administration (OSHA) has promulgated safe exposure standards for
only 450 chemical substances. (3)

      That gives you an idea of where we are in terms of just basic
toxicological information.  The  research required to develop suffi-
cient data to establish safe industrial exposure standards for all the
potentially toxic chemical compounds in use is  astronomical. Addi-
tionally, while gross manifestations  like coma  or convulsions are
readily recorded and attributed  to actions of a poison on the  central
nervous system,  effects on the peripheral nervous system may escape
notice.   Detailed studies of functional and structural changes in the
central and peripheral nervous systems do not  often get carried out in
conventional toxicity tests. &)

      These kinds of studies address a single agent concept while it is
a rare situation indeed when a workman in an industrial situation is
exposed to only one toxic chemical compound.  More typically,  work-
men are subjected to a variety of chemical agents as well as to noise,
heat, radiations, and vibrations — all superimposed on the additional
stresses resulting from various psychological or motivational factors
associated with the workplace.

      Although the synergistic,  additive, potentiation and antagonistic
actions of some combinations of environmental contaminants have been
documented, there has been relatively little work done in this very
important area.  When one thinks of  all the possible combinations
and permutations of the thousands of chemical and other stresses that
would require study, it is practically impossible to know where to
begin.  Recognizing that present collective resources  available to
attack this type of problem can only scratch the surface of the issue,
it is imperative that an effective and responsive system be developed
whereby research priorities can be established that are appropriate
to the needs of a variety of organizations and agencies concerned with
toxic substances.

      In closing,  I would like to add  a word of  caution in the context
of the theme of this seminar. A system of early warning for toxic
substances certainly depends on the availability of appropriate toxico-
logical information - but that in itself is not enough.  Some mechanism
is required whereby the potential for exposure  can be  identified and a
means of assuring that exposures are effectively controlled  so that an
incident like I have just described is prevented.  The  "system" might
well tell us that compound A in combination with compound B at x con-
centration for y days will cause peripheral neuropathy and even that
these types of exposures are likely to occur in a particular type of

                                 49

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industry,  but if we do not have a mechanism to impart that information
to the appropriate people who must take.action to see that it does not
occur, then we will continue to see these types of episodes.
                          REFERENCES
(1)  Public Law 91-596,  91st Congress, S.2193 (December 29, 1970).

(2)  The Toxic Substances List,  1973 Edition, NIOSH, DHEW
    (June, 1973).

(3)  Subpart 6,  Occupational Health and Environmental Control - 1910,
    93 Air Contaminants, Federal Register, 3J7, (202) (October 18,
    1972).

(4)  Barnes,  J. M., "Toxic Chemicals and Peripheral Neuropathy:
    Experimental Studies", Proc. Roy. Soc.  Med., 62 (February
    1969).
                                 50

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          ESTABLISHING ENVIRONMENTAL PRIORITIES
      FOR SYNTHETIC ORGANIC CHEMICALS: FOCUSING ON
                        THE NEXT PCBIS

                         Philip H. Howard
             Syracuse University Research Corporation
                            ABSTRACT
      Well over 9000 synthetic organic chemicals are produced in com-
mercial quantities and annually total approximately 140 billion pounds
in the United States.  Many of these chemicals,  such as pesticides,
detergents, PCB's and phthalic acid esters, have become well recog-
nized environmental contaminants.  Because of the large number and
quantity of organic chemicals being produced, a procedure to set
priorities for environmental  research, monitoring, protocol testing
(e.g., persistence and toxicity),  and regulatory action is necessary.

      This paper discusses (1) the parameters which are important to
establishing such a procedure, (2),the quantity and quality of the
information presently available as well as potentially available after
the passage of the Toxic Substances  Control Act, and (3) the difficulties
of integrating the parameters to provide  an overall ranking of the chem-
ical's environmental hazard potential.  Special emphasis is placed on
the unique considerations necessary with synthetic organic chemicals
in contrast to inorganic chemicals.
                          INTRODUCTION
      Well over 9, 000 synthetic organic chemicals are produced in
commercial quantities and annually total approximately 140 billion
pounds in the United States. '*'  Many of these chemicals,  such as pes-
ticides, detergents, PCB's and phthalic acid esters, have become well-
recognized environmental contaminants.  Some of these chemicals are
intentionally released into the environment for economic purposes (e.g.,
pesticides) and others are inadvertently and accidentally released
during manufacture, transport, use,  and/or disposal.   The large number
and quantity of organic chemicals being manufactured provides
numerous candidates for such releases to the environment.  Therefore,

                                  51

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 a procedure to anticipate future environmental contaminants and to set
 priorities for environmental research, monitoring and regulatory
 action is necessary.

      Anticipatory action for environmental contaminants is extremely
 important because of the lag period between the reduction of the release
 of contaminants to the  environment and the reduction of concentrations
 in the environment.  This is especially true of the many lipid soluble
 organic chemicals which, when incorporated into  the food chain, can
 biomagnify.  As an example, one projection indicates that if the use
 of DDT were decreased to zero by the year 2000,  concentrations in
 the higher levels of the food chain would continue  to rise for another
 decade. I2' Even with a total elimination of DDT use,  the concentration
 in fish would rise slowly for a  few  years.  Thus,  by the time a delete-
 rious biological effect  caused by a  contaminant is noted,  years may
 elapse  before corrective action will result in environmental quality
 improvement.  One can envision an environmental thalidomide which
 might have exceeded the threshold  concentration before the effect was
 realized, and which might take years before remedial action could be
 effective.                          *~

        This type of contamination may already be entering the environ-
 ment.  In a review of the water quality information up to  1970,  Davis
 et al. (3)  stated that only 66  compounds were identified of the 496 organic
 chemicals reported to  be or suspected to be in fresh water. An EPA
 laboratory has isolated 34 different non-pesticide synthetic organic
 chemicals in water  at the lower end of the Mississippi River'4), which
 happens to be a source of drinking water for half the people in the State
 of Louisiana.

        Which of these  chemicals or new chemicals coming on the mar-
 ket should be tested first?   Which last? Which should be monitored
 for in the environment?  Which should be regulated or banned from the
 market?  A meaningful set of priorities are obviously necessary.
           ESTABLISHING PRIORITIES FOR SYNTHETIC
                       ORGANIC CHEMICALS
       Assessment of any potential contaminant, whether it is from
occupational exposure or environmental sources,  requires the consid-
eration of two primary questions (1) at what concentrations does the
compound cause any deleterious effects (toxicity) and (2)  does the

                                  52

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compound reach a biological species in high enough concentration to
cause the effect?  With environmental contaminants,  often the source
is quite distant from the biological species being affected which makes
the job of assessment much more difficult.  However, by reviewing
available information on toxicity,  production, transport, uses, envi-
ronmental stability, and the  chemistry of the many potentially danger--
ous compounds, priorities can be set in such a way as to markedly
increase the change of identifying environmental hazards.
                  ENVIRONMENTAL TOXICOLOGY
       Perhaps no compounds known can be described as toxic or non-
toxic apart from the conditions in which it reacts. Sodium chloride and
carbon dioxide, for instance, can be either beneficial or lethal to human
life depending on their concentration.  Consequently,  in defining the
toxicity of a  given substance, a number of parameters -  e.g.,  concen-
tration, duration and route of exposure, temperature, species,  stage
of life cycle, etc. — must be defined or at least implied.  For most
commercial  organic chemicals, the toxicity is most often described
in terms of acute exposures to man or related mammals, prompted by
a concern  for industrial safety.  For compounds  such as pesticides
whose use may indicate more direct exposure to man or commercially
important  animals, chronic toxicity data may also be available.  How-
ever,  more definitive toxicologic information — including studies of
carcinogenicity,  teratogenicity, and mutagenicity — are  often available
only for those compounds designed for direct human consumption:
drugs, food additives, cosmetics, etc.  For example, of the 496 organic
chemicals reviewed by Davis et al. '•*) only 120 compounds (24%)
had been tested for carcinogenicity and only 32 compounds (6%)
for teratogenicity. For environmental contaminants, information on
chronic and more definitive toxicity is most desirable.

       Such  detailed toxicity studies are, of course,  expensive.  A
reliable evaluation of chronic toxicity alone has been estimated to cost
between $100, 000 to  $200, 000 per chemical. (5) Such costs may often
be prohibitive in the  development of new and possibly useful chemicals
with only marginal or questionable commercial value.  Even with the
passage of the Toxic Substances Control Act, it is unlikely and may
be unreasonable  to expect that all of the 300 to 500 new chemicals
                                       /M
annually introduced for commercial usev°' will receive anything ap-
proaching a  complete evaluation of toxicity.  However, it is obvious
from past experience, that certain chemicals should receive extensive
testing regardless of cost.  Which compounds will receive  such

                                  53

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extensive testing should then be dependent on not only the available
toxicity data but also a number of more readily described or projected
parameters that might be considered under the headings of environmen-
tal contamination potential, environmental stability,  and probable
environmental distribution.
                  ESTIMATING ENVIRONMENTAL
                  "CONTAMINATION POTENTIAL
        The potential for accumulation of a chemical in the environment
 is dependent upon whether it is released to and persists in the environ-
 ment.  Rarely is this information available in quantitative form.  Data
 indicative of release to the environment, such as quantity produced
 (magnitude of the potential contamination), sites of production, syn-
 thesis methods, waste treatment, product uses, are presently available
 for only a few organic compounds. The U.  S. Tariff Commission,
 which compiles the most comprehensive listing of synthetic organic
 chemicals**',  only publishes production and  sales figures for approxi-
 mately 10% of the compounds.  Other general sources of information
 include the Chemical Economics  HandbookC?) and the Encyclopedia of
 Chemical Technology(8).These  references  will provide marketing
 information on production and use for many but not all of the organic
 chemicals.  When the Toxic Substance Control Act is passed,  this type
 of information will be routinely submitted to EPA.

        Correlation of this marketing information into even qualitative
 estimates of release is one of the least understood and one of the  most
 important factors in determining environmental hazard.  Physical prop-
 erties may provide some insight.  Gases and volatile liquids are often
 released to the environment.  Past experience with other known envi-
 ronmental contaminants may also provide some assistance.  Nisbet
 and Sarofim'" in a study of PCB's routes into the environment con-
 cluded that PCB's used as hydraulic fluids, lubricants and heat exchangers
 provided the major source of water contamination, whereas PCB's used
 in transformers and capacitors were mainly deposited and mostly retained
 in land fills (see Table I).  Compounds used  as detergents or water
 emulsifiers are known to get out into streams and rivers. As more
 contaminants are recognized and their sources located,  the correlation
between marketing data and release to the environment will become
more exact.
                                  54

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(Jl
01
                                                                  TABLE I


                                                QUANTITATIVE ESTIMATES OF RATES OF LOSS


                                                OF PCBs INTO THE ENVIRONMENT IN 1970 (9)

Transformer

Capacitors

Miscellaneous

Plasdcizer '

Hydraulic Fluid
»nd Lubricant
Heat Exchangers

Total
Quantity Sold
for Use (Ibs. )
13.9 x 106

26. 7 x 10*

1. 6 x 10e

19. 5 x 10*


7.4 x Id"
4. 0 x 106

73.1 x 10"
%of
Total
Sold
19

37

2

27


10
5

100
% of Sales
Total that was
to Replace
Discarded PCBs
10

50

~100

{~80-90
~10-20


~100
50


Quantity
Discharged
into the
Environment (Ibs)
1.39 x 10s

13.35 x l(f

1.60x 10*

16. 60x 10"
2.92x 106]


***
42. 8 x 10* (
(incineration.
open dump or
landfill)
2-4x10*


8-10 x 10"

45.25 x 10"


36. 0 x 10* \
/

Y*. 0 x 109 1

0. 8 x 10* (
vaporization of
remained in
the dump or
landfill
destroyed by
incineration
or open burning
vaporisation
from open-burn
plasttcizer
•
leaks and disposal of industrial
fluids (mostly into fresh and
coastal waters)

                ***This figure is somewhat higher than the sum of the quantity discharged due to replacement.

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      ENVIRONMENTAL STABILITY OF ORGANIC CHEMICALS
        The importance of environmental stability to setting priorities
 for potential environmental contaminants is often underestimated.  If
 a compound degrades into innoxious material before it reaches a
 biological site, its hazard is relatively low.  This potential degradation
 mechanism is especially important with organic chemicals.  In con-
 trast,  environmental contaminants such as heavy metals may change
 chemical form (e.g., methylation) or valence state but can not be
 degraded into innoxious  substances such as carbon dioxide and water
 as can organic chemicals.

        Organic chemicals in the environment can be both chemically
 or biologically altered.  However, the most important process contrib-
 uting to the elimination of organic chemicals from the  environment is
 biodegradation.  The action of microbial enzym.es generally results in
 end-products that are entirely inorganic. '^'  In contrast,  photochem-
 ical or other chemical processes in nature usually result in relatively
 minor  alterations of the parent compotind,  but may provide the slight
 alteration needed to change a persistent compound to a biodegradable
 one.

        For many years it was  felt that the  microbial communities of
 soil and water  could destroy any organic compounds which were placed
 in the environment.'   '  Recently, however,  it has become evident that
 microorganisms  are not infallible and that  some molecules are inher-
 ently recalcitrant to microbial degradation. ^"» ^ '   Practical experi-
 ence with chlorinated pesticides and highly substituted detergents has
 been especially enlightening.   This resistance to biode gradation is
 dependent not only on chemical structure of the contaminant [ "molec-
 ular recalcitrance" (12)j DUt also on the environment (soil, freshwater,
 marine water,  atmosphere, etc. ) in which the contaminant comes in
 contact.

        The relationship of chemical structure to biodegradability has
 been comprehensively reviewed'     ' and is briefly summarized in
 Table II.  Chemical'   ^ and photochemical^"""*") reactions in the envi-
 ronment have also been reviewed.

        The information available on environmental  stability of organic
 chemicals,  which might be used for setting priorities, is rarely  very
 detailed,  except when compounds of similar generic structure have
been noted as environmental contaminants.   Usually a biode gradability
test has been run, especially for compounds that might have to pass

                                   56

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                               TABLE II
                         Relationship Between
                 Chemical Structure and  Biodegradation
Less Persistent
                                 More Persistent
 Water soluble
                                Water-insoluble
      H
      I
  c - c - c -
      I
      H
     - C - C -  C -
     - C - C - C
           I
           C
       R - CH2OH
       R - CHO
       R - C02H
Br, C1-CH2(CH2) c02H
       R-C02R
           Cl,  Br
CH3-(CH2)x-CH-(CH2)XC02H
      R - 0 - R
CH3(CH2) CHC02H
        A
                                                                  Cl
          C02H
                                                                   S03H
                                    57

-------
through a sewage treatment plant.  But the difficult task of modelling
the laboratory environment to accurately reflect an ecosystem is only
too apparent when one compares the test results with the actual  envi-
ronmental behavior of the chemical.  However, by combining the avail-
able information with the projected chemical structure biodegradability,
it is possible to roughly estimate the environmental persistence.  Again,
with the passage of the Toxic Substances Control Act, information on
environmental stability of new compounds will be more  systematically
generated and hopefully more appropriate to the media to which  the
compound is released.
                  ENVIRONMENTAL DISTRIBUTION
        Once it is decided that a compound is released to and persists
 in the environment,  it is important, in terms of hazard assessment,
 to be able to estimate  where the chemical might concentrate to dangerous
 levels in the biological cycles of the environment.  Predicting environ-
 mental distribution of  a contaminant as a diagnostic tool for hazard
 assessment has some  possibilities.  However,  elemental mercury was
 considered to  be immobile in the environment for many years.   Further-
 more, Woodwell'1'' has suggested that one lesson to be learned from
 iodine 131 is that "even when the pathways are well understood, it is
 almost impossible to predict just where toxic substances released into
 the environment will reach dangerous levels".  Using physical  properties
 such as  lipid solubility, vapor pressure, and ambient state  (gas, liquid,
 solid) as indicators of bioaccumulation and mobility provides some
 predictive possibilities.  The use  of model ecosystems has become
 quite popular'   ', but,  for the most part, because of the cost involved,
 these have been reserved for study of already acknowledged environ-
 mental contaminants.  However,  projection of environmental distribu-
 tion based on available physical properties,  although quite an inexact
 parameter, can provide some inputs to hazard assessment.
    EXAMPLES OF ORGANIC CHEMICAL HAZARD ASSESSMENT
        Perhaps the most difficult task in setting priorities is ±o combine
the above parameters in some type of rational fashion.  One must first
come to the realization that a result based on parameters that are quite
inexact will obviously be qualitative,  not quantitative.

                                  58

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      The complexities involved are best explained by examining some
examples.   Table III summarizes a great deal of information that was
gathered on five general groups of chemicals^*)   All of the  chemicals
have been produced in sizeable commercial quantities for many years
but much of the information that is available is not radically different
from what would  be available for a new commercial chemical.

      Chlorinated naphthalenes provide a good example.  The similarity
between PCB's and chlorinated naphthalenes in terms of chemical and
physical properties and commercial uses is most striking.  Both chem-
icals have been shown to cause chloracne and liver damage in man and
many are relatively toxic at low levels.   The major differences between
the two are  the production levels and the uses.  In 1970 PCB's  were
produced in approximately 70 x 10" Ib a year, although the level has
decreased since then.   The market for chlorinated naphthalenes is
less than 5 x 10° Ib per year and appears to be decreasing.  A  major
use for both chemicals is as a capacitor impregnate  (PCB's — light
fixture capacitors,  chlorinated naphthalenes — automotive capacitors).
However, it is suspected that these capacitors end up in dumps or land
fills'"' and  since they are contained in a closed system their ability to
leach out is relatively low.  Formulations used as oil additives, hydrau-
lic fluids, and heat exchanges  (PCB's - 11.0 x  10^ Ib, chlorinated
naphthalenes	1.3 x 10  Ib) probably have the greatest potential for
release to the environment.  With chlorinated naphthalenes,  the formu-
lation  consists of mono- and dichloronaphthalenes which should be much
less environmentally persistent.  These projections  of environmental
persistence are based mostly on analogy with PCB's.  Only the mono-
chloronaphthalenes have been experimentally tested.

      The penta- and hexachloronaphthalene formulation is of some
concern.  They exhibit high mammalian toxicity,  probably are quite
persistent,  and are used in ways  (electroplating stop-off compounds
and carbon  electrode impregnates) which might lead to environment
release.  However,  they are produced in relatively small quantities
(0.4x 10" Ib). Thus, although there is some reason to be concerned
about chlorinated naphthalenes, they certainly seem to be much less
of a problem then were PCB's and can be fairly safely assigned a lower
priority than PCB's.  Some of the formulations can be assigned an
extremely low priority (e.g.,  the hepta- /octa chloronaphthalenes -
low production,  relatively low toxicity).

      But what about compounds,  such as silicones,  that have  consid-
erably different parameters than chlorinated naphthalenes?  The
silicone fluids are produced in large quantities (60 x 10" Ib) and are
probably released into the environment in significant amounts  from

                                  59

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                                      TABLE III
Pactora Efftctlnt the Dt-gne of Potential Environmental Hazard for Selected Compound* (21)
Compound
Chlorinated Naphthalenes
(Halovaxaa)
HOOO-/DI-
Trl-/t*lra-
Peot*-/H*xa-
•apta-XOcta-
flllcoM* (elloxmnee)
flulda
lilicoo* glycole
lubber* (alaatomere)
•aatsa
fluorocarbona
CCl,f
cafr2
CHClPj
C12C2F4
CWj
leilni * Elaetomare
(c.g- Teflon)
Produce loci
Recent Lite
Annual of
Production Growth
(10' Iba)
* 1.) Stabled!
12.7} Siovlr
rlalni
^•0.40 Dacllnlnf
0)
% 0.03 Meltnlni
(t)
60 Ualnt
IS Uatn»
16. * KUinf
U.I liiinc

»l
WO 6-K/yr.
80
17
It
[fiyalcal Proprrtl**
Phyaical Llpld
Fan Solubility
Liquid Bl(k
Solid High
Solid Hi|h
Solid Hl|h
Liquid tM-Hl|h
Liquid Mad-Blgh
Solid 	
(polymar)
Solid 	
(polyur)
Liquid HI|K
Caa Htd-Hl(h
Caa Kadiua
Caa HadluB
Liquid Hcdlua
Solid 	
(Polvo.-r)
Uaia
Oil and dy*
addltlva
LUCO capacitor
Utpr*t<«C*
Electroplating
carbon
•Itctrodaa
Uoknovn
ax*i, poliah,
oaawtlca,
•alilona.
ratban* foama
Jactrlcal
Inaulatlon.
lactrical
naulatlon,
ainta. and
oatlnta.
Uroiol
ropallanti
Icroiel
rop.ll. 4
•frl(«rant
toft Iterant
Unaol
ropcllant
olvrnti
naulatlon.
oat inn
Ifl»lron-
Mntal
Piralattnc*
Lov-«od.
Hod-High
High
High
High
\
High
m$>
High
taaldracc
tlawa
>• 10 yaara
30 yaara
High
High
Nigh
High
Tcoilelty
Llvar aacroaia and chloracot
Chloracna TLV ALD
Xigatlvi
~
Poaltlw
—
"*~
> •«/•*
9.5 •*/•
—
Chronic pathological
affacta
} g/kg faid/rat x
2 yaara - no affatc
•"•• 	 *~*
	
-
In auja, plaaia Vitamin A
reduced
(oral) Tvratoganlc,
•utagan. carcin.
affacta


100 •(/rat/dog
x 55 day*
116 at/kg P.M.
(abM»>
1000 a*/rat
LC>,
ducfci
'I/if
(ud x
t dara
—
	
*"—
LCld
daphnla
1-g/l
500-
1000
X>/1
	
""
—
-
—
—
Taracogantc,
•lutagan. , caraln.
affccta
	
— —
	
Smoth wall
tumor after
Implant
Bam cauaad hinan death froa cardiac arrhytlmlaa
(hlih doaaa)
TLV
9,600 «g/»>
4.950 aig/B1
111 • '
7,000 •(/•>
7,600 ml/ml
	
Oaath
Xagaclva
rat, 101
x 2 hr.
Xcgatlva
rat. 20X
x 2 hr.
lagatlv*
rat. 20X
x 2 hr.
Foil tin
Cuinaa piga
> 20X x 1
houra
roaltlva
rat, 10Z i
* houra
	
Cardiac aaoalt.
to aplnaphrina
roaltlva
1.211 x 5 B-U.
Poaltlv*
5.01 x S Bin.
Foaltiv*
5.0X x 5 aln.
Poiltlv*
5.01 x 5 Bin.


Taratogeaic,
•utagenlc ,
carciBogaatc
affacta
	
	
	


	
	

-------
TABLE III (continued)
Compoind
Benrenepolycarboxylates
Phthalie anhydride
and *cld
Xaophthallc meld
Terephthallc acid
(6 dimethyl «at«r)
Trimellltic acid
• anhydride
Pyromellltic acid
Cblorophenols
p-Chlorophanol
2 , 4-Dlchlorophenol
2,4,5-Trlchloro-
phenol
Fentachlorophenol
Production
Htcent Hate
Annual of
Production Growth
(106 Ibs)
794 Rising
95 Bialng
3.321
11
(esters)
> 2 Using
53 Declining
(aa 2.4-D)
14 Declining
(aa 2.4,5-T)
SI Rising
(4X/yr)
physical Properties
Physical Upid
Pen Solubility
Solid Medial
Solid KedluB
Solid Med-Bigh
Solid Ked-Low
Solid Med-Lov
Solid Medium
Solid Hed-Bigh
Solid Med-High
Solid High
Uses
Produce eaters
for plasti-
eizera.
Alkyd resins
Synthesis* of
hy-products,
Alkyd and
polyester resins
Polyethylene
terephthalate
for fiber « fllai
Produce esters
for plaatlclters
Polyamlde
polvners
Kav material
esp. for 2,4-D P
Raw material
for 2,4-D
Raw material
for 2,4,5-T
Wood
preservative
Environ-
mental
Persist-
ence
Low
Low
Low
Low(T)
Low(?)
Lov-Med.
Med.
'id-High
Ked-HIgh
Toxlclty
U>SO (oral)
Z.2 g/Ks
mice
	
S g/kg mica
1.25 - 2.5
g/kg mice
	
intraperit
1.67 g/Kg
•ice
4.2 g/kg
mice
3.7 g/kg
mice
	
—
Inbal.
30-90 g/1
mice & rats
	
	
	
	
Teratogenic. muta-
genlc, carcinogenic
effects
Negative -
(teratogenic)
	
1 ' '••
	
	
Higher chlorinated phenols can cause liver and
kidney damage
LDso (oral)
500 ag/Kg
rat
3600 mg/Kg
rat
2460 mg/Kg
rat
135-205
mg/Kg rat
Intraperi-
toneel
28/mg/kg
rat
430 mg/Kg
rat
355 mg/Kg
rat
56 mg/Kg .
rat
TL fish TLV Teratogenic,
Kutagenlc,
carcinogenic
effecta
14 mg/1 	 	
— 	 	
	 	 	
05-. 16 0.5 mg/mj 	
ppm

-------
 a variety of uses (e.g. , antiforming agents, waxes and polishes).  There
 is good experimental evidence that these compounds are extremely
 stable  in the environment.  However,  the mammal toxicity data would
 suggest that these compounds are perhaps one of the more innocuous
 chemicals ever produced.  Some of the fluids are even allowed as
 food additives.  In contrast,  one study with daphnia suggests an
     Q of 1 ppm.
       The silicons rubbers and resins appear to have a very low prior-
 ity because of their lack of mobility.  Their stability suggests that very
 little material is degraded into compounds that might accumulate in
 biological systems.  Local tissue response to  such silicone implants
 is of medical interest and the phenomena of solid-state carcinogenesis
 is receiving warranted investigation, but its relationship to environ-
 mental hazard is remote at best.

       Several questions arise from this comparison.  How much should
 one rely on available toxicological data?  How important are production
 levels?   In other words, how should one weigh each of the parameters
 that are relevant to hazard assessment?  The  answer is that at this
 time correlations can only be approximate.  However, because of the
 large numbers of chemicals to be assessed, these approximations will
 have to be made to allow some numerical assessment.  As more
 experience with both past and present environmental contaminants is
 gained,  these approximations will become more and more exact.

       None of the five chemical groups in Table III can be totally
 eliminated as an environmental hazard, but many formulations can be
 assigned low risk.  Within groups relative risk can more easily be
 assigned.

       The evaluation process  clearly provides  some research  and infor-
 mation needs. A crucial piece of data for chlorinated naphthalenes is
 whether the penta- and hexa chlorinated compounds are released to the
 environment from their use.   By examining the housekeeping practices
 of the electroplating industry  and the carbon electrode manufacturers
 and users, this question could be easily resolved.  Also, some selec-
 tive monitoring might be in order.

      With silicone s  high priority should be given to clarifying the
 effects of the compounds on lower organisms and  selectively monitoring
 some environmental  samples.  One projected use  of silicones is as an
antitranspirant for plants to reduce losses from the water table.  Before
this is allowed, a great deal more information on environmental persis-
tence, fate, and  effects is needed.

                                  62

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                            SUMMARY
      Assessment of environmental hazard from organic chemicals is
.possible by reviewing and integrating available information on chemistry,
 production and use, environmental stability, and toxicity.  It  is an in-
 exact process subject to error that works fairly well with chemically
 and commercially related compounds and somewhat less exact with
 other compounds.  However,  such reviews are extremely helpful in
 setting research and data gathering priorities and in identifying high
 risk hazards.  Such assessments  should be continuous in order to incor-
 porate new data as it becomes available.
                       ACKNOWLEDGMENTS
      The research was supported in part by a contract from the U. S.
 Environmental Protection Agency, EPA-68-01-2202.  The author wishes
 to thank P. R. Durkin, L. H. Naum, and J. Saxena for their valuable
 comments during the preparation of this manuscript.
                           REFERENCES
  1.   U. S. Tariff Commission, Synthetic Organic Chemicals;  U. S.
      Production and Sales,  1960-1970,  Government Printing Office,
      Washington,  D. C.

  2.   J. Randers and D.  C.  Meadows, "System Simulation to Test
      Environmental Policy:  A Sample Study of DDT Movement in the
      Environment", MIT, Cambridge,  Mass.

  3.   T. R.A. Davis, A.  W.  Burg, J. L. Neumeyer, K.  M. Butters,
      and B. D. Wadler,  "Water Quality Criteria Data Book. Vol. I;
      Organic Chemical Pollution of Freshwater", 18010DPV12/70,
      Government  Printing Office, Washington, D. C.

  4.   S. S. Miller, "Are You Drinking Biorefractories Too? " Environ.
      Sci.  & Technol., 7, 14 (1973).

  5.   Chem. & Engr.  News  (November  15, 1971), 26.

                                  63

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  6.   Council on Environmental Quality,  Toxic Substances, Government
      Printing Office, Washington, D.  C. (1971).

  7.   Stanford Research Institute,  Chemical Economics Handbook,
      Menlo Park, California.

  8.   Encyclopedia of Chemical Technology, John Wiley & Sons, New
      York.

  9.   I. C. T. Nisbet and A. F. Sarofim,  "Rates and Routes of Trans-
      port of PCB's in the Environment", Environ.  Health Perspec-
      tives,  Expr. Iss. No.  1, 21  (1972).

 10.   M.  Alexander, "Pollutants That Resist the Microbes",  New
      Scientist, £5, 439 (1967)..

 11.   This is referred to as the "Principle of Microbial Infallability",
      [(12),  p 37]; See also E. F.  Gale,  The Chemical Activities of
      Bacteria, Academic Press,  New York (1952,  p  5.

 12.   M.  Alexander, "Biodegradation:  Problems of Molecular
      Recalcitrance and Microbial Fallibility", Adv. Appl. Micro-
      biology,  7,  35 (1965).

 13.   M.  Alexander, "Nonbiodegradable and Other Recalcitrant
      Molecules", Biotechnol. Bioeng.,  1£, 611 (1973).

 14.   D.  G.  Crosby, "The Fate of Pesticides in the Environment",
      Ann. Rev. Plant Physiol., 24, 467 (1973).

 15.   D.  W.  Ryckman, A. V. S.  Prabhakara Rao, and  J. C. Buzzell,
      Jr., Behavior of Organic Chemicals in the Aquatic Environment;
      A Literature Critique, Manufacturing Chemists  Association,
      Washington, D.  C.  (1966).

 16.   D. G.  Crosby,  "Nonmetabolic Decomposition of Pesticides",
      Ann. N.  Y.  Acad. Sci.,  160, 82  (1969).

 17.   D. G.  Crosby and L.  Ming-Yu, "Herbicide Photodecomposition",
      in Degradation of Herbicides, P.  C. Kearney and  D. D. Kaufman
      (Eds.), Dekker, New York, p 321.

18.   J. R.  Plimmer, "Photochemistry of Halogenated Herbicides",
      Residue Reviews, 33, 47 (1970).
                                 64

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19.   G. M. Woodwell,  "Toxic Substances and Ecological Cycles",
      Scient. American, 216,  24 (1967).

20.   R. L. Metcalf,  G. K.  Gurcharan, and I. P. Kapoor,  "Model
      Ecosystem for the Evaluation of Pesticide Biodegradability and
      Ecological Magnification", Environ. Sci.  Technol., 5,  709 (1971).

21.   P. H. Howard and P. R. Durkin, "A Study of Benaenepoly-
      carboxylates, Chlorinated Naphthalenes, Chlorophenols, Si lie ones,
      and Fluorocarbons", Syracuse University Research Corporation,
      Prepared for the Office  of Toxic Substances, EPA, Contract
      68-01-2202.
                                 65

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       A LABORATORY MODEL ECOSYSTEM AS AN ELEMENT
      IN EARLY-WARNING SYSTEMS FOR TOXIC SUBSTANCES

                           Robert L. Metcalf
                  Institute for Environmental Studies
               University of Illinois, Urbana-Champaign
                           INTRODUCTION
      For the past seven years our laboratory has been studying the
 development and utilization of a laboratory model ecosystem for
 the evaluation of the micropollutant potentialities of a variety of
 synthetic organic compounds.  From this work we have evolved a
 relatively simple and reasonably reproducible terrestrial-aquatic
 system (Metcalf et al 1971, Metcalf 1972,  Metcalf 1974b), and have
 characterized the degradative fate of more than 70 compounds includ-
 ing organochlorine,  organophosphorus, and carbamate insecticides,
 insect growth regulators, herbicides, fungicides, toxic impurities
 and degradation products such as DDE, photodieldrin,  and tetra-
 chlorodibenzodioxin,  industrial chemicals such as PCB's and phthalate
 plasticizers,  important heavy organic chemicals, and of lead and
 cadmium [Kapoor et al.  (1970), (1971),  (1973); Hirwe et al.  (1972);
 Metcalf et al.  (1973  a,b,);  Metcalf and Lu  (1973); and Metcalf (1974b)] .
 This model ecosystem methodology has been widely imitated else-
 where and has been selected by the World  Health Organization as a
 standard  test method for evaluating the environmental impact of new
 candidate pesticides for vector control uses in aquatic  situations
 [Metcalf  (1974a)] .  The system is presently being used by the Illinois
 Natural History Survey to evaluate  the potential environmental impact
 of all new agricultural chemicals intended for use in Illinois.  In our
 laboratory, we have found  the model  ecosystem to be a valuable tool
 for basic  studies of the principles of  biodegradability using, the DDT-
 type compound as a model  [Kapoor et al. (1970),  (1971), (1973);
Metcalf et al. (1973); Metcalf (1974b); Coats et al. (1974)] .

      From these investigations it appears that this type of laboratory
model ecosystem has at least the following major uses:

      1.   Screening  of new candidate pesticides for environ-
          mental toxicity to a variety of organisms,  to
                                 66

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          determine pathways of enviroornental degradation,
          and to characterize quantitatively bioaccumulation
          and biodegradability.

      2.   Evaluation of the suitability of various pesticides
          for specific uses involving environmental contami-
          nation,  e.g., larvicides for application to streams,
          lakes, and reservoirs where fish culture is
          important.

      3.   Evaluation of the pollutant potential of various
          synthetic chemicals which may enter into the
          aquatic  environment as trace  contaminants from
          use or manufacturing effluent.
                             METHODS
      The model ecosystem technology has been fully described
[Metcalf et al. (1971); Metcalf (1974b)] .  The entire evaluation is
based about the use of radiolabeled molecules which permits tracing
the parent compound and its degradation products through the various
organisms and food chains of the system and the quantitative deter-
mination of the amounts stored in the various organisms.  Radio-
labeled degradation products are extracted from various organisms
of the model ecosystem, separated by thin-layer chromatography
(TLC) on  silica gel,  and visualized by radioautography on X-ray film
for 14C, 35S, or 32P- labeled compounds (Figure 1) or by serial
scintillation counting for ^H- labeled compounds.  The individual
components are then characterized both quantitatively by direct
liquid- scintillation counting and qualitatively by cochromatography
with known model compounds,  by appropriate microchemical reac-
tions,  and by infrared,  mass,  and nmr spectrometry.  The use of
silica gel containing fluorescent ZnS is especially helpful in visualiz-
ing the location of various model compounds on TLC chromatograms.
          and   p labeled compounds have been obtained from various
commercial suppliers, from the manufacturers of specific products,
or synthesized in  our laboratory.  A sample and inexpensive method
for ^H-labeling of aromatic  compounds [Hilton and O'Brien (1964)] ,
used in conjunction with the  SchSniger Oxygen Flask combustion tech-
nique [Kelly et al. (1961)] ,  has been very useful.
                                 67

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   BIODEGRADATION   OF
   IN   THE    MODEL    ECOSYSTEM
BIODEGRADATION   OF
IN   THE   MODEL   ECOSYSTEM
      "«H MOSQUITO STD  MML  WTCT WEN
                        -HYO
  oo,        i   •   9
  *•••»  nm MOMWTO sra   MM.  •mi
     FIGURE 1.  RADIOAUTOGRAMS OF TLC PLATES SHOWING
                  DEGRADATION OF TRICHLORO- AND PENTA-
                  CHLORO-BIPHENYLS IN LABORATORY MODEL
                  ECOSYSTEM
                  [ From Metcalf and Lu 1973)]
 Laboratory Model Ecosystem

      The system as developed after several years of study is shown
 in Figure 2.  It consists of a 25 x 30 x 45-cm glass  aquarium contain-
 ing a sloping shelf of washed white sand.   The lower portion is
 covered with 7. 1 of standard reference water [Freeman (1953)]  which
 provides satisfactory mineral nutriation for the growth of Sorghum
 vulgare  on the 15-cm flattened terrestrial portion, and for the fila-
 mentous alga Oedogonium cardiacum in the aquatic portion. The
 latter is seeded with a  complement of plankton (diatoms,  protozoa,
 rotifera), 30 Daphnia magna,  and 10 Physa snails.  The aquarium is
provided with aeration  and placed in an environmental plant growth
 chamber at 80°F (26°C) with 12-hour simulated daylight of 5000  ftc
(54, 000 lux). A Plexiglas cover,  28 x 30 cm covers the aquatic
portion of the chamber and reduces evaporation.
                                 68

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      FIGURE 2.  LABORATORY MODEL ECOSYSTEM USED IN
                  EARLY-WARNING STUDIES
                  [ From Metcalf et  al. (1972)]
      For operation of the model ecosystem 50 Sorghum seeds
(Pioneer 846) are planted in 5 rows on the flat terrestrial portion
and the aquarium allowed to equilibrate about 20 days  when the plants
are about 15 cm high. Radiolabeled pesticides for investigation are
typically applied  at 1 mg to 5 mg/chamber (0.2 to 1 Ib/A) dissolved
in about 0.3 ml of acetone and quantitatively applied to the leaves
with a capillary pipette.   As useful alternatives,  the radiolabeled
compound can be applied as  a seed treatment, as  a soil treatment
by injecting 50 x  5 ul amounts with a micrometer-driven  syringe,
pipetted directly  into the water  phase, applied as  a spray of aerosol,
or mixed with standard soils and incorporated into the sand  phase
                                 69

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 before planting the Sorghum.  All of these techniques have been used
 to give valuable information about distribution and fate of materials
 under test.

      At an appropriate interval after application, ten 4th instar
 Estigmene acrea larvae (salt marsh caterpillar) are placed in the
 aquarium  and allowed to feed on the Sorghum plants until these are
 consumed. The aquatic portion of the aquarium is subsequently con-
 taminated by fecal products of the caterpillars, by bits of leaf frasa,
 and by the bodies  of the caterpillars themselves - simulating natural
 channels of contaminant transport. The radiolabeled products enter
 various  food chains and after 26 days, 300 Culex quinquefasciatus
 mosquito larvae are  added, and after 30 days, three Gambusia
 affinis fish.  Typically, the experiment is terminated 33 days  after
 application of die  radiotracer,  when weighed samples  of fish,  snails,
 mosquito larvae,  algae, and water are removed and assayed for
 total radioactivity.  The samples are homogenized and extraced with
 acetonitrile and the concentrated extracts examined by TLC (Figure 1),
 The unextractable radioactivity from^the various substrates is deter-
 mined by combustion analysis in (he Schttniger oxygen flasks.
      Evaluation of Results.  A standard methodology has  been devel-
 oped to compare the  model ecosystem results for the various contam-
 inants.  The concentrations of total radiolabel and that of each of the
 components separable by TLC is determined in ppm.  These are
 arranged in standard tabular form to permit easy determination of
 two important parameters:  (1)  the ecological magnification (E.M.)
 or  ratio of concentration of parent radiolabeled compound  (or of any
 key degradation product) in fish,  snail, mosquito, daphnia, or alga to
 concentration in water; and (2) biodegradability index (B.I,), a numer-
 ical method for evaluating the relative biodegradability of  any candidate
 compound, defined as the ratio of radiolabeled polar compound to the
 radiolabeled non-polar compounds, in fish or other  organisms.  The
 data for determining this parameter are readily obtainable from TLC
 separations of the extracts, using a nonpolar solvent such as hexane
 or ether-hexane mixture.   The polar materials remain at  the origin
 while the non-polar compounds move  up the TLC plate as shown in
 Figure  1.  B.I.  values for  various compounds have  ranged from
 0.0001 to >1000 and examples are shown in Tables 1, 2 and 3.

      The unextractable radioactivity in the various  organisms is a
measure of total degradation of the test compound and has  varied from
as low as 0.1% for DOE to  as high as 60% for various highly degradable
                                 70

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        TABLE 1.  SUMMARY OF MODEL ECOSYSTEM EVALUATION OF 14C
                  POLYCHLORINATED BIPHENYLS
                  From Metcalf and Lu (1973)
2,5,2'-tri- 2,5,2',5'-tetra-
chlorobiphenyl chlorobiphenyl
Concentration in
fish, ppm 1.28 14.23
Unextractable radio-
activity, % 14.6 2.4
Ecological
magnification 6,400 11,863
Biodegradability
index 0.60 0.060
2, 5, 2', 4', 5 -penta-
chlorobiphenyl
119.70
1.1
12,153
0.019
    TABLE 2.  DEGRADATION OF 2, 3, 7,8-TETRACHLORODIBENZO-£-DIOXIN
               (TCBD) IN MODEL ECOSYSTEM
TCBD Equivalents, ppm
Oedogonium Daphnia
Total 14C
TCBD (RfO.62*)
Unknown
(Rf 0.06)
Polar (R{ 0. 0)
Unextractable
H2O
0.00144
0. 00034
0. 000039
0. 00036
0. 0007
(alga)
0.825
0.825
—
--
0.134
(daphnia)
1.338
1.256
--
—
—
Physa
(snail)
1.358
1.256
0. 0644 .
0. 0380
0.142
Culex
(mosquito)
1.895
1.837
--
--
0. 0578
Gambusia
(fi«h)
0.178
0.17
--
--
0.074
*TLC with hexane (Skellysolve B b.p. 60-68 C)
E.M. fish 500, snail 3694
B.I. fish 0.001, snail 0.029.
                                      71

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          TABLE 3.  DEGRADATION OF a-TRICHLOROMETHYL-£-ETHOXY
                   BENZYL-£-ETHO5$YANILINE IN MODEL ECOSYSTEM

                   From Hirwe et al. (1972)
Equivalents,
Oedogonlum Phyaa
H20 (alga) (a nail)
Total 3H
C2H5OC6H4NHCH (CC13 JCfcl^OCzHs
C2H5OC6H4NHCH(CCL3)C6H4OH
HOC6H4NHCH(CC13)C6H4OH
C2H5OC6H4C(O)CHCl2
C2H5OC6H4NH
C2H5OC6H4C(0)OH
Unknown (Rf 0.4)*
Polar (Rf 0. 0)
0.363
0.055
0.031
--
--
0.053
0.123
0.053
0.042
3.03
1.09
0.43
--
0.3
0.42
0.38
--
0.40
36.0
22.68
2.02
1.512
3.542
2.556
1.800
--
2.520
ppm
Culex '
(mosquito)
1.0
0.28
0.13
--
--
0.01
0.06
0.15
0.22

Gambusia
(fish)
0.30
0.041
0.081
0.03
0.028
0.03
0.03
--
0.060
 *TLC with ether-petroleum ether (b.p. 60-68 C) (1:1)
 E. M. snail 418, fish 0.75
 B.I. snail 0.075, fish 0.25

 compounds whose  radioactive-label becomes incorporated in the total
 metabolic pool.

      Degradative pathways describing the environmental fate of the
 test compound can be determined after identification of the majority
 of the key degradation products as shown in Figure 3.

      Environmental toxicity to any of the various organisms in the
 model system is easily observed,  and can be related to water con-
 centration of parent compound, as measured at intervals during the
 course  of the experiment. When all the organisms are killed as
 occurred with the  pesticide endrin which at 2 ppb killed all the fish,
these are restocked at intervals until survival  occurs, thus giving
an early warning of potential toxic hazard [ Metcalf et al. (1937b)].

      Other calculations which can be made include the. total biomass
concentration of test compound and its degradation products in each
of the organisms,  the rate of uptake  of radiolabeled  products from
water by the various organisms, and the nature of consecutive
                                   72

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                                   OH
                           *   603 It
                    CCI
          FIGURE 3. DEGRADATIVE PATHWAYS FOR a-
                     TRICHLOROMETHYL-p_-
                     ETHOXYBENZYL-£-ETHOXY-
                     ANILINE IN LABORATORY MODEL
                     ECOSYSTEM

                     [From Hirwe et al.(197Z)J
environmental reactions occurring in the water phase as determined
by TLC evaluation of the relative amounts of various products in the
water at regular intervals during the course  of the experiment.
                            RESULTS
Screening of New Candidate Pesticides

      The model ecosystem has been used extensively in our laboratory
to screen a variety of analogues of DDT for environmental degrada-
bility. These compounds were synthesized as part of a long term
                                 73

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 project to determine if it was feasible to produce insecticides which
 might be persistent on inert surfaces yet relatively biodegradable
 when absorbed by living organisms.  The basic methodology involved
 systematic study of the DDT molecule by replacing the environmentally
 stable  C-C1 bonds with other isosteric groups which could serve as
 degradophores by acting as substrates for the mixed function oxidases
 [ Metcalf et al. (1971), (1972)].  The action of the detoxifying enzymes
 on molecular moieties which could serve as substrates was shown to
 result in substantial changes in the polarity of the molecule so that
 the degradation products were excreted rather than stored in lipids as
 is the principal problem with DDT.  In order for candidate insecticidal
 compounds to have appropriate biological activity there is also a pre-
 cise requirement for molecular size and shape to be bioisosteric with
 DDT.

      The model ecosystem has been used to characterize the biodegrad-
 ability and degradation pathways of some of the most promising of
 these DDT-substitutes using ^H and ^C-radiolabeled  compounds
 [Kapoor et al. (1970),  (1971), (1973); Metcalf et al. (1971); Coats et al.
 (1974); Hirwe et al.  (1974)].

      The model ecosystem evaluation of the various DDT analogues
 producetd some interesting surprises as shown in Table 4.  Methoxychlor
 (R]=R2=CH3) and ethoxychlor (RjsR^C^sO) were substantially bio-
 degradable in fish but not in snail.  Their primary degradation was
 by O-dealkylation to  mono- and bis-phenols [Kapoor et al. (1970),
 (1971)].  Methylchlor (R1=R2=CH3) was highly biodegradable in fish
 but poorly degradable in the snail and was degraded by R-CH3 oxidation
 to mono- and bis-carboxy acids  [Kapoor et al. (1971)].  Methiochlor
 (RpR2=CH3S) was  the most readily degradable compound studied and
 was rapidly oxidized in vivo to a mixture of sulfoxide and sulfone
 derivatives [Kapoor  et al.  (1970)].  The compounds with asymmetric
 aryl substituents were  substantially degradable in fish and less  so in
 snail [Kapoor et al.  (1973)].   Chloro-methylchlor (Rj=Cl, R2=CH3)
 was intermediate in degradative behavior between DDT and me thy 1-
 chlor showing the importance of a  single degradaphore group in pro-
 moting excretion rather than lipid  storage.  Methyl ethoxychlor
 (Rj=CH3, R2=C2H5O)  was highly degradable in fish and was excreted
 through two pathways involving oxidation to car boxy lie acid and
 O-deethylation to phenol.

      Systematic examination of DDT analogues with altered aliphatic
moieties is still in progress.   However dianisyl neopentane
 (Rj=R2=CH3O, R3=C(CH3)3 a methoxychlor isostere was scarcely
anymore degradable than methoxychlor and was degraded very

                                   74

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           TABLE 4.  MODEL ECOSYSTEM CHARACTERIZATION OF
                     BIODEGRADABILITY OF DDT ANALOGUES^
»1
Cl
Cl
CH30
C2H50
CH3
CH3S
Cl
CH3
CH3O
CH30
Cl
R2
Cl
Cl
CH3O
C2H5O
CH3
CH3S
CH3
C2H50
CH3S
CH3O
Cl
•-' ' - - ^^^-
cci3
HCC12
CC13
CC13
CC13
CC13
CC13
cci3
cci3
C(CH3)3
HC(CH3)NO2
EM
Fish
84,500
83,500
1,545
1,536
140
5.5
1,400
400
310
1,636
125
;(b)

Snail
34,
8,
120,
97,
120,

21,
42,
3,
23,
500
250
000
645
270
300
000
000
400
000
33,231

EM
Fish
0.
0.
0.
2.
7.

3.
1.
2.
1.
7.
015
054
94
69
14
47
43
20
75
04
38
(0

Snail
0.
0.
0.
0.
0.
0.
2.
0.
045
24
13
39
08
77
0
25
105
0.
0.
23
034
       (a)  Data from Metcalf et al. (1971), Kapoor et al. (1973),
           Coats et al. (1974),  Hirwe et al. (1974).
       (b)  Ratio of concentration in organism/concentration in water.
       (c)  Ratio of polar/nonpolar metabolites.

largely through O-demethylation to mono- and bis-phenols rather than
by enzymatic attack on the neopentyl group [ Coats et al. (1974)]..
These neopentyl analogues have been suggested as non-chlorine sub-
stitutes for DDT and this kind of quantitative model ecosystem data
is a good example of the early  warning potentialities  of model eco-
system evaluation.

      Prolan® the nitropropyl analogue of DDT (R1=R2=C1,
RgsHQCH^NOo) showed surprisingly little concentration in fish and
was degraded exclusively through attack on the aliphatic moiety
largely by dehydronitrification and oxidation to 4,4* -dichlorodiphenyl
acetic acid [Hirwe et al. (1974)].   Thus it appears possible to produce
substantially degradable DDT-type analogues by altering only the
aliphatic moiety. From these  model ecosystem studies of DDT
analogues  it seems  apparent that there are a number of DDT-type

                                  75

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 compounds whose use is much more compatible with environmental
 quality than that of DDT itself.
 Suitability of Insecticides for Vector Control

       The World Health Organization (WHO) has the responsibility for
 technical guidance of control programs for vectors of human diseases.
 A new program is being developed in tropical Africa for the curbing
 of the filarial disease of humans,  onchocerciasis.  This disease
 caused by Onchocerca volvulus, affects more than 20 million people of
 whom 20% or more may become blind [WHO (1973)] because of the
 parasitic worms' invasion of the eye.  Onchocerciasis is transmitted
 between humans by the black flies Simulium which breed as larvae in
 running water.   Thus the  disease is concentrated along fertile river
 valleys and is increased with irrigation projects.  In an "all out"
 attack on this disease in the Volta River basin of West Africa, the use
 of DDT was first proposed as a Simulium larvicide.  Actually, DDT
 is not especially effective against black fly larvae and its wide use by
 aerial spraying is incompatible with environmental quality.  A WHO
 laboratory screening program  selected a number of candidate
 larvicides among which chlorpyrifos O, O-diethyl O-(3, 5, 6-trichloro-
 2-pyridyl) phosphorothionate (OMS 971 or Dursban®) was the most
 effective.  However the corresponding O, O-dimethyl ester (OMS 1155)
 was almost as effective as a larvicide and much less toxic to man and
 higher animals.  As part of the selection criteria,  the relative environ-
 mental degradability of the two esters was evaluated using 3, 5, 6-
 trichloro-2-pyridyl  -1^rC-2,6- labeled phosphorothionate esters in the
 model ecosystem.  The results [ Metcalf  (1974b)]  provided an excellent
 example of the utility of the model ecosystem as an early warning
 system.  The comparable values for chlorpyrifos  and chlorpyrifos
 methyl are shown below:

                              Chlorpyrifos     Chlorpyrifos Methyl

 Parent compound in fish,  ppm     0.0352              0..0076

 Unextractable 14C, %             23.9               52.2

 Ecological magnification          314                95

 Biodegradability index            1.02               3.95

      Chlorpyrifos methyl is evidently substantially more biodegradable
 and less accumulative in the fish,  Gambusia than chlorpyrifos.   On
the basis of its lower toxicity and higher biodegradability chlorpyrifos

                                   76

-------
methyl was selected as the more suitable larvacide for Simulium control
[Quellennec (1972)].  Comparison of the values above with those of
DDT and methoxychlor (Table 1) will indicate the importance of the
increased biodegradability of these organophosphorus insecticides.
Similar model ecosystems are being made with other pesticides
proposed for use in WHO programs.
Polychlorinated Biphenyls (PCB's)

      These industrial compounds have become almost as ubiquitous in
the environment as DDT and like DDT and DDE have been found to be
biomagnified in tissues of fish and other animals to levels as 10   fold.
These residues may pose a severe hazard to the  reproductive capaci-
ties of animals, e. g., mink,  and have been shown to cause teratogenesis
[ Envir.  Health Persps.. No. 1 (1972)].  The problems of PCB pollution
of the environment are  greatly complicated by the large number  of
individual chemical components of each industrial fraction, i. e.,
Arochlor 1242 (42% chlorine) has at least 30 isomeric chlorobiphenyls.
To make critical judgments of the severity of environmental effects
from these various compounds, these ^C-ring labeled chlorinated
biphenyls were evaluated in the model ecosystem [ Metcalf and Lu
(1973)]. A summary of the results  is given in Table  1.

      The model ecosystem results  clearly show that the environmental
hazard increases with the number of chlorine atoms in the biphenyl
nucleus  and that the biphenyls containing higher percentages of chlorine
may be expected to persist longer in nature and to accumulate to higher
levels.
Endrin

      The use of 14C-ring labeled endrin or 1,2,3,4, 10, 10-hexachloro-
6, 7-epoxy-l, 4,4a, 5, 6, 7, 8, 8a-octohydro 1, 4-endo, endo-5, 8-dimeth-
anonaphthalene (2.3 m Ci/mmole) in the model ecosystem provided a
good example of early-warning potentialities.  Endrin was applied at
 1. 0 mg (0. 2 Ib/A) or 0. 2 the usual application rate in model ecosystem
investigations.  Biological observations of the organisms in the
system were particularly informative.  The compound was highly toxic
to the salt marsh caterpillar even at the  reduced dosage.  As the
level of contamination in the water rose to 0. 06 ppm the Daphnia and
Culex'larvae were repeatedly killed and had to be reintroduced.  The
water phase was incredibly toxic to Gambusia developed violent
convulsions within a few minutes of being placed in the aquarium and

                                  77

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 died within a few hours.   This water toxicity persisted for more than
 60 days from the beginning of the experiment and was associated with
 water concentrations of endrin from 1-2 ppb.   This toxicity delayed  ,
 the termination of the experiment for twice the usual 33 day period
 and provided a striking parallel to the Mississippi  River fish kills
 associated with endrin wastes [ Barthel et al.  (1969)].  Thus this
 experiment demonstrated the predictive value of the biological
 observations.

      At the conclusion of the experiment,  endrin was present in the
 organisms of the system: Oedogonium 11.56 ppm (84. 9% total * C),
 Physa  125. 0 ppm (82. 8%), and Gambusia 3. 40  ppm (75. 8%).   The
 degradation products were apparently heto- and hydroxy- derivatives.
 The E.M. values were fish  1335 and snail  49,218,  and the B.I.  values
 were fish 0. 009  and snail 0. 0124 [ Metcalf  et al.  (1973)].
 TCBD
       This compound 2, 3, 7, 8-tetrachlorodibenzo-j>-dioxin (ring UL-
      o. 64 in Ci/mmole) was foutid to be highly persistent in the model
 ecosystem as shown in Table 2 [Metcalf et al. (1974)1.  The intact
 TCBD comprised from 93 to 99% of the extractable 1^C in the various
 organisms, with only traces of an unknown degradation product
 (Rf 0. 06) appearing in the snail and in the water.  At the  conclusion of
 the experiment, the  TCBD level in the water was 0. 34 ppb or at the
 water solubility level.  The  E.M. values ranged from 500 in fish to
 5574 in Culex larvae, and the B. I. values from about 0. 001 in fish
 to 0. 08 in snail (Table 2).  These model ecosystem data together
 with the extreme toxicity and teratogenicity of TCBD (Envir. Health
 Persp. No. 5, 1973) and its metabolic stability (Vinopal and Casida
 1973) give strong early warning signals that this toxic impurity formed
 in the manufacture of chlorinated phenols cannot be tolerated as an
 environmental pollutant  in any detectable amounts.
An Environmental Unknown

      To explore further the value of the model ecosystem technology
as an early warning, we will consider an environmental unknown, a
potential new candidate insecticide a-trichloromethyl-p_-ethoxy-
benzyl-p-ethoxyaniline (HLrwe et al., 1972).   This compound was
3H-ring labeled at  1.2 mCi/mmole and evaluated in the model ecosys-
tem in the  usual manner with the results shown in Table 3.   The  com-
pound is degraded to more polar metabolites by O-dealkylation to

                                  78

-------
form mono- and bis-phenols.  It also undergoes a dehydrochlorination
followed by a tautomeric shift to an unstable intermediate a-dichloro-
methyl-£-ethoxybenzylidine-p_-ethoxyaniline which is cleaved to j>-
ethoxyaniline and p_-ethoxydichloro-acetophenone.  (Figure 3).  The
latter, identified by mass spectrometry, is further degraded to p_-
ethoxybenzoic acid.  Other products which must form but were not
identified are the easily conjugated p_-hydroxyaniline and jj-hydroxy-
benzoic acid.  The parent compound was substantially concentrated in
the snail, E.M. 418,  but not in the fish, E.M. 0.75.  The values for
B.I. were snail 0.075 and fish 0.25.  However, these depend on  the
definition of polar metabolites and the values given represent a con-
servative view.   From this evidence, the reader may draw his own
conclusions about the potential effects of this compound on environmental
quality.
                       ACKNOWLEDGMENTS
      The research reviewed in this presentation was supported in part
by grants from the Herman Frasch Foundation, The Rockefeller
Foundation, the U. S.  Department of Interior and University of Illinois
Water Resources Center Project B-OSO-ILL, the U.  S. Environmental
Protection Agency, EP-R-802022,  and the National Science  Foundation.
                           REFERENCES
Barthel, W.F., J. C. Hawthorne,  J.  H.  Ford, G. C.  Bolton, L.  L.
McDowell, E. H.  Grissinger,  and D.  A.  Parsons, Pest. Monit. J.,
3, 8 (1969).

Coats, J., R. L.  Metcalf, and I. P. Kapoor,  Pesticide Biochem.
Physiol. (1974).

Freeman,  L., Sewage Ind.  Wastes, 25, 845,  1331 (1953).

Hilton,  B. D., and R. D. O'Brien.  J. Agr.  Food C hem.,  lj£, 236
(1964).

Hirwe,  A. S., R. L. Metcalf, and I.  P.  Kapoor, J.  Agr.  Food Chem.,
20, 818 (1972).


                                  79

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Hirwe,  A. S. ,  R. L. Metcalf,  and Po- Yung Lu.  In preparation (1974).

Kapoor, I. P. , R.  L.  Metcalf, A.  S.  Hirwe,  J. R. Coats, and M.' S.
Khalsa,  J. Agr.  Food Chem. , _2^ 310 (1973).
Kapoor, I. P., R.  L.  Metcalf, A. S. Hirwe,  Po-Yung Lu, J. R. Coats,
and R.  F.  Nystrom. ,  J. Agr. Food Chem. , 20,  1 (1972).

Kapoor, I. P. , R.  L.  Metcalf, R. F. Nystrom,  and G. K. Sangha,
J. Agr.  Food Chem.,  1JJ,  1145 (1970).

Kelly, R. G. , E. A. Peets,  S. Gordon, and D.  A.  Buyske, Ann.
Biochem. , 2, 267 (1961).

Metcalf, R.  L. , Proc. Symposium on Use of Radioisotopes in Study
of Environmental Contamination, FAO, IAEA, WHO,  Helsinki, 1973.
In Press (1974a).

Metcalf, R.  L. Essays in Toxicology, 5_, 17 (1974b).

Metcalf, R.  L, G.  M. Booth, C. K. Schuth, D.  J.  Hansen, and Po-
Yung Lu, Envir.  Health Perspectives (1973a), June, p 27.

Metcalf, R.  L. , I.  P. Kapoor, and A. S. Hirwe, Chem. Tech. , _2_
(2),  105 (1972).

Metcalf, R.  L. , and Po-Yung Lu, "Environmental Distribution and
Metabolic Fate of Key Industrial  Pollutants and Pesticides in a
Model Ecosystem", University of Illinois Water Resources Center,
UILU-WRC-0069 (1973).

Metcalf, R.  L. , I.  P. Kapoor, Po-Yung Lu, C. K. Schuth, and P.
Sherman, Envir. Health Perspectives (1973b), June,  p 35.

Quellennec, G. Bull. World Health Org. , J6,  227 (1972).

Vinopal, J.  H. ,  and J. E.  Casida.  Arch. Envir. Contam. Toxic ol. ,
1, 122 (1973).
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      METHODS FOR DETECTION OF TERATOGENIC AGENTS
           T.  H.  Shepard, Allan Fantel, and Ted Regimbal
                       University of Washington
                         Seattle, Washington
                            ABSTRACT
      Current methods used for detection of teratogenic agents consist
of three defense systems:  (1)-animal teoting and prediction from
chemical structure, (2) in vitro testing by tissue culture,  organ
culture, or whole embryo culture,  and (3) monitoring at the fetal, new
born and later periods.  Since experience  shows that all too often the
last of the  three defenses, the monitoring  systems, must be used,
there is an urgent need to make the testing systems more reliable.
                                   81

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               THE WORLD HEALTH ORGANIZATION'S
             ENVIRONMENTAL HEALTH CRITERIA AND
                    AIR MONITORING PROGRAMS

             Dr. F. Gordon Hueter,  Dr.  S.  David Shearer,
                        Mr. Gerald  G. Akland
                      World Health Organization
       International Reference Center for Air Pollution Control
                  Office of Research and Development
               National Environmental Research Center
               Research Triangle Park,  North Carolina
                           INTRODUCTION
      The World Health Organization is the intergovernmental organi-
zation of the UN system dealing with health.  WHO was established in
1948; it now has 135 member states, whose constitutional bodies are
the World Health Assembly, which meets once every year,  and the
Executive Board.  The Organization is headed by the Director General,
who is  elected by the World Health Assembly.  It has its headquarters
in Geneva and has  six Regional offices,  namely, in Washington, D. C.
for the Americas (united with the Pan-American Health Organization),
in Copenhagen for  Europe, in Brazzaville for Africa, in Alexandria
for the Middle East, in New Delhi for Southeast Asia, and in Manila
for the Western Pacific.   Its total staff is about 5, 000 people  and its
working budget in  1973 was just over U. S.  $90 million.

      The objective of WHO is the attainment by all people of  the
highest possible level of health.

      It should be clearly understood that WHO functions largely as an
advisory body.

      Concern over the human environment is a constitutional function
of the World Health Organization.  Enviornmental health was  therefore
one of the five priorities established for  WHO's program of work at
the First.World Health Assembly in 1948.  Following an in-depth
review, the Twenty-fourth World Health  Assembly in 1971  adopted as
part of its fifth General Program of Work for the specific period from
1973-1977,  inclusive, that the promotion of environmental health re-
main one of the principal program objectives of the Organization next
                                  82

-------
to the strengthening of health services, the development of health
manpower,  and disease prevention and control.  The program
includes assistance to countries for: the provision of basic sanitary
services as a continuing activity for the control of communicable
diseases; the control of environmental pollution and nuisances as a
means of protecting health and ov avoiding disturbances in the
ecological systems; the improvement of environmental conditions in
urban and industrial areas; and the  provision of the necessary
infrastructure, including manpower, to carry out effective environ-
mental health programs.  It should  generate technical information
regarding environmental health conditions, such as maximal per-
missable levels of pollutants in air, water, soil,  and food,  and
should assist countries in developing national systems for gathering
such information and for determining when and where preventive
action is required.  This should facilitate the formulation of
environmental health criteria in relation to food technology,
pollution, environmental radiation,  noise and other nuisances, and
to occupational exposure of workers, as  a basis for the establishment
of national standards.

      As the International Reference Center for Air Pollution Control
of the WHO, the NERC/RTP is directly participating in and providing
the lead role for the WHO Environmental Criteria Program and  Air
Monitoring  Program.
      WHO ENVIRONMENTAL HEALTH CRITERIA PROGRAM
      WHO defines environmental health criteria as the quantitative
relations between the exposure to a pollutant and the risk or mag-
nitude of an undesirable effect under specified circumstances defined
by environmental variables and target variables.  In WHO's view,
environmental health criteria are basic tools  for action against
pollution, for the planning of programs,  for the setting of national
standards, and for the  evaluation of environmental programs.

      It  should be made clear that WHO environmental health criteria
are essentially scientific information which are hoped to become
input into national endeavors.   In other words, it is not WHO policy
to develop universal derived working limits, universal air quality
standards, etcetera.  They do believe,  however,  in the universality
of scientific  information.  Therefore, the prime objective  of the
WHO environmental health criteria program is to promote agreement

                                 83

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among the scientists on scientific information related to the quantitative
relations  between exposure to pollutants and the risks and on accepted
maximum levels of a pollutant in the organism or the population.

      Environmental health criteria pollutants were prioritized on the
basis of:  the severity of adverse effects on the population; the per-
sistence of the agent in the environment; metabolic degradation or
synthesis in biological systems; the ubiquity and abundance of the
agents in man's environment; the size,  type, and demographic
characteristics of the population exposed as well as work done in the
past; the feasibility of control and prevention; the degree of control
that already exists; the extent of knowledge available; and many other
considerations.

      Obviously, any ordering of priorities will receive continuous
review.  Notwithstanding, however, there  was agreement that an
initial series of environmental factors be considered for immediate
examination,  namely:

      1.   Oxides of nitrogen (NO ), because of their  unclear public
          health implications in the ambient air;

      2.   Mycotoxins, because of their  possible contribution to
          chronic disease, including cancer, especially in the
          largely agricultural countries with warm and damp
          climates;

      3.   Nitrates and nitrites, because of the  possibility of
          ultimate conversion to nitrosamines in man, and the
          use of nitrates in agriculture and of nitrites in food;

      4.   Manganese,  because of its demonstrated neutrotoxicity
          and the possibility of its  becoming more widely
          disseminated primarily as a  fuel additive;

      5.   Polychlorinated biphenyls (PCBs),  because of their
          demonstrated persistance, toxicity and wide
          dissemination in water,  packaging material and
          paints;

      6.  Asbestos,  because of its demonstrated carcinogenic
          properties and widespread use for industrial, structural
          and other commercial purposes.
                                84

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      What now is the machinery which WHO apply in establishing
environmental health criteria?

      Three different procedures  are envisaged:

      A.  Preparation of new criteria documents.  This will be
          carried out in three stages:

          (i)  Preparation of an outline for national contributions
              and preparation of national contributions.

          (ii)  Consolidation of national contributions into draft
              criteria documents.  This will be done on sub-
              contract either to individual experts or to WHO
              Collaborating Institutions.

         (iii)  Review of the draft by task groups of international
              experts.

      The total time estimated for the preparation of such documents
is about 18 months from the moment the outlines are circulated to
national institutions.

      B.  Preparation of criteria documents based on existing
          documentation.   This approach will be used  where
          criteria-like  documents (either WHO or national)
          already exist.  The following stages are envisaged:

          (i)  Preparation of a draft criteria document based
              on an outline established by the WHO secretariat.
              This work will be done on a contract with recognized
              experts.

          (ii)   Circulation of the draft document to national
               institutions for comments and additions.

          (iii)  Revision  of the draft document based on national
              comments.   This will be done as a part  of the
              contract under (i).

          (iv)  Review of the final draft document by task groups
               of international experts.  Total estimated time for
              for the preparation of a document is 12 to 14 months.
                                   85

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      C.  Preliminary reviews.  As recommended by the Secretary
          General's Report, a short-cut procedure is envisaged
          consisting only of two stages:

          (i)  Preparation of a draft preliminary review according
              to an outline established by the WHO secretariat.
              This will be done on contract with recognized experts
              in the field.

          (ii)  Review of this draft by task groups of inter-
              national experts.  Estimated time for the
              preparation of a preliminary review is 6 to 8
              months.

      The environmental pollutants scheduled for consideration
during the period 1973-1975 are listed in Table 1 according to the
respective procedural approach.

        TABLE  1.  ENVIRONMENTAL HEALTH CRITERIA
                   POLLUTANTS PROCEDURE

Group        ABC
        Mn;              Cd; Hg; Pb; NQx;     Sb; Bi; Se; Mo; Te;
          Nitrates,         asbestos             Ti; Ge; Sn;
          nitrites,                              Organic dusts;
 I        nitrosamines;                         Petroleum Pro-
          PCBs;                                 ducts
          Mycotoxins


        Ni; V;            As; Be; Cr;           Li; Ba; La; Al;
          Sulfates-H^SO^    SO£ and suspended  Ga; Zn; Fe; Ni;
          aerosols;          particulate matter;  Co; Pd; Pt; Inert
II        Fluorides;        CO; Ozone and       dusts; Plastics
          Chlorinated       oxidants; poly cyclic
          bioacides  and     hydrocarbons
          chlorine
                                 86

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                WHO AIR MONITORING PROGRAM
         The WHO program to assist Member Countries in
establishing, developing, and operating air pollution monitoring
networks was initiated toward the end of 1967.  The program is
implemented through the WHO reference centers and collaborating
laboratories on air pollution, which include,  at present, two
International Reference  Centers (IRC),  the IRC for Clinical and
Epidemiological Aspects of Air Pollution at the Medical Research
Council's Air Pollution Unit, St. Bartholomew's Hospital Medical
College, London; and the IRC on Air Pollution Control at the
Environmental Protection Agency, Washington,  D. C., United States
of America.  In addition, there are three regional reference  centers
at Moscow, Nagpur,  and Tokyo; seven national reference centers
and eleven collaborating laboratories; plus laboratories in 19 cities
in the Pan American Sampling Network.

         One of the main functions of the reference centers and
collaborating laboratories is to promote the use of uniform methods
of measurement; to introduce reliable and effective procedures for
the calibration of routine sampling and  analytical methods; to improve
the quality of monitoring systems; and to standardize the handling,
statistical analysis, and use of data. This program will also help in
generating internationally comparable data on levels  and trends of
air pollution in some urban and industrial areas; these comparable
data may help in identifying patterns of exposure to air pollution;
may facilitate the planning and assessment of health effects  studies
carried out in different  countries; and may facilitate  the compara-
tive evaluation of the effectiveness of national air pollution control
programs--to mention only  some of the uses of such information.

         As a part of the program,  a number of monographs  on the
measurement of common air pollutants have been prepared and
distributed to the collaborating laboratories  and national reference
centers for use and comments.

         WHO recently initiated a pilot  study to  evaluate and  test a
scheme for handling and statistically analyzing air pollution data.
Forty-eight sites located within 16 countries are involved in this
pilot study.  The pollutants  monitored in the study are confined to
SO2 and suspended particulate matter.  Each country selected three
sites within a major city, one from each of the three categories,
                                 87

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 "inner city - commercial", "inner city - industrial",  and "sub-
 urban -  residential",  in order to be representative of existing
 concentrations throughout the city.

      The countries that agreed to participate in this activity are:
 Austria, Belgium, Canada, Czechoslovakia, Federal Republic of
 Germany, India, Israel, Italy,  Japan, The Netherlands,  Spain,
 Sweden, United Kingdom,  USSR, Yogoslavia, and the United States.

      It  was recently  recommended at a joint meeting that the
 monitoring network operations be expanded to:

      a.  Increase the number of sampling stations per
          country up to 8;                          '

      b.  Increase the number of countries to 30; and

      c.  Increase the number of pollutants measured. The
          next pollutant for consideration would be ozone.
    WHO ENVIRONMENTAL HEALTH MONITORING PROGRAM
                           Introduction
      The United Nations Conference on the Human Environment
(Stockholm,  1972) adopted several recommendations  (Nos.  71, 73,
77, 78, and 82) that directed WHO and other international organiza-
tions to develop programs for monitoring the levels of pollutants in
air, food and water and to use the information derived from such
activities, and from other sources, to develop criteria and standards
for the protection of human health.  In fact, monitoring activities
recommended by the Stockholm Conference are  part of a  comprehen-
sive Earthwatch program, the function of which will be (a) mon-
itoring, (b) evaluation of,  (c) research, and (d)  exchange of infor-
mation on the state of the environment as a basis for rational environ-
mental management decisions,  and for an early warning of possible
major effects harmful to man's health and well-being.
                                88

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      The objectives of the proposed program are:

      1.  To strengthen national environmental and health
         monitoring systems and

      2.  To provide an international information synthesis on
         trends and levels of environmental quality and its
         effects on man's health and well-being,  based on
         selected data provided by national monitoring
         systems.
                           Priorities
      1.  Technical assistance

         The provision of technical assistance to national
         monitoring systems is the major component of
         the program.

      2.  International Information synthesis

         An international synthesis of environmental health
         data supplied by national monitoring systems can be
         attempted only if such data are comparable and if
         the monitoring systems are designed so as to enable
         a meaningful interpretation of data.

      A computerized inventory will have to be maintained of
relevant national activities and of environmental health data avail-
able, and of those factors that may be important in'interpreting the
data.

      It is envisaged that international information synthesis will be
provided for

      a.  Trends and levels of air quality in urban areas

      b.  Selected parameters of water quality in some international
          river and coastal waters

      c.  Selected parameters of food quality
                                  89

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d.  Epidemic logical studies on environmental health effects

e.  Changes in mortality and morbidity data that may be
    related to environmental influences, and of other
    selected environmental health indicators.

3.  Environmental monitoring

    Although it is accepted that priorities may vary from
    one country to another,  the selection of environmental
    factors to be monitored must be based on an agreed
    set of criteria. Considerations that need to be taken
    into account when establishing priorities are the same
    as for the pollutants mentioned earlier.

    It has to be  recognized that some of the prioritized agents
    will not satisfy all of the criteria in every country.  It is
    apparent that while many would be of particular importance
    to the developed countries wthe problems of developing
    countries may differ.  Therefore, it may not prove
    practicable  to include all of the measurable priority
    environmental agents in the initial phase of the inter-
    national environmental health monitoring program.

Elements of the program are

1.  Comparability of measurements and data quality control

2.  Design and operation of monitoring networks

3.  Data acquisition and analysis

4.  Emergency  response teams

5.  Training and fellowship programs and

6.  Research and Development through international
    coordination.
                          90

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     Specific program areas would address

       1.  Air Quality

       2.  Water Quality
             a.  Inland water bodies
             b.  Coastal waters
             c.  Drinking water supplies

       3.  Food Contamination

       4.  Occupational and Home Exposures

       5.  Integrated Monitoring Systems

       6.  Environmental Radiation and Other Physical Factors

       7.  Monitoring of Health Effects
             a.  Routine data
             b.  Health indicators
             c.  Special surveys


                  Health Early-Warning System
      The establishment of a health surveillance system which would
provide an early-warning of adverse environmental effects is an
extremely difficult program area and should be considered as a part
of a much wider program on early warning systems of significant
changes in the health status of the community.

      An adequate warning system in WHO's opinion must be
characterized by four mutually supporting program activities: first,
epidemiologic studies to detect the first significant changes in the
frequency or tempro-spatial distribution of selected health events;
second, an integrated environmental monitoring system that can
signal environmental changes perhaps several decades before the
health effects become manifest; third, development of generalized
and specific human exposure models so that range estimates  of
human exposures can quickly link environmental monitoring data to
primary and secondary health data sources for effects studies; and
fourth, the ability to activate appropriate toxicologic and clinical
testing systems which can determine the biological plausibility and


                                 91

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coherence of the suspected adverse effects.  The components of the
above system could also be used to document the beneficial health
effects of different environmental control strategies.
                                 92

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                A COST-RISK-BENEFIT ANALYSIS
                     OF TOXIC SUBSTANCES

                       Dennis P. Tihansky
                   Economic Analysis Branch
                          Harold Kibby
                    Ecological Studies Branch
            Washington Environmental Research Center
              U. S. Environmental Protection Agency
                       Washington, D. C.
                           ABSTRACT
      Hundreds of new toxic substances are produced each year to sat-
isfy consumer demand, but many of them also enter the environment
as risks to the exposed population and to ecosystems.  The most  logi-
cal criterion for their control is a net comparison of all product gains
and risk losses from using these  substances, with the objective of
maximizing the overall welfare of society.  The operational frame-
work  presented here attempts to synthesize cost-benefit and risk
information into a decision-making setting  for the purpose of identify-
ing the optimal control level.  Both quantitative and qualitative value
systems are merged into.a single framework, and sequential stages of
the analysis are outlined in detail.  Several decision-making approaches
are recommended, the appropriate choice depending upon the extent of
risk-benefit data available as well as the preference for monetary
versus nonmonetary values.  Uncertainty in the data base complicates
the assessment since its inclusion requires the application of special
statistical measures of confidence.
                         INTRODUCTION
      As a result of rapid technological changes and industrial develop-
ment, a large and increasing number of toxic and hazardous sub-
stances enters the environment or appears in consumer products each
year.  Because so many of these elements are generated without
stringent regulations,  or perhaps with no controls at all, man and
nature have been involuntarily exposed to their effects.  Some toxic
                                 93

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 substances cause known potential hazards to human health or ecologi-
 cal habitats, but the majority is not well understood and thus intro-
 duces uncertain risks to the environment.

      In view of these informational deficiencies, policymakers face
 the complex task of setting optimal standards on product content and
 environmental quality.  This problem becomes particularly acute with
 early warning systems, designed to recognize potential dangers from
 harmful chemicals and organisms.  The limited  time horizon for early
 warning precludes an extensive, detailed analysis of risks and benefits.
 Yet regulation, to be effective over the long run, cannot rest simply
 on intuitive decisions or arbitrary preferences.  Inherent values and
 needs of society must be identified and,  if possible, quantified in a
 framework that reveals the major welfare impacts of regulation.
 There is consequently a need  for the development of methods to assess
 the cost-risk-benefit trade-offs of alternative decisions.

      In the National Academy of Engineering's colloquium on benefit-
 risk perspectives, LindU) emphasized the importance  of quantitative
 approaches.  He was "disturbed by the absence of an understanding of
 the basis principles and methodology of decision analysis and benefit-
 cost analysis... ".  He further stated, "Some people will contend that
 it is impossible to quantify the outcomes of many social programs.
 To this I would answer that without quantification of the most basic
 nature it is impossible to specify a rational criterion for the evalua-
 tion of any program".

      Echoing this observation,  the President's Science Advisory
 Committee I2) argued that the  absence of quantitative information is
 likely to bias regulations toward the overprotection of health and
 ecology.  While risk avoidance is  a necessary consideration, its value
 to society  should be contrasted with that of products generating or
 containing toxic elements.  The cost of incomplete information  could
 have serious outcomes, as the Committee  recognized:  "Regulatory
 decisions in the name of protection of health and  environmental integ-
 rity often have expensive consequences.  They typically obligate large
 expenditures of money, they are meant to remain in effect over long
 periods of time,  and they typically rearrange large areas of our lives.
 Given the large impact of these consequences, the decisions producing
 them deserve the  best foundation possible.  Errors in regulatory
judgments  can be  extraordinarily expensive, in human and monetary
terms. "
                                 94

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      This study presents a conceptual framework for a cost-risk-
benefit analysis, hereafter called a CRB analysis.  Operational stages
of analysis are identified as they contribute to the optimal decision of
maximizing social welfare.  The utilitarian value of the method is
limited by inadequacy of data,  particularly on the risks  from toxic
substances.  However, a methodological framework is important even
prior to application.  By outlining data requirements, it results in the
selective  processing  of information. Otherwise,  the decision-maker
could become enmeshed in an unmanageable,  largely valueless data
bank.

      Traditional cost-benefit analysis translates all impacts into
economic magnitudes.  Obviously, the  use of a common denominator,
such as the  current dollar value,  simplifies the task of selecting that
control level at which toxic substances yield the highest net benefits to
society.   Unfortunately, many risks and benefits  cannot be easily
quantified in economic terms.

      Muellhause(3),  for example, claims that risks cannot be  valued
simply as the product of their cost times the  probability of their
occurrence.  There is also a "nonpecuniary type  of boundary condition",
which governs the behavior of populations at risk. A much broader
concept than that of the traditional analysis is thus recommended.  The
framework presented here can apply to either conceptual approach — the
pure economic or the more comprehensive analysis.
                   CONCEPTUAL FRAMEWORK
      The term,  cost-risk-benefit analysis, implies that decisions on
toxic substances  are based on some sort of accounting scheme of
desirable versus undesirable outcomes.  Almost every decision in-
volves elements of risk in addition to benefits,  and their assessment
is often subjective and based on uncertainties.  At the national level,
an error of judgment can have  serious  repercussions, in the future if
not at present.  The outcome can affect a large segment of society and
can disrupt or perturb economic growth. Notably in the protection of
health and safety, the public  is demanding more than ever that strong
legislation be enacted to enhance the overall welfare of society.  With
hundreds of new toxic chemicals manufactured  each year, this demand
becomes more challenging.  As a result, legislators  are confronted
with the difficult evaluation of risks and damages (both immediate  and
probable) and balancing them against social benefits of using toxic
substances.

                                 95

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      Risk-benefit assessments have evolved into a comprehensive,
 systems framework in order to compare a variety of welfare trade-
 offs.^4' To develop and utilize this framework requires naultidisciplin-
 ary expertise.  Economists have contributed methods and theory for
 the measurement of social welfare impacts based on market prices or
 personal willingness-to-pay. (5) Statisticians have derived confidence
 intervals and other probabilistic measures to assess the degree of risk
 or benefit uncertainty. (°> ?)  Ecologists and health experts have con-
 ducted various experiments and research to test animal (and less
 frequently human) responses to specific toxic materials. (2, 8)  But
 most of these tests have been confined to acute,  rather than low-level
 or long-run, exposures.  To utilize this information on risks and bene-
 fits, operations research analysts have devised methods of determining
 socially optimal decisions  for toxic and other substances. Some of these
 techniques  are designed especially to handle risk uncertainty, e. g.,
 see  Reference (9).

      Figure 1 abstracts the operational framework for an evaluation of
 environmental quality.  Although the analysis pertains to the control of
 toxic substances, it can be generalized to other objectives, such as the
 assessment of competing energy sources. Both economic and non-
 economic factors are represented.  Product and service benefits can
 usually be measured in monetary units.  But many social and ecological
 risks defy quantification and currently are not well understood.  To
 neglect the latter effects in a CRB analysis would yield a partial, and
 probably misleading,  solution of welfare optimization.

      According to this diagram, the analysis of toxic substance con-
 trols is delineated into three components.  First, the cost-benefit
 assessment pertains to net economic losses  attributable to changing
 consumer demand and supply for products or services subject to
 controls.  Costs can include the treatment of toxic effluents,  the sub-
 stitution of nontoxic for toxic products, and process modifications to
 alter toxic input requirements or product composition.  Benefits
 respond to each person's willingness-to-pay for the consumption or
 use of items containing toxic substances or generating them as  waste
 residuals.   Net benefit losses can be expected when productive
 resources  are  shifted from manufacturing or service sectors into
 toxicity control programs.

      Less  amenable to monetary evaluation are risks to human health
 and ecological  systems.  The risk analysis attempts to translate these
 probabilistic states, wherever possible, into expected damages or
welfare losses.  For some risk categories,  quantification is  currently
infeasible.  By controlling toxic substances, risks are avoided, thereby

                                  96

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 PRODUCT AND SERVICE
COST-BENEFIT ANALYSIS
HEALTH AND ECOLOGY
   RISK ANALYSIS
                  OPTIMAL CONTROL LEVEL
                      DECISION-MAKING
  FIGURE 1.  BROAD CONCEPTUAL FRAMEWORK FOR
              IMPACT ANALYSIS OF TOXIC SUBSTANCE
              CONTROLS
                            97

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 enhancing the safety and welfare of society and preserving environ-
 mental amenities.

       Both the cost-benefit and risk analyses provide input data for the
 decision-making component.  Here, economic and ecological conse-
 quences of various toxicity control levels are compared, and the best
 solution is found via one of several optimization techniques.  The
 choice of a technique to identify this level is influenced by the type and
 extent of available benefit-risk information.  In the case of early warn-
 ing systems,  only a shortened version of the complete CRB evaluation
 is feasible because of time constraints on the collection and analysis
 of data.
                     COST-BENEFIT ANALYSIS
       The operational elements of a cost-benefit analysis are outlined
 in Figure 2.  Arrows in the diagram portray the flow of information
 among sequential steps.  The first step entails the preselection of all
 benefit categories, a^, a^, . . . , which depend on the direct or indirect
 utilization and consumption of toxic substances. An example is  the
 demand for pulp and paper, whose production generates mercury-
 containing residuals. Effluent  controls on these residuals could be so
 stringent as to aggravate price hikes.  Increased costs of control are
 thus eventually passed on to the consumer, who disbenefits either by
 paying more per unit of product or by discontinuing his purchase.

       For increasing control levels,  C,, €2, . . . , as defined in Step 2,
 prices respond in corresponding fashion. Step 3 depicts a typical con-
 sumer response, also illustrated in more detail in Figure 3. At con-
 trol level  Cj, the price of product (or service) otj is Pia; while at £>-£
 it becomes
      A price hike ordinarily implies welfare losses to the consumer
of that  product.  This impact is derived in Step 4 (of Figure 2).  As
shown more fully in Figure 4, the equilibrium price moves up the
demand curve with increasing controls.   From welfare economic
theory, total benefits are measured as the area under this curve but
above the price line.   That is,  benefits  to each consumer equal the
difference between the actual price and what he is willing to pay.
Some individuals  will pay as much as  U, while marginal consumers
will pay no more than the current price  Pja.  If the unit price in-
creases to P2a» the marginal consumer  (at PIO.) is  no longer willing
to buy the product or service.  Benefit losses  from  decreased demand
                                98

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               PRODUCT AND SERVICE
              COST-BENEFIT ANALYSIS
                   1 )  BENEFIT PORTFOLIO

                        ct = «lf a2, ...


                       CONTROL LEVELS  .

                        C = Ci» Up» ...


                       CONTROL COST IMPACT
               	(4)  BENEFIT VS. CONTROL
                       MONETARY BENEFIT CURVE
                         J.

                       WILLINGNESS-TO-PAY
                         FOR ALL BENEFITS
FIGURE 2. SEQUENTIAL STAGES OF COST-BENEFIT ANALYSIS
                           99

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8
1
I  i
U  TJ
I  ~
                 Cl         C2

                  INCREASING CONTROLS


                (e.g., percent removal)
Ul  *-»
O   W»
l-l   (.
QC   *
a.  §—
  FIGURE 3.  IMPACT OF VARIOUS CONTROL LEVELS

              ON PRODUCT OR SERVICE PRICES
                           100

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                              Total benefits
                                    Area  = B
                                           la
                              DEMAND
                          (total units)
FIGURE 4. ESTIMATION OF PRODUCT OR SERVICE BENEFITS
           FOR VARIOUS CONTROL LEVELS
                              101

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 are then estimated by the area, XPlaP2a«  Additional disbenefits are
 incurred by the remaining consumers, who pay an additional Pja ~
 per unit.  Welfare losses for these individuals equal the rectangular
 area, XYZP2a.  Total disbenefits to society are thus estimated as
       These losses are based not on the direct use of toxic substances,
 but rather on their effect on the price of directly consumable items.
 Provenzano(lO) argued similarly that the value -in -use of such inputs
 can be measured in terms of the generated output.  But he also con-
 tended that in cases where this value cannot be isolated for the input in
 question, benefits must be measured by an alternative method.  If the
 producer must substitute another input, then the appropriate estimate
 is the additional cost of doing so, also called "the opportunity cost of
 not being able to use the original input".

       Step 5 of Figure 2 translates the consumer surplus estimates
 (Figure 4) into a benefit curve, as shown in Figure  5.  There are
 numerous sources of uncertainty in these estimates, which account
 for the wide confidence bands.. around expected values.   For example,
 only a subset of the entire population is sampled in  deriving demand
 curves.  Biases in willingness -to -pay surveys are another source of
 error.  If the respondent believes that his answer will affect prices,
 he may purposely give a lower estimate. Or perhaps he is unsure of
 the value and thus gives different answers, depending on the time at
 which he is interviewed.

       It must be noted that benefit losses for product ctj represent
 only one  impact of consumer demand.  If there is a close substitute for
 this item, then its benefit losses will be partially negated by increased
 consumption and hence greater benefits for the alternate product or
 service.   To account for net benefit changes thus requires  the identifi-
 cation of all significant impacts, whether they are direct or indirect,
 competing or complementary,  short-term or (discounted) long-term.
 Added together, the individual  product and service benefits provide an
 estimate  of total social impacts.

      An  alternate method of estimating net benefits is to derive a
 willingness -to-pay curve  (Step 6) representing all impact simulta-
 neously.  By means of survey techniques, individuals are asked to
 estimate  the amount that would represent sufficient  compensation
 (excluding risks) for reducing current use of toxic substances.  Their
answers are then plotted against various toxicity control levels,  and
a benefit  curve w  is then  fitted through these sample observations.
                                 102

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       uo
       U-  (/>
       UJ  J-
       CO  f—
          o
       O
                                        Mean curve
                                        Confidence
                                         interval
                       INCREASING CONTROLS   -^~

                     (e.g.,  percent waste removal)
FIGURE 5.  FORMULATION OF PRODUCT OR SERVICE

            BENEFIT CURVE
                           103

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       Theoretically,  this curve should be equivalent to the net sum of
 all single product and service benefit curves derived in Step 5.  But
 this assumes that each individual is perfectly knowledgeable about the
 totality of benefits.  In practice, willingness-to-pay values are more
 likely to reflect a narrow, self- rather than society-oriented perspec-
 tive.   Biases in these values can thus be anticipated.  For instance,
 an individual will be  conservative if he fears that his answer might
 affect his tax base, while an overestimate is probable if he suspects
 that other members of society will be responsible  for payment.
                           RISK ANALYSIS
       Risks to human health and ecological systems constitute the
 second component of the conceptual framework. As toxic substances
 are removed from the environment or the food chain,  risks should
 decline correspondingly.  Social benefits from such action include an
 improvement in the health, safety,  and general welfare of the exposed
 population.

       The assessment of these impacts is described in Figure 6.
 Step 1 enumerates specific categories of either known or suspected
 risks.  If control levels (Step 2) refer to emission loads, they must be
 transformed into ambient concentrations of toxic substances to which
 the population at risk is- exposed.  Step 3 shows a typical model,
 whereby effluent loads are translated into ambient conditions by a
 waste diffusion process.  Other examples may be more complicated
 to predict, such as the accumulation of mercury derivatives in fish.

      Risk levels are then related to environmental quality according
 to Step 4.   This step is very crucial to the analysis, as it involves the
 assessment of risks, either probabilistic or deterministic,  over a
 range of quality (or control) levels.  Three types of risk are differ-
 entiated.   Some risks can be monetized,  e.g., medical costs and lost
 wages from illness.  Other can be  also quantified,  such as pollution
 tolerance levels of fish species, but their translation  into economic
 values is  questionable.  Either the item at risk has no price in the
marketplace, e.g., seagulls, or else it indirectly  supports commer-
 cial products but is not demanded in itself, e.g., phytoplankton in the
food chain culminating with commercial fish.  Still other risks cur-
rently defy any numerical or physical quantification, but are described
in qualitative fashion.  The preservation of environmental intangibles
such as aesthetics falls within this  domain.

                                 104

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      HEALTH AND ECOLOGY

          RISK ANALYSIS
           RISK PORTFOLIO


            ft - /J-
           COHTROL LEVELS

            l» ~ l»^ * l»« *  • • •


           ENVIRONMENTAL QUALITY
              AIR
   RISK VS. CONTROL

Economic     Non^ej
       P
       f     C            C
            RISK AVOIDANCE IMPACT
                              ic   Qualitative
            MONETARY WELFARE CURVE
           W
            WILLINGNESS-TO-PAY
              TO AVOID ALL RISKS
FIGURE 6.  SEQUENTIAL STAGES OF RISK ANALYSIS
                       105

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       Because risks are probabilistic and must usually be assessed
 without adequate data,  their mean values serve limited objectives.
 Instead, a stochastic interpretation of each risk level is more relevant.
 According to Figure 7,  this interval is bounded along the lower bofder
 but not along the upper one.  This distinction occurs for at least two
 reasons.   First,  in addition to typically mild cases of exposures,
 there maybe isolated reports of serious episodes,  e.g., human
 fatalities, caused by extended exposure to toxic  substances.  These ob-
 servations could fall far above the typical or mean risk curve.   Second,
 but more importantly,  there are unknown or as yet undiscovered risks
 whose recognition would either shift the mean curve upward or extend
 the confidence range far above the mean.  Because early warning
 systems must weigh such uncertainties, the confidence band should
 reflect the likelihood of future problems.  Thus,  unlike the balanced
 Gaussian distribution underlying most confidence measures, this band
 would be  skewed toward high risk values.   Note  that this function ranges
 over the original control level, which is derived from ambient quality
 according to the diffusion model in Step 3.

       The next step results in the transformation of risk avoidance into
 an expected economic returnT As  the risk of human accidents, sick-
 ness, or  fatalities decline, savings can be  anticipated in terms of lower
 medical costs, higher  wages from reduced absenteeism at work, etc.
 An expected  value of these  savings is depicted by the upward sloping
 curve.

       Finally, to circumvent the task of developing individual risk
 curves, willingness -to- pay surveys can be conducted to derive an
 aggregate welfare index. Analogous to that derived in the cost-benefit
 analysis,  the function cor (Step 7) depicts total economic gains of reduc-
 ing all risks  simultaneously, as controls on toxic substances become
 more stringent.

      In Figure  8, a typical welfare function is derived from increasing
 risk avoidance levels.  An S- shaped form is illustrated, with a hori-
 zontal asymptote defining maximal expected welfare.  This limit is
 necessary since each individual, with a finite income,  can afford only
 a limited insurance  premium to protect his health from unknown
 events.  The  S -shape has been empirically justified in a survey(^) of
 the amount, to, that  people are willing to pay to reduce their probabil-
 ity, p, of heart attacks  and premature death.  Mathematically, this
 function is written as,
                           co = e
where a and b are regression coefficients.  Typical confidence bands

                                 106

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    2
 ^  
-------
    Q 10
    UJ t—

    5 o
    _l T3

    ^ -

    ^
    to
                            Mean  curve


                            Confidence
                             interval
             RISK AVOIDANCE BY INCREASING CONTROLS

                (e.g.> higher survival  rate)
FIGURE  8.  ESTIMATION OF RISK-REDUCTION-WELFARE

            IMPACTS AT VARIOUS CONTROL LEVELS
                            108

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for this regression show the variation of people's perception of wel-
fare.  The distribution of family incomes influences this variation,
with wealthier respondents generally willing (and able) to contribute
more dollars.
      In addition to purely monetary values, there has recently been
concern about the  "nonpecuniary demand for safety". (3)  Irrespective
of monetary welfare impacts, this consideration could lead a con-
sumer to reject a  toxic substance -bearing product for a number of
personal reasons, including the following:  "...his talent and ability
to manage the operation of the product in question, his past experience
and success of similar undertakings,  and his natural propensity or
aversion for assuming  risks".  To compensate for this nonpecuniary
impact, the welfare curve is multiplied over its entire risk avoidance
range by a factor  exceeding unity.  Although this factor has been
described in theory, it has never been measured empirically, and
therefore remains subject to debate.
                       DECISION ANALYSIS
      After risks and cost-benefit impacts are evaluated, the decision-
maker can compare them for the purpose of setting optimal control
levels.  The objective is to set standards so as to maximize social
welfare, mathematically stated as the present discounted value of all
product and service benefits plus total risk avoidance gains.  Figure 9
depicts  four alternate approaches to optimization.  The selection of
an approach depends not only on the extent of information but on the
extent of monetary data.  The economic analysis, which relies  com-
pletely on dollar values, can proceed as a complete or partial assess-
ment.  The former relates total willingness-to-pay to changing levels
of toxic substance use. By superimposing the benefit and risk avoid-
ance functions,  w^ and o>r, respectively,  a social welfare curve is
derived as their sum.   Figure 10  illustrates the  manner in which the
best decision is identified.  From differential calculus, the social
optimum C^ is that point at which the derivative of the social welfare
curve vanishes.  (In cases where there are several local optima, the
decision-maker must choose the best solution.)

      The optimal solution is not so obvious as this simplified graph
indicates.   Willingness-to-pay curves for each benefit or risk (see
Figures 5 and 8) reveal that uncertainties play a  fundamental role  in
the analysis.  Consequently, the social welfare function becomes a

                                 109

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               OPTIMAL CONTROL  LEVEL DECISION-MAKING

     ECONOMIC                             ENVIRONMENTAL
       TOTAL ANALYSIS

     SUPERIMPOSE WILLINGNESS-
       TO-PAY CURVES
  £*^j
  D
        *    — -
         j •• •••••••*
              *••
            (E CURVES
                                 Aspi ration  level
  Budgetary constraint
  Technologic bound
FIGURE 9.  SEQUENTIAL STAGES OF OPTIMAL DECISION-MAKING STRATEGIES

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                        Social optimum C*
•8
                                                Mean curves

                                               Total welfare
                                               Risk-related
                                                 welfare


                                               Product
r

; ^ benefits
                       INCREASING CONTROLS   -^

                     (e.g.,  percent waste removal)
FIGURE  10.  SELECTION OF OPTIMAL CONTROL LEVEL IN
             RISK-BENEFIT ANALYSIS OF TOXIC SUBSTANCES
                              111

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 confidence band surrounding the mean curve.  The optimum is trans-
 lated into an interval of likely values with a derived probability dis-
 tribution, rather than a single value.  The decision-maker is  most
 likely to select themean value or a higher one,  if he is risk
 averse. ^13^

       To be meaningful, willingness-to-pay curves  should reflect the
 totality of benefit impacts.  However, no individual has a clear per-
 ception and understanding of all market and economic factors. More-
 over, there are inequity issues underlying one's  ability to pay.
 Family income levels will affect the magnitude of his response.  In at
 least one empirical study(^), willingness-to-pay was found to increase
 significantly with rising incomes.  At very high incomes (exceeding
 $50, 000) this trend tapers off and even dips  slightly.  Because of such
 distributional questions,  willingness-to-pay values  are not widely
 accepted in measuring economic impacts.

       Another approach based solely on monetary trade-offs is a par-
 tial assessment.  Several important benefit and risk avoidance
 functions are summed together to derive a social welfare function,
 after which the optimal control point (or interval) is determined.  Pro-
 vided that the economically most significant curves are chosen,  this
 partial approach should provide a reasonable approximation to the
 actual (total impact) solution.

       The above optimization strategies rely on monetary values.
 Obviously, there  are nonquantifiable aspects of the  environment as
 well.  The remaining strategies in Figure 9 are called "comprehen-
 sive" since they include noneconomic and economic data. In the com-
 plete analysis, all risk and benefit portfolios are enumerated (Step 1).
 To permit comparability of these values for policy-making purposes,
 all risk-benefit impacts must be determined over the same range of
 control levels.

       This one-to-one correspondence makes it possible to compare
 marginal impacts by sight,  and thus to quickly identify .those control
 levels likely to yield the greatest overall changes in risks and bene-
 fits.   The next three steps describe methods of selecting the best
 policy.  First,  a weighting scheme can be applied, such that magni-
 tudes of risks  and benefits are substituted into a "value function".
 This function can be exponential (as shown) or some other form,
whose value V rises as individual benefits increase  or risks decline.
Values are thus calculated over all control options,  and a maximal
level C. is found (Step 3).
       v

                                  112

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      Although weighting functions have been used in actual studies
[e.g., see Reference (14)], they lack general popularity.  Since
relative weights must be assigned, such functions explicitly trade off
monetary and nonmonetary impacts.   Of course, any decision-maker
is ultimately faced with this problem in designing policy; but to ex-
plicitly interrelate such impacts raises objections among ecologists,
many of whom claim that environmental quality cannot be described
in dollar terms.  Another  objection is that all  dependent variables
in the weighting fuction must assume numerical values, thus conflicting
with the meaning of nonquantitative risks.

      The simplest, and perhaps most popular, solution is to promote
"zero tolerance" of toxic elements.  That is, their use is completely
banned, in an effort to minimize health risks.   From a social welfare
point of view, this  approach is probably inefficient since it fails to
consider the benefits side.

      Of greater appear to environmentalists and economists alike is
a quasi-optimization approach called "marginal dominance".  The
decision-maker inspects risks and benefit curves individually, and
identifies those control levels at which marginal (changing) impacts
are extreme.  From previous remarks on willingness^-to-pay, these
marginal conditions may indicate the optimal solution.  But when
there is a large number of such impacts,  numerous control levels will
be identified.  Consequently, the problem then reduces to choosing
one optimum.  This choice depends on the implicit ranking of marginal
risks and benefits by the decision maker.  Thus, a value system must
still be applied, but at least it is not so obvious as to be repugnant to
many environmentalists.
                           CONCLUSION
      Policies on toxic substance control should not be derived from
subjective opinion.  If welfare of society is to be optimally enhanced,
a quantitative analysis  of benefits and risks is the most promising
approach. Recently, in fact, scientists have strongly advocated the
development of methods to assess competing impacts of product bene-
fits versus risks from  exposure to toxic elements.

      An operational framework is presented here for the purpose of
assessing welfare impacts of product or service benefits, health or
ecological risks, and then utilizing them in a decision-making analy-
sis.  There are several approaches to selecting the optimal control
                                113

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 level,  each appealing to a distinct audience and having specific ad-
 vantages.  Economic approaches  are simplistic in that they assume
 only monetary values.   Willingness-to-pay surveys provide a quick
 method of assessing the total value  of risks and benefits,  but their
 plausibility is frequently questioned.  Individual risks and benefits can
 be listed in a partial assessment, but the adequacy of this list may be
 difficult to ascertain.  Moreover, a large number of these categories
 may be necessary to cover a substantial portion of total effects.

       To the noneconomist,  complete dependence on monetary values
 is frequently unacceptable.  There are intangible or noneconomic
 aspects of the environment that should also be assessed.  To comply
 with their value system, a more comprehensive approach is developed.
 Here,  as with the pure economics approach,  the amount of risk-benefit
 data available determines whether a total or partial assessment is
 appropriate.  The latter is more  likely  in view of the limited time
 horizon over which controls on toxic substances  must be established.

       Because risks and benefits  are not necessarily translated into
 the same units,  e.g.,  dollars, the optimization procedure is not
 straightforward. A weighting function can be derived by assigning
 relative values to impacts at various control  levels, but this technique
 implies a direct comparison of monetary and nonmonetary impacts.
 An alternative method is to apply marginal dominance, whereby the
 greatest changes in specific risks and benefits are identified as con-
 trols become more stringent.  These changes will indicate the  most
 likely policies for welfare optimization.

      On the risk side,  there are  several unresolved problems of
 assessment. One involves the role  of uncertainty of the data base.
 A CRB analysis  based on currently available information  is likely to
 underestimate total impacts. As  more  knowledge about potential
 risks is discovered, the public seems more willing to pay to avoid
 these risks.  An example is  asbestos, which was of no concern fifty
 years ago but is now under intensive investigation because of recent
 findings on illnesses of asbestos plant workers. U5)

      Another problem concerns the protection of any natural eco-
 system or even a single  species.  While species fatality curves must
 be known,  risks  also pertain to changes  in metabolic rates, reproduc-
 tion rates, and modifications of the  food chain.   Complex  linkages and
 survival dependencies within an ecosystem make this analysis par-
 ticularly challenging.  Moreover the accumulation and synergistic
 effects  of toxic elements pose still another problem.  To  segregate
the effects with respect to each element may be impossible.
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      The complexity of risk-benefit analys.es is accented by the need
to evaluate risks and benefits over the same range of control levels.
This requires the translation of ambient exposure control levels (for
risks) into control standards on emissions or product content.  Pro-
vided that controls pertain uniformly to one industry or product, the
analysis presented here is applicable.  But if more than one generating
source of toxic substances is involved, the control variable is multi-
dimensional rather than single-valued (see Figure 3).  In this case,
the control parameter C is equivalent to a vector.

      As shown here, the operational framework for a CRB analysis
consists of numerous steps.   In theory,  however,  the procedure can
be explained more simply. (3)  But the gap between conceptual models
and their empirical application is surprisingly wide.  The CRB analysis
may be simplified to some extent by minimizing costs of controlling
toxic substances, subject to  the avoidance of certain risks.   But this
objective neglects the  (often  high) value of products containing or gen-
erating toxic elements.  Instead, this  study assumes that the control
costs are eventually paid by  the consumer in the form of higher
prices, and hence that product benefit changes reflect these costs.
                      ACKNOWLEDGMENTS
      The authors extend their appreciation to J.  Hibbs, E. Royce,
and F. Abel of the Environmental Protection Agency for their helpful
comments and criticisms.  Thanks are also due to various researchers
at Battelle Memorial Institute, the National Institute of Environmental
Health Sciences, and the National Science Foundation, who cosponsored
the seminar at which this paper was presented.

      The opinions expressed in this study are those of the authors
and do not represent the official views of the Environmental Protection
Agency.
                          REFERENCES
      R. C. Lind, "The Analysis of Benefit-Risk Relationships:
      Unresolved Issues and Areas for Future Research", Perspec-
      tives on Benefit-Risk Decision Making, Colloquium Proceedings,
      The National Academy of Engineering, Washington, B.C. (1971).

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  2.    President'$ Science Advisory Committee,  Chemicals & Health,
       Report of the Panel of Chemicals and Health, Science and Tech-
       nology Policy Office,  National Science Foundation,  Washington,
       B.C.  (1973).

  3.    C.  D. Muehlhause,  Risk-Benefit Analysis in Decision-Making,
       Department of the Environment, Ottawa (1972).

  4.    J.  Griffith, "The Role of Social Scientists in River Basin Plan-
       ning:  A Critique", Journal of Environmental Systems, 3_, 131-
       152 (1973).

  5.    D.  J.  Etzold,   Benefit-Cost Analysis: An Integral Part  of
       Environmental Decisioning, Journal of Environmental Systems,
       3_,  253-256 (1973).

  6.    B.  Ostle, Statistics in Research, The Iowa State University
       Press, Ames, Iowa (1963).

  7.    S. Eilon and T. R. Fowkes, "Sampling Procedures for Risk
       Simulation", Operational Research Quarterly, 24, 241-252
       (1973).

  8.    Battelle Memorial  Institute (Columbus Laboratories), "Effects
       of Chemicals on Aquatic Life",  Vol.  3, in Water Quality Criteria
       Data BookT U.  S. Environmental Protection Agency, Washington,
       D.C. (1971).

  9.   M.  Dragomiresou, "An Algorithm for the Minimum-Risk Prob-
      lem of Stochastic Programming", Operations Research,  20,
       154-164 (1972).

10.   G.  Provenzano, "Risk-Benefit Analysis and the Economics  of
      Heavy Metals  Control",  Proceedings of the Conference on
      Heavy Metals in the Aquatic Environment, Vanderbilt University,
      Nashville, Tenn. (1973).

11.   J.  P. Acton, Evaluating Public  Programs to Save Lives;  The
      Case of Heart Attacks, The Rand Corporation, Santa Monica,
      Calif.  (1973).

12.   M.  J. Roberts,  S.  Oster,  and M. Hanemann, Study of the
      Measurement and Distribution of the  Costs and Benefits of
      Water Pollution Control, U. S.  Environmental Protection
      Agency, Washington,  D.C. (1974).

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13.   H.  Raiffa, Decision Analysis;  Introductory Lectures on Making
     Choices Under Uncertainty,  Harvard University,  Cambridge,
     Mass. (1968).

14.   R.  Stone and H. Friedland, "Estuarine Clean Water Cost-
     Benefit Studies", Proceedings  of the Fifth International Water
     Pollution Research Conference, San Francisco, Calif.  (1970).

15.   J.  Churg, E.  C. Hammond,  A. M.  Langer,  W. J. Nicholson,
     I. J. Selikoff, and Y. Suzuki,  Biological Effects of Asbestos,
     Environmental Sciences Laboratory, Mount Sinai School of
     Medicine and the City University of New York, N.  Y.  (1973).
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        THE PROBLEMS WITH EARLY-WARNING SYSTEMS
                     FOR TOXIC MATERIALS*

                          W. Fulkerson**
                  Oak Ridge National Laboratory***
                       Oak Ridge, Tennessee
                            ABSTRACT
       The information required for the estimation of health and en-
 vironmental impacts resulting  from discharges and/or use of toxic
 materials is reviewed. An ideal system is proposed (the straw man
 approach) in which hazard is equated to the product of some function
 giving the exposure rate to man and other biota, and a function ex-
 pressing the toxicity of a material.  The information required to
 implement such a  system including data on the flow of the material in
 society  (manufacturing use, and disposal patterns), persistency and
 low level chronic exposure effects are enumerated.  The difficulties
 in obtaining the information are discussed including cost and statutory
 limitations. Some alternatives to the ideal system are proposed.
  *Work supported by NSF RANN Environmental Aspects of Trace
Contaminants Program under NSF Interagency Agreement No. AG 389
with the AEC.

 **Principal Investigator, NSF-RANN sponsored Ecology and Analysis
of Trace Contaminants Program.

**#Operated by Union Carbide Corporation for the U.  S.  Atomic Energy
Commission under Contract No. W-7405-eng-26.

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                  1974 - A YEAR OF TRANSITION

                        Glenn L. Schweitzer
                     Office of Toxic Substances
                 Environmental Protection Agency-
                        Washington, D. C.
                          INTRODUCTION
      During the past several weeks,  talk in Washington has centered
in large measure on the achievements during 1973 - or perhaps we
should say the events during  1973.  All agree that it was a tumultuous
year with our domestic and environmental concerns largely overshad-
owed by unprecedented political events at home and abroad.

      1973 was to be the  year when the momentum of the environmental
movement began to take us around the corner in cleaning up the air and
the water. Our arsenal of regulatory tools for insuring product safety
and sound disposal practices was to be expanded.  And  a degree of
harmonization was to be  achieved between economic progress and
environmental controls.

      But this was not the case.  Energy concerns threatened to reverse
past environmental gains.  Congressional attention was diverted from
the details of environmental legislation.  And perhaps most unfortunately
the influx of top young talent  into the environmental picture seemed to
slacken.

      However, environmental milestones were far from lacking during
1973.  For example,  in the area  of toxic substances:

      —  The chemical industry is still reverberating from the
         Department of Labor's stringent interim standards for
         handling 14 carcinogens, including several of  consid-
         erable commercial importance.

      —  FDA banned the use of DES as a feed additive  over
         the  strong objections of the cattle ranchers.

      —  EPA1 s promulgation of final air emission standards
       . and proposed water  effluent  standards for toxic
         pollutants are causing major adjustments in manu-
         facturing practices at many  facilities.

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          Promulgation of final leaded gasoline regulations
          culminated several years of effort to address the
          severity of the problem of lead inhalation and
          human health.

          Discovery of high levels of asbestos fibers in
          the Duluth water supply has catalyzed a large
          array of technical  talent to address what could
          turn out to be either  a sleeping giant or a false
          alarm of major dimensions.

          The tussock moth outbreak on the West Coast
          highlighted the environmental and economic
          "disbenefits" resulting from the ban on DDT.

          Finally, the National Center for Toxicological
          Research in Pine Bluff, Arkansas,  became a
          viable operation that is  making its mark in ths
          regulatory world.
                        THE ISSUES FOR 1974
       While the number and diversity of issues in the environmental
 field continue to grow, many of the most important questions to be
 addressed in the immediate future in my specific area of concern are
 the well-known "old chestnuts".  Traditionally, we tend either to take
 these issues for granted or skirt them because of their difficulty.  In
 either case we then focus on other questions which are also important
 but which could be irrelevant if our fundamental  approach is not sound.
 Let me cite four of the "old chestnuts" which are certainly near the top
 of our list.
    Toxicological Testing and Standard Setting;  Can We Do Better?
      Emblazoned in laws and in the Federal Register are standardized
approaches to a very complicated  science — standardized approaches
that date back many years and, having gained a type of legal status,
seem almost immune from scrutiny and revision.  As an engineer I
should feel comfortable in surrounding the biological sciences with
accepted quantifiable approaches and easily defined safety factors, but

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I am not.  In my view, a thorough review — initially by the scientific
community itself - of the currently accepted approaches to generation
and interpretation of test data is needed.

      In this regard, EPA recently proposed a numerical standard for
the carcinogen benzidine based on-the concept that in determining the
standards, the level of risk which is  acceptable must be  considered in
the light of the benefits derived from the chemical. Derivation of this
level of risk requires types of test data not ordinarily  generated  by
toxicologists, thus suggesting a significantly different  approach to test-
ing carcinogens, and perhaps other chemicals as well.

      In large measure the issue revolves around how  the scientist
packages the toxicological data for the decision-maker.  If the scientist
structures the experiment and packages the data to derive simply a
"safe" level for chemical exposure, then the decision-maker has only
one option,  and all other factors become irrelevant.   The scientist has
in fact assumed responsibility for  consideration of the total impact of
a regulation on society.  On the other hand,  if the scientist  presents
several options, with explanations of the health and environmental
implications of each, then the decision-maker can indeed take into
account a wide range of social and economic implications at different
levels of chemical exposure.
              Risk/Benefit Aspects of Toxic Substances;
                   The Theorist or the Pragmatist?
      Even though toxic substances are by definition dangerous to health
or the environment, there seems to be general agreement that in devel-
oping control strategies some balancing of risks and benefits is in order,
as reflected  in the EPA action on benzidine.  In the past, elaborate
cost/benefit  models have frequently had little operational relevance.
At the same  time we must do better than those past efforts that tend to
focus only on the short-term, direct costs of environmental controls
which are  susceptible  to quantification.

      Perhaps the most formidable task is estimating the incremental
gains to society — or the reduction of risks to society — by decreasing
the level of a toxic substance entering the environment.  Human poison-
ing, fish kills, and flora destruction can of course frequently be related
to specific discharges.  But these near-term,  easily isolated incidents
which can  be used to correlate discharge levels with economic and social
impact are the exception rather  than the rule.  A  second problem is to


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 estimate how much the level of exposure will be reduced by a specific
 control measure.  Even if good monitoring data exist concerning cur-
 rent exposure levels,  to project ahead the impact of a proposed mea-
 sure is difficult indeed. And finally,  of course, is the cost of the
 control measure,  which usually involves much more than simply pur-
 chasing control devices.  For example,  in response to the  Department
 of Labor restrictions on carcinogens, one company was forced to
 replace the carcinogen with another intermediate chemical which
 turned out to be far more cost/effective for the particular process.
 Had it not been for the  regulation,  and subsequent R and D  effort by
 the company, this cost-saving innovation would still be  lying dormant.

       What should be the approach to risk/benefit analyses?  With
 regard to the known problem substances, I suspect that in the  short
 run we will do little better than weighted checklists to be used as
 general guidelines for at least surfacing some of the concerns before
 decision-making time.   Case studies of specific past decisions should
 be particularly helpful in this regard.  In the longer term,  I don't know
 if a more objective approach can be developed that is broadly applicable
 to balancing  risks and benefits.

       However,  a far more difficult problem faces us in answering the
 question:  "How much is society ready to pay to search out other prob-
 lem substances  before they emerge as problems on the  immediate
 horizon? "  Or "What should be the cost of early warning? "
          A Generalized Approach to Control Strategies for
             Multimedia Pollutants;  Reality or Fantasy?
      A number of the most troublesome toxic pollutants enter the envi-
 ronment from many sources, follow multiple routes through the environ-
 ment, and come to  rest in a  variety of places.  Studies have illustrated
 many of the complexities of movement and fate of pollutants.  Such studies
 were particularly helpful in addressing the lead issue, as one example.

      Can there be  a generalized approach to control strategies for a
 large number of toxic pollutants with multimedia characteristics?
 Perhaps the behavioral and use idiosyncrasies of different chemicals
 require completely different approaches to the formulation of control
 strategies.  Two of our most relevant experiences to  date in  developing
 control strategies have been the attempts to  control selected  toxic
pollutants under different sections of the axr and water legislation.

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These single media approaches to control strategies clearly underscore
the difficulty of generalized approaches.

      Obviously,  there should be some correlation between the controls
that are selected to^mitigate the problem associated with a specific
chemical and the portion of the problem that these controls actually
address.  Similarly,  in considering the total allowable body burden for
a chemical, there should be some consistency in allocating the total
among individual control measures.  But can we be much more specific
in generalizing approaches,  say, to three of the most widely discussed
toxic chemicals,  namely, cadmium,  mercury,  and PCB's?  It is diffi-
cult to identify the common aspects of cadmium-coated screws, mer-
cury-containing dental amalgam, and polychlorinated biphenyls used
in transformers, which would fit into general control strategies.  Once
again, at least as an  interim step,  I would argue for case studies as
providing a background of experience in addressing future approaches
to multimedia pollutants.
       An Operational Early-Warning System: Is It Practical?
      The need to identify and remedy problems before they take their
environmental or health toll seems axiomatic.  But can this be done on
more than a token basis?  Clearly, this question goes to the  heart of
this Conference.

      Several approaches to problem identification seem reasonably
clear:

      —  Gatherings of experts, such as this meeting, and also
         organized on an industry-by-industry basis.

      —  Review of past  incidents to identify early-warning
         indicators.

      —  Current awareness systems to identify reported and
         unreported incidents involving toxic substances.

      —  Forecasts of market and economic trends and their
         impact on the future mix of products and  activities
         of the cheiuical industry.

Many of you have promoted activities in these areas for some time,
and we will be joining you in all of these areas in the months ahead.

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      What is most needed now?  Better use of existing early warning
 systems?   Bigger and better systems?  More systematic orchestra-
 tion of the multiple systems?  I hope you will clarify these questions.

      However, there undoubtedly will remain a major gap between
 problem identification and preventive action.  Bridging this gap is
 particularly difficult for a bureaucracy that is basically  reactive to
 immediate problems - and reactive in a very short-term mode.   Thus,
 persuasive argumentation  supporting the action recommended by the
 early warning network is essential.

      Even assuming that false alarms  have been separated from
 potentially serious problems, it will be difficult indeed to impose res-
 trictive measures before the fact largely on the basis of unsubstan-
 tiated data.  In my view, unless there is extensive cooperation on the
 part of industry in heeding the early warning signals - cooperation
 reflected in a great deal of restraint on a voluntary basis — the products
 of the best conceived early-warning systems are not likely to make a
 major impact on more than a small handful of a much larger array of
 potential problem substances.
          THE CHEMICAL INDUSTRY AND POLICY ISSUES
      The industrial representation at this Conference is encouraging.
Indeed, in recent months a number of companies have shown consid-
erable leadership in enhancing product safety,  in improving the envi-
ronmental compatibility of manufacturing processes, and in expanding
R and D efforts to further clarify the  risks of chemical activities.

      For our present purposes we are interested principally in those
manufacturers and processors who introduce chemical changes into
their products.   The following characteristics of this sector of
industry — excluding the food, drug, cosmetics, and pesticides seg-
ments — seem particularly relevant:

      —  The annual value added to products is  in the range of
         $110 billion, about double the level ten years ago.

      —  About 20, 000 chemical products are in commerce
         with an additional 500 chemicals being added
         annually.
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      —  More than 80 percent of sales is concentrated in
         several dozen companies but there are hundreds
         of additional small manufacturers.

      —  A large percentage of net income — ranging from
         20 to 50 percent — is usually reinvested in R and
         D.

      A number of policy considerations of particular concern to indus-
try permeate a regulatory approach to this sector of industry, from
early warning to restrictions.  Some  of these concerns are:

      —  The disincentives to  R and D inherent in some
         types of regulatory actions could blunt the
         technological thrust of the industry.

      —  The configuration of the industry (e.g., large
         and small manufacturers, specialized and
         diversified firms) could be affected by reg-
         ulatory actions which are more painful to
         certain types of companies.

      —  Regulatory actions undertaken unilaterally
         by the United States  could affect the
         competitiveness of our products at home
         and abroad.

      This does not mean that-environmental actions should not affect
economic interests, for environmental control is not free.  However,
we should recognize that individual actions — and also aggregated
actions — can have many secondary and tertiary effects which may be
far more significant than the  more obvious primary effects.  The key
question of course is whether the environmental gains from regulatory
actions are commensurate with any adverse economic and social
impact - a question that is easy to ask but difficult to answer.   In any
event, we must treat early-warning signals in a responsible fashion
lest the potentially affected parties seek to bury the signals out of
concern that they will not be handled responsibly.
                                  125

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                          LOOKING AHEAD
       Clearly Washington's preoccupation with non-environmental
 issues will continue to detract from the high level attention devoted to
 toxic  substances in the months ahead, particularly on Capitol Hill.
 For some of the newer programs this may be a fortuitous development
 which will allow us to do a better job in planning long range activities,
 even though all of us would like to move  ahead with operational activities.

       During 1974 we should continue to press forward vigorously on all
 fronts,  recognizing that regulatory actions will be more difficult amidst
 the general  skepticism as to the importance  of environmental control
 being expounded in some quarters.  There is no reason,  however, why
 we should not make great strides in many of the essential supporting
 activities.  There is general agreement on the importance of increased
 efforts to clarify the need for, character of,  and impact resulting from
 steps to prevent and mitigate environmental problems.  Thus,  I would
 characterize 1974 as a year of transition — a year between a  period  of
 talk and rhetoric about the need -for  new regulatory approaches to reduce
 risks associated with toxic substances and a period of accelerated
 action to address these  risks.   1974 should be a year of coalescing ideas
 and energies, a year of engaging all the  affected parties,  and a year of
 setting the stage for a sensible long-term effort in dealing with multi-
 media pollutants.

       In future years, more chemicals will be in commerce,  the prop-
 erties of many chemicals will be better understood,  and consequently
 the list  of chemicals considered to be hazardous to man and the envi-
 ronment will undoubtedly be much longer. Also, improved research
 and analytical capabilities  will show that the effects of these chemicals —
 acting individually and synergistically — are much farther reaching than
 currently suspected effects.

       Even though in a few years the emission stacks and  effluent pipes
 will be largely plugged, and hopefully sensible land  disposal of hazard-
 ous wastes will be required, more people will be exposed to more
 chemicals in more  situations — exposure from contaminants,  non-point
 sources, direct product contact, and generally unattributable buildup
 of chemicals in the environment.  I am confident that society can de-
velop the necessary precautionary measures that will limit exposure to
 chemicals when necessary, but not unnecessarily curtail commercial
activitie s.
                                 126

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      There is, of course, a danger that society will not act responsibly
in anticipating and remedying toxic substance problems through its
governmental and other institutions, with the inevitable outcome of
endless legal confrontations.  The entire approach to toxic substances
could become bogged down in the courts - which would be a tragedy
for us all.                                                          *

      Thus, the challenge to early warning is clear. It is a  challenge
that will

      —  Prioritize and focus the concerns of Government and
         of society on those chemical/biological interactions
         that require particular scrutiny in the months and
         years ahead;

      —  Provide the time needed for  sluggish governmental,
         industrial, and commercial mechanisms to take
         almost unprecedented anticipatory actions; and

      —  Instill a sense of public confidence that the products
         of chemistry — both new types of goods and substi-
         tute materials for rapidly dwindling natural mate-
         rials — can be made compatible with an increas-
         ingly fragile biosphere.
                                  127

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         REVIEW  OF HEALTH/ENVIRONMENTAL SYSTEMS
         WITH POTENTIAL EARLY WARNING APPLICATIONS

             Theodore James Thomas and James E. Flinn
                               Battelle
                        Columbus Laboratories
                           Columbus, Ohio
                             ABSTRACT
       This paper summarizes a study performed for EPA's Office of
 Toxic Substances on the state-of-the-art of systems, either existing
 or conceptual,  that can be used or adapted for use to select, assess,
 and prioritize chemicals for their health or environmental effects.
 It is found that, while numerous systems can be identified, none have
 been formulated with sufficient breadth to permit accomplishing all
 these functions in a comprehensive manner.

       Effective combinations of limited scope systems have been
 assembled by Federal agencies to achieve the chemical identification/
 assessment/prioritization functions needed for such public concerns
 as the work-place environment; human health (cancer,  child poison-
 ing, birth defects); air, water, and land contamination;  and consumer-
 product hazards.  Examination of the operational basis of a number of
 the individual systems within these combinations suggests that all are
 variations of a  relatively few number of approaches to chemical
 selection.  Three approaches for  a prioritization/evaluation system
 are condensed from this examination.
                           INTRODUCTION
      Our present systems for monitoring the hazards of newly intro-
duced toxic chemical substances are inadequate.  They may deal with
substances after their use in products is widespread.  Revelations
concerning an environmental or health hazard are often made haphaz-
ardly, accidentally,  or  simply too late.  Frequently, the indicators
are there but systematic exploration of the implications  of the initial
findings  is not accomplished.
                                  128

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      Public concern over DDT,  cyclamates, mercury,  and numerous
other chemical substances which have crept into the environment
through technological advancement has clearly indicated the need for
improved early detection,  assessment, warning, and corrective
measures with respect to the misapplication of intrinsically toxic
substances.  This identified need could be satisfied through the estab-
lishment of an early warning system for toxic chemicals.   Ideally,
an early warning system would provide hazard predictions  which are
(1) thorough or all-encompassing with respect to potential sources,
(2) discriminating through reference to indicators of potential hazards,
(3) adaptable to current usage, i. e., within the framework of existing
technology and societal systems, and (4) amenable to the establish-
ment of priorities for the identified substances.

      The Environmental Protection Agency, through its Office of
Toxic Substances (OTS), contracted with Battelle's Columbus Labora-
tories to identify and evaluate systems which could be adapted by
EPA's Office of Toxic Substances to identify, assess, and prioritize
chemicals or classes of chemicals with respect to environmental and
health hazards. A major premise of the study was that systems or
methodologies do exist which, if modified and/or redirected to the
selection and hazard evaluation of chemicals or classes of chemicals,
would provide a stepping stone toward satisfying the needs of an early
warning system.   Specific questions raised by OTS were these:

      (1)  How can a given system select both chemicals and
          classes of_chemicals that are hazardous to man
          and his environment?

      (2)  How can a given system preselect chemicals  not
          already in use,  before they become widely
          dispersed and more difficult to  control?

      (3)  How can a system select chemicals based on the
          potential hazard of their degradation products
          or their synergistic properties?

      (4)  How should the  system consider hazards to
          plants,  animals, and nonliving environment?
                                 129

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                              RESULTS
       In the performance of this study, a literature and state-of-the-
 art search was made to identify systems - either in use or only con-
 ceptual - in two general areas of societal activity:  health planning
 (including environmental,  occupational, and general health) and envi-
 ronmental management.  The term "system" was broadly defined to
 include not only formalized organizational structures, models, meth-
 odologies, but also less formal tools, methods, working groups, etc.,
 which have been conceived, formulated and applied to the identification,
 prediction,  assessment, or prioritization of chemical substances or
 effects.  A variety of activities comprised the total information gath-
 ering effort, including  manual and automated literature searches and
 personal contacts.
              Identified Systerns and Their Classification
       In this study a great many systems have been identified which
 singly or in combination provide some of the functions desired  in the
 selection of chemicals with respect to their hazards to man and the
 environment.  Nearly all of these do so within a limited domain of
 concern, i.e., the workplace, the air, water or land environment,
 an ecosystem,  or an aspect of human health (cancer, poisoning, aging,
 birth defects).  From the standpoint of the  mission an agency like
 EPA's Office of Toxic Substances, this diversity of systems repre-
 sents  an asset, one to be capitalized upon in seeking the identification
 and hazard evaluation of chemicals for which regulatory actions
 ought to be imposed.  Conversely, this same diversity complicates
 the problem of effectively gaining access to all the data necessary to
 provide a regulation which properly balances public  risk,  cost, and
 benefit.

      Table 1 lists a number of systems which were identified in the
 course of this study.  These are described  further in Battelie's final
 report to EPA. W

      It has been found useful to separate the identified systems into
two major categories depending upon whether their principal purpose
was to identify or evaluate environment or health stressors  either
prior to general exposure of the public and  environment (Category I)
or after widespread exposure or use occurs (Category II).   The first
category was referred to as input surveillance (and assessment) and


                                   130

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                           TABLE 1.  IDENTIFICATION/ASSESSMENT SYSTEMS
         System Identlfer
            Sponsor
ZA
Category
ZB    HA
ZZB
(1)  Carcinogen Screening

(2)  Animal (Rat) Toxlcity Test
(3)  Short-Term (Hamster) Cancer
       Test
(4)  Biological Materials
       Surveillance
(5)  Surveillance of Poisons
(6)  Radiological Product
       Surveillance
(7)  National Evaluation of X-Ray
       Trends
(8)  Biologies Licensing
(9)  Drug Surveillance

(10) Chemical Hazard Identification
(11) Poison Control Centers
(12) Epidemic Intelligence Service
International Agency for Research
  Against Cancer
Center for Disease Control
National Cancer Institute
Bureau of Biologies, Food and
  Drug Administration
National Clearinghouse for
  Poison Control, Food and
  Drug Administration
Bureau of Radiological Health,
  Food and Drug Administration
            Ditto
Department of Health, Education,
  and Welfare
Bureau of Drugs, Food and Drug
  Adminls tra t ion
National Cancer Institute
State Departments of Health
Center for Disease1' Control
X

X
      x

      X

      X

      X

      X
             X
             X
             X

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                                          TABLE 1.   IDENTIFICATION/ASSESSMENT SYSTEMS
                                                         (Continued)
N>
                       System Identifier
                                                   Sponsor
IA
Category
IB    IIA
IIB
(13) National Electronic Injury
       Surveillance System

(14) National Surveillance Network -
       National Occupational
       Health Survey

(15) Toxic Substance List

(16) Prioritizatlon of Workplace
       Chemicals

(17) Hazard Evaluation Program

(18) Walter Reed Disease Forecasting
       System

(19) Community Health Effects
       Surveillance Studies

(20) Cancer Surveillance,
       Epidemiology and End
       Results Reporting Program

(21) Subclinical Toxicity Survey

(22) Technicalt Intelligence, and
    ,   Project Information System

(23) OVERVIEW System

(24) National Emissions Data System
       (Air)
                                                     Consumer Product Safety
                                                       Commission

                                                     National Institute of Occupa-
                                                       tional Safety and Health


                                                                 Ditto
             X


             X


             X
                                                                    II

                                                                    II
                                                                U.S.  Army
                                                     Research Triangle Park, Environ-
                                                       mental Protection Agency
                                                     National Cancer Institute
                                                     Center for Disease Control

                                                              (Conceptual)
                                                                 Ditto

                                                     Environmental Protection Agency
      X

      X


      X
              X

              X


              X


              X



              X

              X



              X

-------
                                        TABLE 1.  IDENTIFICATION/ASSESSMENT SYSTEMS
                                                       (Continued)
CM
CM
                      System Identifier
                                                   Sponsor
             (26)  International Decade of Ocean
                    Exploration
             (27)  Marine Resources
(28) National Stream Quality
       Accounting Network
(29) international Biological
       Program
(30) SAROAO
(31) STORE!
(32) Environmental Monitoring
(33) National Fuels Surveillance
       Network
(34) Wiswesser Line Notation
(35) Environmental Information
       System Office
(36) OHM-TADS
(37) National Pesticides Monitoring
       Program
(38) Priorities for Synthetic
       Organic Chemicals
(39) Toxicology Information
       Program
National Science Foundation
National Oceanic and Atmospheric
  Adminls tration
U.S. Geological Survey
National Science Foundation
Environmental Protection Agency
            Ditto
Council on Environmental Quality

Environmental Protection Agency    X
                                   X

Oak Ridge National Laboratories
Environmental Protection Agency
tf
          Interagency
Syracuse University Research
  Corporation

National Library of Medicine
                                                                                             Category
                                         IB
IIA    IIB
             (25)  General Point Source File (Water)  Environmental Protection Agency
                                                                                                   X
                                                                                                   X
                                                                                                          X
                                                                                                          X
                                                                                                   X
                                                                                                   X
                                                                                            X
       X
       X

       X

       X

       X

-------
 the latter as output surveillance.  Each of these categories can be
 further subcategorized depending on whether the  system activity is
 primarily related to identifying the existence of a possible health or
 an environmental stressor.  In Table 1 the identified systems are
 listed along with a judgment regarding their appropriate categories
 formulated according to the following scheme:

       I.  Input Surveillance
 A.
 A.
      I      ^
New Stressor
Ide ntification

 II.  Output Surveillance
          —I	
                                                I
                                   B.  Hazard Assessment of
                                       Recognized Stressors
      I
New Stressor
Identification
                                   B.  Hazard Assessment of
                                       Recognized Stressors
       One large class of systems identified in this program is the
 information repositories or data banks, some automated for storage
 and retrieval,  others simply collections assembled in one location.
 Table 2 lists a number of these selected from an initial list of approx-
 imately 650 information centers in the United States. (2)  The list,
 not meant to be complete,  is  divided into groups with or without
 computerized access and further as primarily chemical, medical,  or
 general sources of information.  The listing  suggests that considerable
 amounts of information for chemical identification or assessment
 purposes are available.  The problem is to determine what is available,
 its form, and its accessibility for identification/assessment purpose.
 More extensive examination of these type systems was felt beyond  the
 scope of this study.
                 System Identification,  Prioritization,
                       and Evaluation Functions
      While  systems of Table 1 are primarily those used by govern-
mental agencies in the health and environmental areas, there are
probably as  many industrial and private systems that could be identi-
fied.  For example,  it became apparent during the study that  even a
public-interest group,  such as the Center for Science in the Public
Interest, can function as a system for alerting the public to the
                                 134

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 hazards of toxic substances.  The larger industrial chemical firms
 undoubtedly have internal systems for the identification and assess-
 ment of new chemical hazards.

      A sufficient number of system types has been identified in this
 program to provide convincing evidence that

      (1)  No system exists which in itself will accomplish
           all the selection and assessment functions for
           toxic chemicals implied in the questions posed
           by OTS.  A few provide some of these functions
           in limited areas,  such as carcinogenic,  work-
           place,  or environmental hazards.   A basis for
           adapting these including all functions (such as
           assessing synergistic effects) is not readily
           apparent.

      (2)  While many additional systems could be
           identified through continued search efforts,
           it is believed that these would turn out to
           provide essentially the same general func-
           tions as those reported in this study.  In
           general, these functions include surveil-
           lance,  surveying, monitoring, screening,
           reporting,  sampling,  testing, data compi-
           lation,  or manipulation, etc., for identi-
           fication, assessment, or prioritization
           purposes.

      These observations will become clearer upon further examination
of some underlying commonalities and differences between the various
system methodologies.
Commonalities and Differences
of Identified Systems
      In studying the identified systems, some underlying commonali-
ties of methodology were recognized.  For example, the scope of the
existing systems directed at chemicals is without exception more
specific than the perceived needs of OTS.  Existing system? have
their scope limited by:
                                  135

-------
       (1)  class of chemicals
       (2)  the source of chemicals
       (3)  the transport media leading to exposure, and/or
       (4)  the affected species.

 In addition,  existing systems focus implicitly upon acute  rather than
 chronic effects, due mainly to the orientation of published literature
 towards acute effects.  Thus, while the  systems identified might be
 recognized as partial solutions to OTS1 needs, the expansion of the
 scope of any existing system is obviously not easily accomplished.

       Another area of commonality lies  within the goals of existing
 systems.  Almost every system studied has as a basic goal the deter-
 mination of a potentially hazardous subset of chemicals or chemical
 classes from a larger list of candidates.  This process may be accom-
 plished in a single step,  or a hierarchy  of steps may be employed,
 with each step again consisting of the determination of a potentially
 more hazardous subset.

       Each step may be viewed as a process in which information is
 gathered for  the list of chemical candidates and combined in some
 manner to produce an assessment of the estimated hazard on a uni-
 variate scale.  The utilization of judgment to provide a true/false
 answer to the question of hazard is an example of the combination/
 assessment process.

       The original step of the hierarchy does not have a preceding
 step to provide a candidate list.  Many existing systems have devel-
 oped sensor networks to generate the chemicals on the original candi-
 date list.  One frequently employed sensor network for existing
 systems is the use of the  literature, i.e., either monitoring the raw
 literature or condensations of literature.  The NIOSH Toxic  Substances
 List^3), for example, relies  upon Chemical Abstracts as a source of
 chemical names and information.  Further information needed for
 the list is  obtained from the open literature.  Some systems studied,
 however, relied upon previously published candidate  lists, hence the
 first step had been previously accomplished for these systems.
 Another example of a sensor network for the generation of an original
 candidate list, typified by the approach used by the National  Pesticide
 Monitoring Program,  was the collected judgment of professionals,
queried and resolved by the Delphi technique.  This approach is fea-
 sible when the candidate list  is relatively small.

      Some "sensor" networks are monitoring networks in the real
environment.   The NIESS  system of the Consumer Product Safety

                                  136

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Commission,  for example, generates its candidate list for hazards
from hospital emergency room reports.  This approach is useful
when a direct, measurable cause-effect result can be observed after
the fact.

      After their sensor networks establish candidate lists of chemi-
cals, existing systems determine a potentially hazardous subset of
chemicals through a single or  repeated application of information
collection and decision making.  The large number of sources of
chemical information was referred to earlier (Table 2).

      After the information is  collected,  existing systems manipulate
the information to form a design basis by which prioritization/classi-
fication decisions can be  made.  A general framework has been
structured which expresses the design basis of most existing prior-
itization systems.  This general basic system for prioritization or
categorization accepts from the universe of knowledge a small subset
of information.  This information subset is then processed and
combined to produce categories or priorities.  Graphically,  the
process is as follows:
ITEMS TO BE
CATEGORIZED
OR PRIORITIZED
s^
r~
PRIORITIZATION
OR
CATEGORIZATION
SYSTEM

s
CATEGORIZED
OR
PRIORITIZED
ITEMS
To design or adapt a prioritization/categorization system,  it is neces-
sary to specify

      (1)  The subset of information to be used by the system
      (2)  The algorithm by which the subset of information
          will be manipulated and combined.
                                  137

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         TABLE Z.  CHEMICAL TOXICITY DATA SOURCES
A.   Sources with Automated Storage and Retrieval Facilities

        Chemical
        Sadtler Research Laboratories, Inc.
        American Chemical Society
        Columbia University RADICAL System
        Commission of the European Communities - ECDIS

        Medical

        University of Rochester
        North Carolina State University
        Midwest Research Laboratories
        National Library of Medicine
        Biological Abstracts
        General

        The John Crerar Library
       Argonne Code Center
        Battelle Memorial  Institute (Columbus and Northwest)
       Atomic Energy Commission  - Division of Technical Information
         Extension
       Nuclear Safety Information Center
       Pesticides Information Center

B.   Other Information Centers
       Chemicals

       Household Substances Data File, FDA
       The Soap  and Detergent Association
       American Petroleum Institute
       Industrial Hygiene Foundation of America, Inc.
       Tobacco Literature Service

       Medical

       National Center for Chronic Disease Control
       Army Munitions Command - Toxicological Information Center
       New York Academy of Medicine
       National Clearinghouse for Poison Control
       Pharmaceutical Information Service
       Pharmaco-Medical Documentation

       General

       International Association of Water Pollution Research
       National Academy of Science-Engineering
       World Life Research Institute
       Institute for  Scientific Information
                               138

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Examination of the existing systems suggests three approaches to the
design of a prioritization/categorization algorithm

      (1)  The "wise man" approach, a subjective design where
          the system framework is established on the basis of
          perceived needs and an assessment of available
          resources.  The National Pesticide Monitoring Pro-
          gram, and many contemporary systems appear to
          have been formulated this way.

      (2)  The "index" approach, a design based upon a
          specific ranking parameter formed algebra-
          ically and/or logically from other data.  This
          would be exemplified by a system for ranking
          hazardous waterborne substances by the volume
          of water necessary to dilute expected annual
          spillage to a safe or limiting concentration. *  '

      (3)  The "optimized" approach, designs wherein the
          parameters are selected for producing categories
          or priority ranking on the basis of assigned values
          and weightings.  This was the technique employed,
          e.g., in the Coast Guard's Chemical Hazard
          Ranking Information System  (CHRIS). (6)

      A structure for classification of existing systems by utility and
a structure for  classification by design of the prioritization/categori-
zation system have been presented. A representative sample of exist-
ing systems within the framework of these structures is presented to
illustrate the structure.
"Wise Man" Approach
      A classic example of the wise man approach is given by the
National Pesticide Monitoring Program.   The NPMP consists of an
integrated interagency effort to restrict, control,  and monitor the
pesticides and their decay products in the environment.  The program
consists of three basic functions.

      (1)   Criteria — developed by published information,
           company data,  brainstorming
                                 139

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       (2)  Registration - to control the quantity of
           pesticides entering the environment

       (3)  Technical Services - to  develop monitoring
           techniques and to coordinate the efforts of
           the many environmental  monitoring programs
           currently in existence.

 The program is structured around  a list of pesticides and trace metals.
 The list was constructed via a collective  set of opinions, based on
 toxicity,  quantity, and persistence.  Local monitoring programs are
 free to exercise their  own judgment on which pesticides are monitored.
 f'Index" Approach

      An index can be constructed by two methods.  In a stochastic
 construction,  statistical techniques are used to derive indices from a
 wide variety of data or observations.  A large amount of data is gen-
 erally required for the stochastic approach.  The deterministic con-
 struction identifies or deduces (subjectively) relevant indices from
 the area of concern.  The indices may be algebraic and/or logical
 combinations of data.  Frequently an index may have a physical
 meaning.
      Stochastic Index.  In 1971, Synectics Corporation developed a
 system for industrial waste treatment RD&D project priority alloca-
 tion.  In this study, three priority indicators were derived by the
 stochastic technique from existing, implicit EPA priorities.

      Each of the indicators was derived by the utilization of past
 Federal funding to provide rank order as a dependent variable.  The
 independent variables for the three indices (location, constituent,  and
 industry) are presented in Table 3.  A statistical technique was used
 to derive the three indices from the gathered data.  These indices
 were then utilized to prioritize future EPA expenditures by state and
by industry.

      The scheme presented by Synectics typifies the construction of
a stochastic index to perform prioritization.  The data utilized to
construct the index (Federally funded),  however, must be viewed as
subjective data  representing at best the consensus of experts.
                                  140

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      Deterministic Index.  Many examples of deterministic indices
are available.  One  such study was performed by Battelle for the/4x
Consumer Protection and Environmental Health Service (CPEHS)'   ,
later separated into two agencies, and ultimately disbanded.  A con-
ceptual system was  derived to examine research and development
program planning needs, and to develop a management assistance
program.  The study itself can be categorized into the  II. B category
of Table 1, while the prioritization scheme is based on a determinis-
tic index.

      Problem identification from the perspective of environmental
stressors and priority setting were determined to be important func-
tions to be performed in the  planning cycle.  No single method for
planning and priority setting was found to be totally applicable to the
mix of complex problems encountered by CPEHS.  Continuation of
categorical planning activities was recommended to serve as the
foundation for the development of an integrated  planning system based
upon quantitative assessments of the  impact of technology upon man
and his environment.  Full implementation of the integrated planning
system requires  the availability of a  hierarchy  of mathematical models
for the assessments.

      Demonstration of the integrated planning system concept was
provided through case studies for lead and DDT, and for lead, a
preliminary identification  of elements to be included in a partial
program plan was made.

      The concept of Urgency as a means to establish priorities for
EHS was investigated.  The" Urgency  consists of the people affected,
the severity of the effect,  and the rate of change of these quantities
with time*

      A priority index was formed based upon the average Urgency
value during a planning horizon, where Urgency was defined as the
product of severity and population at  risk.  The calculation of Urgency
can be weighted and summed over each population at risk to provide
an estimate of total Urgency.  It was illustrated that Urgency could
be discounted in time.

      As the study did not  have the data to perform priority ranking,
and such data would not be available  to CPEHS  for several years after
implementation,  the ranking was never performed.  An intermediate
alternative method was proposed, however.  This was in essence a
"wise man" approach, utilizing value judgments from  experts.
                                   141

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               TABLE 3. INDEPENDENT VARIABLES FOR STOCHASTIC INDICES
                       IN EPA PRIORITIZATION OF FUNDING
        Locational               Effluent Constituent           Industrial Volume
      (State as Case)              (State as Case)          (SIC 2-Digit Code as Case)

Industrial waste-water volume      Effluent volume             Industrial effluent volume
Population                    State standard              Water use
Valve added by manufacturer      Economic effects            Valve added by manufacturer

Annual runoff                 EPA regional standard        Employment
Water area                    Public notice               Number of states with plants
Population density               Low concentration limit       Total plants

Industrial water use              High concentration limit      Plants using >20 mgy

                            Relative cost of removal
       Other examples of deterministic indicators are available.   These
include

       (1)  A water hazard ranking scheme (Figure  1) which
           utilizes volume transported,  accident probabilities,
           and critical concentrations to provide a rank based
           upon the expected volume of water polluted to the
           critical concentration annually. **'

      (2)  A solid waste hazard screening system (Figure 2)
           which classifies a material as very hazardous if
           the material meets  any one of eleven criteria.
           This is an example  of a logical (as opposed to
           algebraic) indicator.

      (3)  An air hazard ranking scheme  analogous to (1)
           above,  but including stationary sources.
           Stationary sources produced an index based
           upon a record of accidents with arbitrary
           scoring, while mobile sources produced an
           index analogous to (1) above,  but with con-
           siderations of voUtility and hazard ratings.
           The two indices were combined logarith-
           metically to produce a hazard ranking index,
           for accidental air pollution episodes.


                                    142

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                                         X
                                      CRITICAL
                                    CONCENTRATION
                                 REQUIRED VOLUME TO
                              DILUTE EXPECTED SPILLAGE
        V -
                  R
                                              QT)/X
 EXPECTED AKXUAL
SPILLAGE BY  BARGE
    SHIPMENTS
                                          _ RANKING
                                          "PARAMETER
           EXPECTED ANNTJAL
          SPILLAGE BY RAIL
              SHIPMENTS
 EXPECTED ANNUAL
SPILLAGE BY TRUCK
    SHIPMENTS
                                  ANNUAL PRODUCTION
                                FRACTION TRANSPORTED
                               ACCIDENT PROBABILITIES
          FIGURE 1.
GRAPHIC REPRESENTATION  OF HAZARDOUS
WATERSORNE SUBSTANCES MODEL
                                          143

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                         Candidate Waste
                 True
                  True
                   True
Classes II and
III Waste
                                      Class I
                                     Hazardous
                                      Waste
FIGURE 2.
         GRAPHIC REPRESENTATIVE OF THE
         HAZARDOUS WASTE DECISION
         MODEL
                   144

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      (4)  The Office of Water Programs has developed a
          list of hazardous  substances based upon a logical
          deterministic index.   Data considered include
          half-life,  bioconcentration, radiotoxicity,
          lethality (in aqua, oral, dermal,  vapor), oxygen
          demand, and nuisance-aquatic growth stimulation.

      (5)  NIOSH provides each  year a priority list for
          Criteria Development for Toxic Substances and
          Physical Agents.  The 1972 list was based
          upon a system developed by the staff of the
          former  Bureau of Occupational Health and
          Safety.  Five indicators, namely

          (a)  Population at risk, based on walk-
              through surveys of industrial work
              forces

          (b)  Relative toxicity,  a rank score
              based upon expert opinion
          (c)  Incidence  of disease, from occupa-
              tional records

          (d)  Quantity of production
          (e)  Trend of production quantity were
              combined to produce  an index of
              priority.
          The 1973 priority list was obtained in a similar manner,
          except that the indicators were slightly different.  The
          population at risk, quantity of production,  and trend
          were  combined to produce expected exposure for a
          given time frame. The relative toxicity and disease
          incidence  items were discarded in favor of a  sub-
          jective assessment of the combination of likelihood
          of disease and severity, derived by a Delphi technique
          from  the opinions of fifty occupational health
          professionals.
"Optimized" Approach

      The Coast Guard  CHRIS system is an example of the optimized
approach.  The CHRIS (Chemical Hazards Response Information
                                  145

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 System) study was performed by A. D.  Little, Inc. , in 1972, to pro-
 vide a response system to the  spillage of hazardous waterborne
 materials.
       The study contains an analysis of information requirements for
 the five stages of a spillage incident,  namely

       (1)  Detection, evaluation, notification
       (2)  Containment and countermeasures
       (3)  Cleanup,  disposal
       (4)  Restoration
       (5)  Adjudication.

 A tentative list containing some 144 perceived information needs was
 generated (a laundry list).  This list was truncated to 78 elements by
 subjective elimination and aggregation. The list then contained eight
 major categories:

         (I)  Chemical (16 elements)
        (II)  Shipping and Carrier *f8 elements)
        (III)  Environment (16 elements)
        (IV)  Resource (8 elements)
        (V)  Incident (13 elements)
        (VI)  Procedures and Background (4 elements)
       (VII)  Hazard Evaluation (7 elements)
      (VIII) Response Model (6 elements).

 Nine categories of information users were defined, as were three
 actions of users and four media by which information could be
 provided.

       Subjective analysis then provided further variables.  A score of
 0 to 5 was provided as a consequence  of a  wrong decision by each of
 the nine users based on each of the 78 information elements.   An
 incremental reduction in the likelihood of the wrong decision by each
 of the nine users due to the provision  of each information element
 was subjectively assessed.  A weighting factor was provided to
 modify the consequence of each wrong decision by the action of the
 user.  A RCR score (Risk Consequence Reduction) was then computed
 for each information element — user pair.

      In this manner the information needs of CHRIS were prioritized.
 It was found,  for example, that the top nineteen information elements
 provided a 50 percent reduction in RCR.  The most critical informa-
tion elements for each phase could also be determined with this


                                  146

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technique.  It should be emphasized, -however, that the prioritization
is based upon subjective data.
                   Prioritization in Early Warning
      Many existing systems for identifying and evaluating chemicals
which are potentially hazardous have been identified.  An improved
early warning system would incorporate many of these existing sys-
tems as  components, but the specific form of the early warning sys-
tem will be at least partially dependent upon the prioritization or
screening of chemicals which must take place before committing
resources  to detailed assessment of toxic hazards.

      The state  of the art of prioritization schemes for hazardous
chemicals  has been shown to be quite limited.   In  short, these limita-
tions include

      (1)  The liberal utilization of  subjective data
      (2)  The availability of only three algorithms for
          prioritization.

As the state of the  art of prioritization is limited, so must be its
application to an early warning system.  Within these limitations,
it is fairly straightforward to devise prioritization schemes  for an
early warning system.

      Three approaches for prioritization of chemicals and classes
of chemicals, covering the range of the state of the art, are discussed
here.  These are presented with the recognition that perfect screen-
ing is impossible,  that much data (particularly for new compounds)
may be missing, and that the  screening process must be relatively
simple if it is to be applied to  a large number of chemicals.

      The first would utilize the wise man approach as,  for  example,
used in the  National Pesticide  Monitoring Program.  A list of candi-
date chemicals would be derived from the consensus of informed
experts.   The list of experts should be quite large, as many disci-
plines should be  represented.  The  effort to generate the original
list would be large, but the list could be periodically updated for far
less effort.  The resulting list would be, in essence, completely
subjective.
                                  147

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       The list of chemicals to be screened would not be formal.
 Rather, it would be encumbent upon the experts to provide  "pre-
 screened" compounds (for judgment by the consensus) from the liter-
 ature available to the experts.  It would be desirable to provide  an
 adequate data base for utilization by the experts throughout the
 screening process.

       In the second approach, an index could be constructed to per-
 form prioritization.  Such a technique applicable to organic chemicals
 based on a stochastic index has been proposed*'':  it could  be  extended
 to others.  The  variables of the index would be selected subjectively.
 The  difficulty with this approach is that an index which allows screen-
 ing with a degree of reliability would require data that is unavailable
 for many of the  chemicals to be screened.  The subjective  data
 required for the  screening may weaken the reliability of the results.

       If a stochastic index is constructed it may be desired to con-
 struct indices on subsets of the independent variables.  For example,
 a discriminant analysis for screening variables might be performed
 for the entire set of independent variables as well as subsets. Dis-
 criminant screening of chemicals with missing data would then require
 the application of the discriminant function appropriate to the  available
 data. Needless  to say, a significant amount of data from case studies
 would be required to derive stochastic indices.

       In the  third approach,  a detailed laundry list of desired  informa-
 tion for screening would be considered. A scheme would be derived to
 evaluate the worth of each element to the screening process,  consider-
 ing the cost  of errors in an early warning  system, as well  as  the cost
 of obtaining  the information.  In this manner the most cost-effective
 information  elements for a  screening process  would be derived.   The
 information  items could then be combined  as in the second  approach
 to perform the screening.
                            CONCLUSIONS
      Numerous systems exist which have as their objective the iden-
tification of adverse chemical effects on human health and/or the en-
vironment. Nearly all have been formulated within a relatively nar-
row framework of applicability or use; as  such, they are not readily
adaptable to the needs of EPA's Office of Toxic Substances (OTS).
Nevertheless,  many of these systems could represent important

                                   148

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adjuncts to any OTS efforts to monitor public exposure to various
chemicals.  For example, many of these systems have well estab-
lished sensor networks which are valuable early indicators of problem
substances.

      Existing systems can be classified in several ways.  Early in
the program it became apparent that a major system class was the
information repositories for chemical data - especially toxicity data.
These information centers are numerous,  frequently provide automated
storage and retrieval, and generally have  a defined albeit limited scope.

      Systems other than information centers can be classified with
respect to whether their principal function is to identify chemical sub-
stances before general exposure of the public and environment occurs
(input surveillance),  or after such occurs  (output surveillance).  Each
of these  types can be further subcategorized into those which basically
seek to identify new or unrecognized chemical stressors and those
which seek to evaluate the hazard of a recognized stressor.

      Systems differ in the manner in which a candidate list of sub-
stances for evaluation is identified and comprise (1) systematic litera-
ture scanning, (2) licensing, (3) test protocols, (4) expert panels,
(5) data base sampling, accumulation, or analysis, (6) incident reports,
etc.  Conversely,  an examination of the design basis of existing sys-
tems  suggests only a few basic  approaches for asses sment/prioritiza-
tion (or categorization) functions.  Three of these  are the use of
experts, a numerical index of measure or hazard,  and subjective
weighting factors or assigned values for selected parameters felt to
be of importance.

      Finally, it is possible to utilize this knowledge of existing sys-
tems  to conceptualize three potential designs for a prioritization/
classification scheme.  As with most existing systems,  the three
designs rely heavily upon subjective input.
                           REFERENCES
(1)  Flinn, J. E., et al.,  "Literature Search and State of the Art
     Study of Identification Systems for Selecting Chemicals or
     Chemical Classes as Candidates for Evaluation", Battelle's
     Columbus Laboratories report to USE PA, Office of Toxic
     Substances,  NTIS Report No.  PB-238 196 (November 1974).
                                   149

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(2)  "A Directory of Information Resources in the United States -
     General Toxicology", compiled by the Library of Congress for
     the National Library of Medicine  (June, 1969).

(3)  "The Toxic Substances List,  1973 Edition", H.  E. Christensen,
     Ed., U. S. Department of Health, Education, and Welfare (June,
     1973).

(4)  Morrison, D.  L.,  et al.,  "Technical,  Intelligence, and Project
     Information System for the Environmental Health Service", Vol.
     I-V,  HEW Contract GPS 69-005 (1970).

(5)  Dawson, G.,  et al., "Control of Spillage of Hazardous Polluting
     Substances",  Study for EPA by Battelle Memorial Institute's
     Pacific Northwest  Laboratories (November, 1970).

(6)  Coast Guard CHRIS, "Preliminary System Development -
     Chemical Hazards  Response Information Center", Study for U. S.
     Coast Guard Office of Research and Development by A.  D. Little,
     Inc. (May, 1972).

(7)  Howard, P. H., "Establishing Environmental Priorities for
     Synthetic Organic Chemicals Focusing on the Next PCB's",
     presented at the Seminar on Early Warning Systems for Toxic
     Substances, Seattle, Washington (January,  1974).
                                 150

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      A RESEARCH PROGRAM TO ACQUIRE AND ANALYZE
        INFORMATION ON CHEMICALS THAT IMPACT
                ON MAN AND HIS ENVIRONMENT

                        Arthur A. Me Gee
                      Kirtland E.  McCaleb
                   Stanford Research Institute
                     Menlo Park,  California
                           ABSTRACT


      SRI has developed a system to collect, analyze,  and systematize
information on the chemical description, production, uses and human
exposure of chemicals with which the U. S. population comes in contact.

      This effort provides  information to aid the National Cancer
Institute Carcinogenesis  Program in selecting chemicals to test to
which the U. S.  population is exposed.  The criteria used by NCI's
Chemical Selection Committee for selecting chemicals for carcinogenic
testing are:

      •  The degree of overall human exposure

      •  Projected new or increased human exposure
      •  Exposure of subpopulations important to society
      •  Epidemiological clues (high cancer incidence
        subpopulations)

      •  Relation to known carcinogens
      •  Gaps in knowledge.

The present data base contains information on 3, 200 chemicals in the
following categories:

      Intentional food additives         Air pollutants
      Pesticide  residues in food        Water pollutants
      Proprietary drugs                Soaps and detergents
      Prescription drugs              Trade sales paints
      Cosmetics

      •  The establishment of an "early warning" surveillance
        system to detect new chemicals coming into use, increased

                                 151

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         use of existing chemicals, and new uses of existing
         chemicals that will lead to increased human exposure
       • Breaking out estimates for present exposure categories
         to reflect per capita and per weight exposure estimates
         for important subpopulations
       • Further work in representing structure-activity
         relationships
       • Refining exposure factors used in estimating human intake

       • Including data on high risk subpopulations
       • Enlarging the data base to include other chemical,  physical,
         and biological information
       • Expanding the data base to include additional exposure
         categories and classes of chemicals
       • Reprogramming the  data processing system to handle a
         larger data base and to respond to a greater range of
         inquiries
       • Expand the use of the system to serve an expanded set of
         objectives serving other groups within NCI and other
         agencies with regulatory and standard-setting responsi-
         bilities concerned with health hazards arising from
         exposure to chemicals.

 These categories are subdivided into 900 product types representing
 18, 000 chemical-product combinations.

      The data are in computer-readable form and  contain the follow-
 ing information:

 	Product	             Each Ingredient Chemical
 Product name                         CAS number and name
 Quantity available for exposure        Strength (percent) in each
                                         product
 Exposure routes— oral, dermal,       Degree of uncertainty associated
  respiratory, and parenteral            with quantitative data

Exposure factor by route               References to data sources

      In addition to the  information on the 3, 200 chemicals in the above
nine exposure categories, a data bank of approximately 25, 000 chemi-
cals has been developed which includes many of the substances to which

                                 152

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the human population is most likely to be exposed.  These chemicals
were drawn from eighteen recognized sources of information on such
products as cosmetics, food additives, medicinals, etc.  For each of
the 25, 000 chemicals in this data bank, the CAS number, structure,
chemical name, and synonyms are stored in computer readable
form.

      A computerized chemical classification scheme has also been
developed that contains 220 nodes  or  end points.  This development has
allowed a node  assignment to be made for each of the chemicals for
which exposure estimates have been made.  As additional biological
data become available it may eventually be  possible to make informed
guesses as to a molecule's  carcinogenic potential based on such a
chemical classification scheme.

      In addition to providing the Chemical  Selection Committee with
information based upon the  existing data base,  a number of develop-
mental tasks are either under way or under consideration including:
                                 153

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       NATIONAL CANCER INSTITUTE PROGRAM OF CANCER
             SURVEILLANCE, EPIDEMIOLOGY AND END
                RESULTS REPORTING (SEER Program)

         James  L. Murray, D.V.M. and Sidney J. Cutler, Sc.D.
              Biometry Branch, National Cancer Institute,
                          Bethesda, Maryland
                              ABSTRACT
       The SEER Program provides information on trends in the
 incidence of the various forms of cancer in the United States,  varia-
 tion in the occurrence of cancer  among different population groups
 and in different geographic areas, changes in diagnostic and treat-
 ment practices and the associated end results  in the general run of
 cancer patients.  Data are obtained from a selected number of
 population-based cancer registries that provide uniform information
 on a continuing basis and these registries participate in ad hoc studies
 designed to identify and assess etiologic and prognostic factors.

       The SEER Program contributes to Objective No.  5 of the
 National Cancer Plan, i.e.,  "develop the means to achieve an
 accurate assessment of (a) the risk of developing cancer in groups
 and in individuals and (b) the presence, extent and probable course
 of existing cancers".
                           INTRODUCTION
      As the National Cancer Program develops, it is becoming
increasingly evident that a variety of program elements and program
participants relate to and are concerned with the collection, analysis
and utilization of data on the incidence of cancer,  the characteristics
of patients and their disease, treatment  and  end results. No one
organization can or should attempt to exercise primary control over
the broad variety of data required to meet the needs of the many
participants in the  National Cancer Program.  However, it is highly
desirable for organizations and institutions with a primary interest
in data collection,  analysis and utilization to be aware of one another's
activities and interests.

                                 154

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                  SEER PROGRAM PARTICIPANTS
      The National Cancer Institute is sponsoring a program of
Cancer Surveillance, Epidemiology and End Results Reporting (SEER),
This program is being coordinated by the Biometry Branch, Division
of Cancer Cause and Prevention and is an outgrowth of the End
Results Evaluation Program,  which has been in operation since 1956,
and the Third National Cancer Survey which covered the three year
period 1969-1971. (1) It is designed to support the National Cancer
Plan and help achieve Objective Number 5 which is to  "develop the
means to achieve an accurate assessment of (a) the risk of developing
cancer in groups and in individuals and (b) the presence,  extent and
probable course of existing cancers".

      The SEER Program involves the collaboration of two types of
participants:

      (a)  Population-Based Tumor Registries
          These registries have reporting systems designed to
          obtain information on every newly diagnosed case of
          cancer (except nonmelanotic skin cancer) and on
          every death with cancer, among members of a de-
          fined population, usually one to three million people.
          The  cooperation of every general hospital and of the
          state office of vital statistics is necessary  to assure
          completeness of reporting.
          The  goal is to produce reliable and timely data on
          the incidence of cancer among  the residents of the
          area to  provide information on changes over time and
          on variation in the occurrence  of cancer among sub-
          groups of the population.
          All,  or  a majority of the hospitals, participate in a
          patient follow-up system to provide information  on  end
          results, i.e., the relationship of patient survival to
          the characteristics of the patient,  the nature of the
          tumor,  extent of disease at diagnosis,  and  treatment.

          The  collected data are utilized to identify issues that
          warrant investigation through special studies,  which
          may be  carried  out within  a single geographic  area
          or as a  collaborative project in two or more areas.

          In selecting areas for inclusion in the SEER Program,
          a number of factors are considered,  including:

                                 155

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           (1)  Geographic dispersion to provide for a
               variety of environmental and industrial
               settings,  and a variety of racial, ethnic
               socioeconomic population groups.
           (2)  Availability and interest of appropriate
               professional and technical personnel
               associated with an appropriate local
               sponsoring organization.
           (3)  Interest and support of the local community,
               including the hospitals,  practicing physicians,
               and both public and voluntary organizations.

       (b)  Epidemiology Research and  Training Centers
           A selected number of areas  with population-based tumor
           registries are being assisted in the development of
           broad programs of epidemiologic research and train-
           ing.  Such programs require active participation of
           educational institutions with senior staff experienced
           in planning and carrying out epidemiologic and related
           research  in cancer and other chronic diseases. The
           availability and interest of specialists in a variety of
           medical and scientific disciplines, who will participate
           in different studies, is of primary importance.

           A principal goal is the development of research pro-
           grams that provide a means for attracting talented
           young people for on-the-job  training in cancer
           epidemiology and related skills, supplemented by
           appropriate related academic studies.

       The current participants are shown in Table  1.  These nine
 registries cover defined populations totaling almost 10% of the United
 States population.  A few other areas of the country are being con-
 sidered,  but complete coverage of the  United States is not considered
 necessary or feasible at this time.  In order to provide current data
 on cancer incidence, the  registries will submit their incidence data
 for each calendar  year to the National  Cancer Institute  annually
 within 12 months of  the end of each year.  In addition, a complete
 data file including current follow-up information on cases diagnosed
 during a specified calendar period will be submitted every two years.

      Although cancer incidence statistics are not available for the
 entire country,  complete cancer  mortality data are collected by the
National Center for Health Statistics and are available on an individual
                                 156

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               TABLE 1.  SEER PROGRAM PARTICIPANTS
      Contract Agency
     Area Covered
  Population
Covered - 1970
California State Department
of Health
Connecticut State Department
of Health

Fred Hutchinson Cancer
Research Center
University of Iowa
Louisiana Health, Social and
Rehabilitation Services
Administration

Michigan Cancer Foundation
University of New Mexico

Research Corporation of the
University of Hawaii
University of Utah
Alameda, Contra Costa,        3,109,519
Mariri, San Francisco, and
San Mateo counties
Entire state of Connecticut     3, 031, 709
King,  Kitsap, Pierce          1, 934, 628
Snohomish and Thurston
counties, Washington
Entire state of Iowa            2, 824, 376
Jefferson, Orleans and           982,224
St. Bernard parishes,
Louisiana
Macomb, Oakland and          4,199,931
Wayne counties, Michigan
Entire state of New Mexico     1, 016, 000

Entire state of Hawaii            768, 561

Entire state of Utah            1,059,273
                   TOTAL   18,926,221
county basis.  Counter balancing the  advantages of having mortality
data for the entire country is the fact that the relationship between
the number of cancer deaths and the number of newly diagnosed
cases of cancer varies among the different forms  of cancer and also
by race, sex,  age,  socio-economic status,  and calendar time.  Thus,
sole reliance on mortality data may  lead to erroneous conclusions
and invalid comparisons.

       The cancer incidence data produced annually by the SEER
Program will  be a great improvement over that previously available.
Besides the Third National Cancer Survey which covered 1969 through
1971,  the  only other national surveys were the two Ten Cities Sur-
veys  of  1937 and 1947.^)  The large gaps in our data  base for the
                                 157

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 time intervals between surveys are filled only partially with annual
 data from the Connecticut Tumor Registry which started in 1935. t3'
 The Connecticut data have been very useful for assessing the trends
 suggested by the three survey data points.  There is considerable
 interest in trends in the occurrence of cancer because of their
 usefulness in

       (1)  Identification of leads regarding the impact of changes
           in the environment and in human behavior,
       (2)  Assessment of the impact of cancer control programs,
           such as anti-smoking  campaigns and exfoliative
           cytology,  and
       (3)  Measurement of changes in the magnitude and nature
           of the cancer problem for planning the allocation and
           development of resources.

       Since we have  three sources of data regarding long term trends
 in cancer  occurrence in the  United States, it is of interest to see
 whether a consistent picture emerges and whether observed incon-
 sistencies can be rationalized.   Trends in mortality reflect the
 interplay of  two factors, namely, the rate of incidence and  the
 patient survival rate.  The most comprehensive data available on
 patient survival has  been compiled by the End Results Evaluation
 Program sponsored  by the National Cancer Institute.  The latest
 report contains survival data on more than half a million cases of
 cancer diagnosed during the period 1940-1969. ^  This program is
 now an integral part of the SEER Program.
          LONG-TERM TRENDS IN CANCER OCCURRENCE
      For all sites combined,  different trends can be seen for males
and females.  Among males, both incidence and mortality have been
increasing continuously since at least 1935.  The increase has been
particularly large among blacks, but this may be partially a reflec-
tion of improvement in the delivery of medical care resulting in
more complete diagnosis of the disease.  It is likely, however, that
a substantial fraction of the  reported increase reflects the impact
of environmental factors, such as movement from rural to urban
areas and concentration in inner cities, changes in occupation,  and
changes in eating, drinking and smoking habits.  Among females,
                                158

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very little change can be seen for black women since 1935,  but white
women have experienced a slight decrease.

      Ail measures point to large continuous increases in lung cancer,
as shown in Figure 1.  Over the total period from 1935 to 1970, the
increase among men was much larger than among women.   As a
result of the sharp rise in the reported  occurrence of lung cancer
in the black population,  the  incidence rates  (adjusted for age) for
blacks are now higher than for whites, particularly among men.

      The greatest difference  in cancer occurrence between the races
is in cancer of the esophagus, as shown in Figure 2.  In the white
population there have been minor fluctuations in occurrence over
the years,  but no appreciable  increase or decrease.  In the black
population, however,  sharp increases can be seen in both incidence
of and mortality from esophageal cancer. As a consequence, the
incidence rates in the black population are now much higher than
in the white - rates of 15. 1 versus 4. 1  in men and 3.2 versus 1.2  in
women.  The extent to which the marked rise in reported incidence
and mortality in the black population reflects more complete case
finding due to increased availability of medical care is not known.
However, it is  clear that  esophageal cancer is now a sustantial health
problem among blacks.  The decreased incidence of esophageal
cancer in white men during the 1960's is intriguing and should be
studied  in conjunction with the continued increase in incidence among
black men.  Can these divergent trends be explained by the same set
of factors, such as changes in occupational  exposure or changes in
alcohol  consumption?

      Figure 3  shows that all measures point to an increased trend
in cancer of the pancreas,  but with marked  variations in magnitude.
In the white population,  the increases in both incidence and mortality
rates were higher in men than in women. They were also higher in
the black population than in the white.  It seems likely that at least
part of the large reported increase in the occurrence of pancreatic
cancer in the black population is due to more frequent identification
of the disease as a result of increased availability of medical care.

      The incidence of and mortality from cancer of the uterus have
decreased in both black and white women, as shown in Figure 4.
The incidence data indicate a  somewhat larger decrease among
blacks,  whereas the mortality data indicate a larger decrease in
whites.   The data presented pertain to all cancers of the uterus,
except carcinoma in situ of the cervix.   In examining trends,  the


                               159

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  •0
  40
o
§,„
                     LUNG
    .  WHITE MALES
«  « NCI INdDIMCI
•——• U I. MORTALITY
*-	• COMHCTKUT ntCIDIMCI
0—0 COtWCTICUT MORTALITY
i


I"
BLACK MALES
     NCI WCIDCNCf
     U.I. MOHTAUTV
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     t  . NCIINCIDINCI
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                                                  WHITE FEMALES
                    WIO
I

§

» 20
BLACK FEMALES

.   « NCI INCIDENCI
»   » U.I. MORTALITY
    FIGURE  1.
              LUNG;  TREND OF CANCER INCIDENCE AND
              MORTALITY  RATES,  1935-1969 (AGE-
              ADJUSTED,  1950 STAMDARD POPULATION
              Note:. Different scales used for males and
                      females.
                                        160

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15
M
              ESOPHAGUS
  L WHITE MALES
—_. NCIINCIDINCI
—• U.t. MOKTAUTV
—•• CONNICTICUT INCIOENCI
	-O CONNECTICUT MORTALITY


IS
  _ BLACK MALES
         NCI INCIDINCI
   Ti3S
                                                      ESOPHAGUS
                                                WHITE FEMALES
.	»  NCI IMCIDIMCt
»  »  U.I. MORTAIITY
•	.  coHNicneuT IMCIOIHCI
0—0  CONNICTICUT MORTALITY
                                      2
                                      S
                                      O
                                      1*
                                                 BLACK FEMALES
  FIGURE 2.  ESOPHAGUS:  TREND OF CANCER INCIDENCE AND
                MORTALITY RATES,  1935-1969 (AGE-AD JUS TED,
                1950 STANDARD POPULATION
                Note:  Different scales used for males and females.
                                       161

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3
                    PANCREAS
      WHITE MALES
       - » NCI INCIDENCE
          • U.I. MORTALITY
       --- • CONNECTICUT INCIDENCE
            CONNICTICUT MOHTUITV
       -- -O
                             I      I      I
      BLACK MALES
           NCI INCIDENCE
                                                               PANCREAS
- WHITE FEMALES

   »   . NCI INCIDENCE
   »   » us MOKTAirry
—  •	i CONNECTICUT INCIDENCE
   0—0 CONNECTICUT MORTALITY
                                                    BLACK FEMALES
                                                         NCI INCIDENCE
                                                         U I MORTAIITV
                                  neo
                                                                    1*60
FIGURE 3.  PANCREAS:  TREND OF CANCER INCIDENCE AND
                 MORTALITY RATES,  1935-1969 (AGE-ADJUSTED,
                 1950 STANDARD POPULATION
                                           162

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       100
        78
        BO
      S
      S"
      §
      O
      o

      £ too
      a.
        75
        BO
        28
                     UTERUS  (TOTAL)
-  WHITE FEMALES
*	* NCI INCIDENCE
•   • U.8. MORTALITY
*	A CONNECTICUT INCIDENCE
0-~o CONNECTICUT MORTALITY
                          NCI INCIDENCE
                          U.S. MORTALITY
           1MB
                             18SO
                                         I860
                                                     1970
FIGURE 4.  UTERUS: TREND OF CANCER INCIDENCE AND
             MORTALITY RATES, 1935-1969  (AGE-
             ADJUSTED,  1950 STANDARD POPULATION

             Note: Includes invasive cancers of all .parts of
                   the uterus.  Excludes carcinoma in situ.
                               163

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 data for uterine cervix and corpus have been combined because
 medical records often do not contain sufficiently specific information
 to separate them.   The decreases in both incidence and mortality
 have been continuous since the late  1930's.  Thus,  the downward
 trend began well before the advent of cervical cytology screening
 programs in the mid-1950's.
       Figure  5  shows the trends for cancer of the bladder.  The sur-
 vey data point to increases in incidence in both white and black males
 and decreases in both white and black females.  The Connecticut
 data, which pertain mainly to whites,  indicate increases in both
 sexes,  but the increase in males is  much larger than in females.
       Present knowledge  indicates that many types of cancer are
 associated with environmental factors,  and a majority of cancer
 deaths is attributable to them. The estimated cancer deaths in the
 United States for 1973 are shown in Table 2 along with an estimate
 of the extent to which they are attributed to environmental factors.
               TABLE 2.  ESTIMATED CANCER DEATHS IN USA
                         FOR 1973 (BOTH SEXES)
       Site
                Total Deaths   Extent Attributed to Environmental Factors
 Lung

 Colon-Rectum
 Pancreas
 Leukemia
 Stomach
 Bladder

 Oral Cavity
 JLiver (Primary)
Esophagus
Skin
Larynx
   Total These Sites
   Other Sites
                  72, 000

                  47, 400
                  19,200
                  15,300
                  14,700
                   9,200

                   7,600
                   7,200
                   6,400
                   5,200

                   3,000
                 207.000
                 143,000
TOTAL All Sites   350,000
++++ Tobacco, Asbestos, Air Pollutants,
       Occupational
+++  Diet, Other Environmental
++?  Tobacco, Diet(?)
+    Radiation, Chemicals
+++  Diet, Other Environmental
+++  Occupational, Tobacco, Diet(?)
       Other Environmental
++   Tobacco, Chemicals,  Diet(?)
++   Diet, Other Environmental
++   Environmental
++++ Ultraviolet Light,  Chemicals,
       Occupational
+++  Tobacco, Air Pollutants
+, ? (Includes Hormonal Factors)
                                     164

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M
  . WHITE MALES
                BLADDER
  L  BLACK MALES
                    •—« NCIMCIDINCt
                    •——• U.I. MO«T*UTY
                    «—. caMiieneuT INCIDINCI
                                                        BLADDER
                                             WHITE FEMALES
IM. MOMTAlfTY
                        NCI INCIDINCI
                        U.I. HOIITAUTY
                                             BLACK FEMALES
                                                               U.C.MOKTMITV
                            1MO
                                                                     ISM
FIGURE 5.  BLADDER:  TREND OF CANCER INCIDENCE AND
               MORTALITY RATES,  1935-1969 (AGE-ADJUSTED,
               1950 STANDARD'POPULATION
                                     165

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For many types of cancer, specific etiologic factors have not yet
been clearly identified,  but they may well contribute to the pool of
environmentally caused cancers. A large group of cancers is related
to endocrine factors,  which are not environmental per se,  although
they can be influenced by exogenous  factors, including intake  of
hormonal preparations.

      Cancers are known to have widely varying induction times, some
ranging up to 30 or more years.  The shortest induction times are
found in children with acute leukemia and cancers of the brain and
nervous system.  We need to learn much more about the induction
times of specific types of cancer and the factors influencing the
growth rate of the  developing tumor.

      If we do not have adequate data on exposure to carcinogenic
agents  at the  time  of exposure,  our first lead may come from the
induced neoplasms when they are diagnosed clinically.  The SEER
Program will provide measures of increased  cancer occurrence in
specific subgroups of the population. These leads can then be followed
retrospectively to  determine the causative factors  and hopefully
prevent further occurrence of the disease.
                            REFERENCES
 1.   Cutler,  S.  J., "Report on the Third National Cancer Survey",
     Proceedings of-the Seventh National Cancer Conference, J. B.
     Lippincott Co. (1973), pp 639-652.

2.   Dorn, H. F.,  and Cutler, S. J., Morbidity from Cancer in the
     United States,  Part I and Part II combined, U. S.  Dept. of Health,
     Education,  and Welfare, Public Health Monograph 56.  Govern-
     ment Printing  Office, Washington,  D.C. (1959), 207pp..

3.   Cancer in Connecticut,  1935-62, Connecticut State Department of
     Health,  Hartford, Connecticut,  1966.  More recent data have
     been provided  by Dr. Barbara Christine,  Director,  Connecticut
     Tumor Registry.

4.   Axtell, L. M., Cutler,  S. J.,  and Myers, M.  H., End Results
     in Cancer,  Report No. 4, National Cancer Institute, Bethesda,
     Maryland, DHEW Publication No.  (NIH) 73-272 (1972).
                               166

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            ENVIRONMENTAL IMPACT OF CHEMICALS

                       Robert J. Moolenaar
                    The Dow Chemical Company
                         Midland, Michigan
                            ABSTRACT
      The early assessment of the impact of chemical products on the
environment is of vital importance to the chemical industry.  Most
programs in existence in the chemical industry for evaluating the
environmental impact of products depend upon laboratory testing and,
based on the results of those tests, the subsequent prediction of envi-
ronmental behavior.

      Laboratory tests begin with a determination of basic physical,
chemical and biological properties of the specific chemicals contained
in the product.   Depending on the results of the simple tests and the
anticipated uses and production volumes, more sophisticated evalua-
tions may be required.  The  environmental behavior of a chemical is
predicted in terms of its lifetime,  movement, bio concent ration poten-
tial, and spectrum of biological activity.  Appropriate guidelines for
handling, use and ultimate disposal of the products are drawn from the
assessment of environmental behavior.

      The validity of the early assessment is constantly monitored by
actual observation of the effects of chemicals in the real environment.
This is  done both by monitoring the health of people exposed to chem-
icals, and by monitoring the  environment around the manufacturing
plant.
                          INTRODUCTION
      A few years ago the Council on Environmental Quality reported
that there were about 9, 000 synthetic organic chemicals in commerce,
Most  of them are used in very small quantities, but a significant
number are major products that play a vital role in our society.
Virtually every product now used by man is in some way impacted
by one or more of these  chemicals.  Since many of these compounds
                                 167

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 are foreign to the biosphere, the development of techniques for predict-
 ing and evaluating potential harmful effects caused by their release to
 the environment is of great value to society.  For this reason,  I
 welcome the opportunity to discuss the program in effect in my company
 which I believe is effective in attaining the goals of an early warning
 system for toxic  substances.
         METHOD OF EVALUATING IMPACT OF CHEMICALS
       I am going to discuss how we evaluate the environmental impact
 of chemicals by describing procedures followed during the development
 of a new product.  While many industrial chemicals were introduced
 into the marketplace before environmental testing became part of
 product development, the principles and laboratory test methods dej-_
 scribed can be applied to them equally well.  My message is That the
 impact of a chemical on the environment  can be predicted from the
 results of suitable laboratory tests.  The testing program,  coupled
 with appropriate use of chemicals, is our most powerful tool for envi-
 ronmental protection.   The function of additional early warning systems
 should be  to back up and plug the gaps in the predictive testing program.

       The development  process for a new chemical usually goes through
 four distinct stages.  The first is the inventive or conceptual stage in
 which the  compound is synthesized and partially characterized.  The
 chemical formula molecular structure and a few basic properties are
 determined.  Depending on a variety of factors beyond the scope of
 this discussion, the chemical may or may not be further developed as
 a useful product.

      In Stage Two a new compound is further characterized and general
 use categories are defined*  During this period we begin the evaluation
 of the  environmental impact of the chemical.  We  have found four key
 parameters are helpful  in evaluating that impact,  namely, stability,
 movement, bioconcentration and toxicity.
                              Stability
      The stability of a molecule under conditions encountered in nature
has a direct bearing on its impact on the biosphere.  The measurement
of thermodynamic properties related to stability using classical

                                   168

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techniques, for example, calorimetry, differential thermal analysis,
along with flash points and flammability limits are helpful in assessing
handling hazards.  However, for the assessment of environmental
impact it is more important to answer the question, is there a mech-
anism by which the chemical will be removed from the environment
under natural conditions?  Once the route  or routes for removal are
established,  measurements relating to the rate of decomposition are
made, and this data coupled with other information described below,
leads to  an estimate of lifetime and steady state concentrations in the
environment.

      Pertinent laboratory measurements  are the rates of hydrolysis
and oxidation of a molecule.  The results of such measurements can
be judiciously transferred directly to the environment.  Perhaps the
most important route of degradation of organic  chemicals in nature is
microbial metabolism.  The  classical measurement of oxygen uptake
by microorganisms as a result of their action on a test chemical is
relatively inexpensive, and provides useful data for estimating the
lifetime  of a molecule in aquatic  or soil environments.  If a molecule
degrades rapidly to materials already in the environmental sink as
indicated by these basic tests of hydrolysis, oxidation and microbial
decay, the probability of long-term problems arising as a result of
its use is greatly diminished.  Of course,  if the degradation generates
other compounds equally foreign  to the biosphere,  it is necessary to
evaluate the environmental impact of those compounds as well.
                             Movement
      The second key parameter for evaluation is movement.  Movement
encompasses release to the environment and the various pathways
followed after release.  If a molecule moves widely, its potential for
having an adverse effect may be  greatly enhanced.  Conversely,  rapid
dispersion in the environment often results in dilution to levels of no
practical concern.  Once  the chemical enters the environment, a
knowledge of its vapor pressure  and water solubility provide a basis
for estimating transport within the biosphere. For example,  if a
molecule is volatile,  stable, and relatively non-polar it will enter the
atmosphere and movement will be rapid and widespread.  Polar  mole-
cules tend to be more water  soluble,  and are more likely to move with
water.  This information is vital when considering which degradation
routes will be most important.   These measurements are simple to
make in the laboratory  but translation of the results to  a quantitative
prediction of movement in the environment is  difficult.   Comparison


                                 169

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 of laboratory data on test chemicals with that obtained on compounds
 whose movement in the environment has been at least partially deter-
 mined is of value in making predictions.
                            Bioconcentration
       In addition to movement with air, water and soil, a compound
 may enter living organisms and move throughout the complicated web
 of biological life.  It is,  therefore,  necessary to analyze the third
 area for concern; namely, bioconcentration.  Laboratory methods for
 measuring bioconcentration or predicting its likelihood have been used
 widely only in very recent years.   The bioconcentration mechanism
 believed to be operative for organic compounds is the preferential
 solubility  of the material in fat as compared to water.  Since the fat
 phase of the biosphere is  largely present in biological tissue, materials
 with high fat solubility and low water solubility are likely to undergo
 bioconcentration.  Thus,  a good qualitative indication of bioconcentra-
 tion potential may be obtained simply by comparison of the  solubility
 of a compound in water with that in non-polar organic solvents. For
 a more quantitative assessment, the partition coefficient, arbitrarily
 defined as the amount of a chemical dissolved in octanol divided by
 the amount dissolved in water in a system containing the chemical in
 equilibrium with the two phases, is usually taken as a good  indicator
 of bioconcentration potential.  The partition coefficient can  be  measured
 or calculated using the method of  Leo,  Hansch and Elkins. '•*•'  Recently,
 experiments by Neely, Branson and Blau^' show that a good correlation
 exists between measured  or calculated partition coefficients and the
 observed bioconcentration of non-metabolized chemicals in  rainbow
 trout.  It appears the bioconcentration potential of a chemical in the
 environment can be predicted with reasonable accuracy if its partition
 coefficient, movement,  and stability are known.
                                Toxicity
       The fourth key parameter that must be evaluated is toxicity or
more  broadly speaking, biological activity.  The initial toxicological
testing of .Dow products is done in-house using a series of relatively
inexpensive range finding tests.  These include evaluation of toxicity
to plants, microorganisms,  aquatic organisms, birds and insects.
(1) A. Leo, C. Hansch, and D. Elkins. Chem. Rev., 71," 525(1971).
(2) W. Neely, D. Branson, and G. Blau, to be published.

                                   170

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Testing on mammalian species includes~administration via ingestion,
inhalation, skin and eyes.   The testing is not extensive at this stage
and is designed to determine the  effects of acute exposure only.  How-
ever, when coupled with the information described earlier in terms of
bioconcentration,  stability, and movement, and also with some knowl-
edge of the effects  of chemicals with similar^ properties onTiving
organisms, a pretty good indication can be  obtained of the overall bio-
logical effects of the chemical.

      Thus, at this stage of development the environmental impact of
a chemical can be assessed with some degree of certainty.  The basic
measurements have been vapor pressure,  solubility in water and or-
ganic solvents, partition coefficient (calculated or measured),  biological
oxygen demand, reactivity with water and oxygen, and acute toxicolog-
ical range finding tests.

      It might be useful to consider an example.  Table 1 shows the
data that would be obtained in Stage 2 on three chemicals with widely
differing properties.  Based on this information one might predict the
following:  Perchloroethylene would tend to move mostly in the atmos-
phere and would have only a very slight tendency to bioconcentrate.
The preliminary data indicates a need to further investigate the
persistence of perchloroethylene as commercial development proceeds.
Hexachlorobenzene appears to be stable and would tend to bioconcen-
trate.  Without doing further work, we would predict it could be a
problem if released broadly to the environment in large quantities.
Propylene glycol would tend to move with water and be rapidly biode-
graded.  No environmental problems are anticipated with its use unless
a massive release  at one location occurs.

      A significant comment may be offered at this point.  Environmental
impact should always be judged on the basis of the combination of all
four key parameters,  i.e., stability, movement, bioconcentration and
toxicological activity.   They are strongly interrelated.   For example,
it is possible  for a material to be stable and persist for  a long time,
but if it is something like concrete or glass and remains confined or
has very low toxicity,  it is not likely to constitute an environmental
problem. Another example relates to bioconcentration.   It is  often
assumed that  if a compound has  a high potential for  bioconcentration
it automatically has the potential for severe environmental damage.
However, bioconcentration is not likely to be a problem if the  molecule
is unstable and has a low environmental lifetime. Bioconcentration is
a reversible process,  and as long as ambient levels are low because
decomposition is fairly rapid, build-up in living tissue is not likely to
be significant.

                                 171

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             TABLE 1.  STAGE TWO EVALUATION OF ENVIRONMENTAL PROPERTIES
Vapor Pressure,
 mm Hg at 20 C
Water Sol.
 ppm at 25 C
Partition Coefficient
 Calculated, Log
Bioconcentration Factor
 in Trout(a)
BODg, % of theoretical
Reactivity
 Water
 Oxygen
Acute Toxicity
                         Perchloroethylene

                              13

                             150


                               2.26

                              40
                              Slow
                              Slow
                              Low
Hexachlorobenzene
    10-5
  .035


 6.3

 8.500


 0


Stable
Stable
Low
                Propylene
                Glycol
                0.2
                    00
                    -0.8
                     70

                    Stable
                    Stable
                    Low
 (a) W. Neely, D. Branson, and G. Blau, to be published.
      •
       Stage Three of product development is often called the pilot plant
 stage.  It usually involves manufacture of the material in developmental
 quantities, providing necessary information from which to design a
 production plant.   In addition,  the  proposed application of the material
 is usually fairly well defined and serious efficacy testing is undertaken.
 Environmental impact is also evaluated in more depth during this
 period of development. The testing required depends  on the intended
 use of the chemical and the results of the environmental impact assess-
 ment made during Stage Two.  For example,  in terms of stability,
 if it has been observed that a molecule would be readily degraded by
 action of microorganisms or through reaction with water or oxygen,
 and the molecule is water soluble and likely to migrate to the water
 phase in the  environment,  ambient levels of the chemical will remain
 low precluding widespread environmental problems. ^Very little addi-
 tional information would be needed in the evaluation of stability during
 Stage Three.  However, if no route for exit from the environment is
 apparent,  more detailed studies maybe  necessary.  Possibilities
 include evaluation of photochemical decomposition or studies on
 metabolism by plants and  animals.

      Environmental movement may be further  evaluated by measure-
ment of adsorption on solids, migration in  soil  and the transport
across the water/air interface.  Movement in a closed laboratory
                                   172

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ecosystem may also be observed.  These techniques have been used
in the study of pesticides, but their use has not been extensive for
industrial chemicals.

      Additional toxicity testing may also be required at this stage.
The type of studies necessary depends on an evaluation of the extent of
exposure of various types of biological life to the chemical and the
results of the earlier toxicity testing.  At this point sufficient mamma-
lian toxicological testing would be conducted to set maximum allowable
exposure levels for humans who must  handle the chemical during pro-
duction, transportation and use.  While many factors influence the
design of a toxicological testing program,  one important guideline for
applying the results is that the exposure levels,  route of entry,  and
test species used be appropriate for the type of hazard being evaluated.
Depending on the physical and chemical properties of the  compound and
the extent of human exposure anticipated, costs for mammalian toxi-
cological testing may run from several thousand to several hundred
thousand dollars per product.

      An effective medical surveillance program for the  experienced
engineers and scientists handling the chemical at the  pilot plant stage
provides real life experience on  safe handling procedures.  Analytical
methods are also perfected at this  time to allow detection of the chemical
in question in environmental samples.

      Let's go back to our three  examples.  An investigation of the
photodegradation of perchloroethylene showed it to degrade in sunlight
with a halflife of the order of two days.  Since it would be expected to
move in the atmosphere, photode composition would be expected to  be
the most significant route of exit of perchloroethylene from the environ-
ment.   The rate is fast enough so that problems from environmental
buildup would not be anticipated. Sufficient mammalian  toxicological
work has been done to establish a TLV of 100 ppm for the vapor provid-
ing a criterion for safe handling  of the chemical by humans.  In the
case of hexachlorobenzene additional work has been done to show it
has a high chronic mammalian toxicity.   This, together  with its sta-
bility and likelihood for bioconcentration,  suggests HCB should not be
developed for applications where it would be  spread broadly in signif-
icant quantities in the environment.  Propylene glycol has had a con-
siderable amount of additional toxicological investigation primarily
to allow its use in food, but the early basic studies had shown it would
not persist or bioconcentrate,  and therefore,  would not  likely cause
adverse environmental effects.
                                  173

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       Stage Four might be characterized as early commercialization of
 the new product.  During this stage production of commercial quantities
 of the compound is begun.  Since the production plant itself is a potential
 source of discharge of the material to the environment, observations
 on the environment surrounding the production plant provide a pretty
 good indication if the initial test data correctly predicted environmental
 impact.  Good industrial hygiene and medical  surveillance programs
 for employees in the production plant give an early -warning if potential
 problems exist that had not been anticipated from mammalian toxicolog-
 ical data and pilot plant operations.

       Thus, the evaluation of the environmental impact and safe handling
 of a chemical by humans  involves not only predictive testing in the
 laboratory carried along at various, stages of the development, but also
 careful  observation on the actual environmental impact associated with
 its manufacture and handling at the production site.

       An additional point  might be  made, particularly with respect to
 chemicals already in commerce.   Laboratory data of the type described
 earlier, together with appropriate environmental parameters, may be
 used to  calculate the rate constant for removal of the chemical from
 various parts of the environment.  If one can estimate the  rate of input
 of the chemical, and if steady state conditions are assumed,  the con-
 centration of the chemical in that part of the environment can be calcu-
 lated.  Comparison of the expected steady state concentration with the
 appropriate toxicity threshold gives an estimate of the margin of safety
 associated with that rate  of input of the chemical.  A few measurements
 of ambient levels serve to indicate if steady state conditions have been
 reached or if environmental buildup is still occurring. I think this type
 of analysis is  of value, especially in the context of early warning sys-
 tems for environmental monitoring.

      As I indicated earlier, this presentation has been structured
 within the  framework of product development.  It also reflects the
 approach and point of view of at least one major chemical company.
 Programs similar to this one  are the primary device to protect  both
 humans and the environment in general from adverse effects  caused
 by environmental exposure to  products of high technology.  I believe
 such programs are effective.  However, no program is perfect and
they all suffer from dependency on human judgment and understanding.
 Therefore, the development and incorporation of additional practical,
meaningful Early Warning Systems into our society that can supplement
existing protective programs without inhibiting innovation is certainly
a worthy objective.
                                  174

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          ENVIRONMENTAL STRESSOR MATRIX SYSTEM
                       FOR EARLY WARNING

                         David L. Morrison

                            BATTELLE
                       Columbus Laboratories
                           Columbus, Ohio
                          INTRODUCTION
      Early identification of toxic substances continues to be a press-
ing problem facing mankind.  Despite diligence on the part of industry
and' government,  toxicants are introduced into  man's environment
from a variety of sources.  The need for an early warning system
has been well established in the previous papers presented at this
conference.  It is clear that any early warning system must consist
of several interconnected elements — Surveillance leading to hazard
identification:  Continuous surveillance of toxicants  within commerce,
other warning centers (e.g.,  poison control),  scientific literature
especially toxicology, and technical meetings.   Assessment of the
nature and severity of the hazard:  Qualitative  linking of potential
cause and effect relationships by recognized toxicologists, and
quantitative modeling efforts to estimate magnitude  of problem and
select best control options. Action by decision makers:  Agency or
agencies to select and control actions.

      Through two pripr studies^ ^) for ^e Department of Health,
Education, and Welfare,  Battelle has examined the  subject of early
warning systems and has developed a concept for a  system.  The
system deals with environmental stressors which are defined as the
environmental agents or factors of concern reduced to their simplest
terms or their most fundamental unit.  Examples of environmental
stressors and hierarchical patterns are presented in Table 1.  Under
a current contract for the Office of Toxic Substances of the Environ-
mental Protection Agency,  Battelle is further  studying and evaluating
methods for toxic substance identification.  The results of the current
study were dicussed earlier in the session  by  T.  J.  Thomas and
J. E. Flinn.   This paper is addressed to the use of of an environ-
mental stressor matrix as  an early warning concept which was evolved
during the previous studies.
                                 175

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           TABLE  1.  EXAMPLES OF ENVIRONMENTAL STRESSORS



 CHEMICAL

      Organic Compounds

          Ke tones

               Methylbutyl ketone
               Methylisobutyl ketone

          Aromatic compounds

               Polychlorinated biphenyls

      Silicon, Germanium, Tin, Lead, and Compounds

          Halides of Ge, Sn, Pb
          Oxides of Ge, Sn, Pb

      Pesticides

          DDT  (including its isomers and dehydrochlorination
               products)
          2,4,5-T

 BIOLOGICAL

      Allergens


          Inhalants
          Foods

      Infectious Microorganisms

          Bacteria

               Salmonella
               Viruses

PHYSICAL

     Noise

     Radiation
                                176

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           SURVEILLANCE - HAZARD IDENTIFICATION
      The major categories of information needs of an early warning
system have been identified as(3):
                                 r
      (1)  Primary production data
          (a) Description of processes
          (b) Number and location of plants
          (c) Annual production records
          (d) Distribution and use categories

      (2)  Secondary product formulation
          (a) Description of processes
          
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 concepts embodied in surveillance of commercial trends with toxi-
 cological responses.  If quantitative information can be obtained,
 the stressor matrix can provide much of the needed information for
 mathematical modeling.

       The environmental stressor matrix concept is illustrated in
 Figure I.  The breakdown of the classifications under each of the
 columns of the  matrix is listed in Table 2.  Each row in the matrix



St reiser







Sourco
Quantity per
unit time
or
Quantity per
unit activity



TRANSPORT PATH


Medium
Concentrator







H
U
Kf
A
N
B
I
O
T
A


Compartment
Expoiure per
unit time


Compartment
Expoiure per
unit time


Portal of
'Entry
Quantity per
unit activity



Target (Site)
of Action
Concentration
per unit
exposure


Target of Action
Concentration per unit
exposure

Population
Subgroup
Modifier!



Croup
Modifier
Factor




Consequence!



Consequence!


      FIGURE 1.
PRELIMINARY ENVIRONMENTAL STRESSOR
MATRIX CONCEPT
is headed by an environmental stressor (Table 1).  In the second
column, sources  (the amount of the stressor released to the environ-
ment from a given source) are tabulated.  Convenient units for the
information in this column could be quantity (mass, number,  decibels,
etc.) per unit time or quantity per unit activity in the economic
sense.  The  third column of the matrix, medium, represents an
instantaneous distribution of the stressor among the  media indicated.
The values in this column could be  expressed in  terms of amount
per unit volume, area,  or mass appropriate to the stressor.   There
should be a mass  balance between all of the second and third columns.
At this point,  it appears convenient to separate the stressor matrix
                                 178

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                           TABLE 2.   BREAKDOWN OF COLUMN CLASSIFICATIONS
  Use standard Industrial classlfl-
  cations.  Major divisions glvsn
  below.

  - Agriculture, Forestry, snd
    Fisheries
  - Mining
  - Contract Construction
  - Manufacturing
  - Transportation, Communication,
    Electric, Gas, and Sanitary
    Services
  - Wholesale end Retail Trade
  - Finance, Insurance, and Real
    Estste Services

Medium

  Atmosphere
  Hydrosphere
  Lithosphere
  Biota
  Humans
Compartment - Humans

  Domestic
  Occupational
  Service
  Recreational
  Trans porta tlona1

Portal ot Entry

  Skin
  Respiratory tract
  Alimentary tract
  Genlto-urlniry traet
  Sensory spparatus

Target (Site) ot Action

  Total organism
  Systems
  Organs
  Tissues
  Cells
  - Chromosomes
  - Organelles
  - Membranes

Population Subgroup
  Modifiers  - Humans

  Genetic
  Group patterns
  Individual experience
  Physiological status

Consequences - Humans

  Physiological-psychological
  Longevity
  Productivity
  Metabolism
  - Reproduction
 • • Normality
  Economic
  Political
  Sociological
Compartment » Biota

  Producers
  Herbivores
  Carnivores
  Detrltivores

Targets of Action - Biota

  Biome
  Ecosystem
  Community
  Population
  Organism

Croup Modifier  - Biota

Consequences  -  Biota

  Longevity
  Productivity
  Reproduction
  Norms1Ity
                                                  179

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 into two parts, one dealing with humans and the other treating the
 biota.  In the next column in the humans section of the matrix,
 compartment,  the exposure to the stressor per unit time (and,  if
 convenient, unit concentration) is tabulated.  This  column effectively
 partitions the exposure according to individual activities.  Under
 the portal of entry column, data on the stressor are tabulated,  by
 amounts,  in the various pathways.  The target site of action is
 identified,  and the concentration of the stressor in the target for a
 given unit of exposure is tabulated.  Population subgroup modifiers
 are factors that should be applied against sensitive population sub-
 groups.  The amplification factor and the sensitive group must be
 tabulated.  Under the consequences column,  the effects or conse-
 quences of exposure  to a given stressor are presented.  In the  biota
 section of the matrix, it appears desirable to have different Column
 headings, perhaps amount accumulated per unit mass, within the
 classifications of producers,  consumers,  and detritus.  The target
 for the  impact of the stressor are the biome,  ecosystem, community,
 population,  or organism; and if there are modifiers,  they should be
 noted.

       The environmental stressor matrix provides a  framework for
 following the stressor through the environment, and the quantitative
 data will serve as input to predictive mathematical models.  By
 inspection of the matrix, the  significant sources of the stressor and
 principal elements along its transport path can be identified.  This
 information in itself  is useful to suggest means to minimize or
 eliminate the consequences of a stressor  in the environment.  If
 attention is directed  to one of the columns of the matrix,  the possi-
 bilities  for synergistic or antagonistic effects exists.  Data should
 be evaluated in light  of these possibilities.

       Each column of the matrix provides  a means for hazard identifi-
 cation.  For example, the first column,  sources,  relates directly
 to die first of three information needs noted previously.  A detailed
 examination of primary production data,  secondary product formula-
 tion, and end-product distribution and use can serve  to identify if
 there is a loss of the product to the environment.

       For example, in the study of the environmental hazards  of
 mercury'*', an examination of the use pattern for 1965 indicated how
 mercury was added to the environment.  The electrolytic preparation
 of chlorine and caustic soda had required large quantities of mercury.
 It was estimated that, by 1970,  about 16, 000 flasks*  would be  consumed
•A flask - 76 pounds.

                                 180

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annually in the electrolytic production of chlorine.  This amounts to
about 44 flasks (3, 300 Ib) per day,  and could be a source of contami-
nation for water and for air.  Agriculture, including  its use of
fungicides, herbicides, and insecticides,  added about 250, 000 Ib of
mercury to soil,  water, and the air.  About 575, 000  Ib of phenyl
mercurials, mildew-proofing materials for paints, found their way
into the air, streams, and the soil. Antifouling  agents in paints
accounted for  about 20, 000 Ib of mercury in the air,  streams,  and
soil.  Through the use of phenyl mercurials by the paper industry,
about 45, 000 Ib per year of mercury were added to the waters.
Through the burning of paper, some of this entered the atmosphere.
The use of approximately 250, 000 Ib of mercury in pharmaceuticals,
especially as diuretics and anti-infectives, led to direct contamina-
tion of man with mercury and subsequent addition to  waters and the
atmosphere.   The preparation of catalysts required approximately
75, 000  Ib of mercury that found their way into air, water,  and
probably soil.  Likewise, amalgamation led to about 37, 000 Ib  of
mercury for release to soils and waters.  About 125, 000 Ib of
mercury were used in dental preparations. Some of this probably
became an environmental hazard.

      To illustrate further the applicability of the environmental
stressor matrix concept, the available data for the lead(?)  and
pesticide(°) case studies were summarized and are presented in
matrix  form in Table 3.  Only a single line entry for the source
information was made for each of the stressors, and the quantity of
the stressor produced annually is indicated by the parenthesis. A
more complete representation of the source information would be a
two-dimensional array showing  the transfers  of  the stressors  between
industries.  For illustrative purposes, only a few categories under
the transport paths are shown and  the data are limited to humans.

      An examination of the use pattern for 1969 and the immediate
years preceding indicates how lead is added to the environment.
Although there have been fluctuations in quantities in the use cate-
gories reported, no major changes in the categories themselves have
been reported during the last decade.  That is, the major uses of
lead during 1969 continued to be (in decreasing order) in the produc-
tion of storage batteries and accessories, gasoline antiknock additives
(mostly tetraethyllead), red lead and litharge pigments,  ammunition,
solder, cable covering, and calking lead.  An inspection of the ma-
terials  requirements and manufacturing processes for the lead-acid
storage batteries,  e.g.,  preparation of pasted plates, preparation
and assembly of grids, and particle size distribution and grinding  of
                                 181

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TABLE 3 . ENVIRONMENTAL STREJSOR MATRIX - PRELIMINARY
Source (Standard Industrial Classification)
•Construction,
Agricultural Metal Special Trade
Production Forestry Mining Contractors
Stressor 01 07 10 17

Lead (501,886)<*> 112.256
DDT 16.770 3.747

00
to
' Medium
Air. Water, Land. Domestic,
yg/m3 U8/1 UK/8 V$i/m
' Lead 1.6 to 4.0 1.5 to 60.0 13. 9 to 95. 7(0
(urban)(e) (drinklng)(0
0. 5 (composite
rural U.S. )(g)
Otdnance Primary Fabricated
and Chemicals and Metal Metal Electrical
Accessories Allied Products Industries Products Machinery
19 28 33 34 30
Tons
'<7.805 373.014 (1. 539, 757)(b< c) 211,681 568,121
<67.897*d>
\
Compartment Portal of Entry
Respiratory Alimentary
Occupational. Transportational, Skin, Tract, Tract.
UK/m3 uR/m3 ug/day PR/day Wg/day
1. 0 - 49. fl(e> 0. 1 - 3. 5 Negligible 20. 0<0 300. fXO
(alkyl lead)(fi)
1.0 -11.0<") 1.3 -2.8
DDT     IxlO"4 (total     0.02 (drinking)
          U.S. average)
                 0.0005
                             (Insecticides)
0.01 -0.04
40.0

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                                                                            TABLE 3 . (Continued)
oo
                                         Target (Site of Action)
         Lead
System.
pg/100 g
mood 17
         DDT
      tissues
 (Autopsy Tissue). &)
     ug/100 a
 Bone (flat) 210-1110
 Bone (long) 670.3600
 Liver 120
 Kidney 50
 Muscle 80
 Spleen 30
 Lung 20
                                                              Ash
                                                     Adrenal S3
                                                     Aorta 160
                                                     Cecum 38
                                                     Kidney 120
                                                     Larynx 95
                                   Liver 150
                                   Lungs 67
                                   Pancreas 69
                                   Trachea 58
Body Fat
2.4 - 3.7 ppmf
                                                                                                                         Consequences
                                                                                                   Acute
TEL penetration of skin:
  Insomnia, headache,  rest-
  lessness, dizziness.
  irritability,  ataxia. delu-
  sions, anemia, and some-
  times convulsions

Ingestion of metabolic lead:
  Pain, leg cramps,  muscle
  weakness, paresthesias.
  depression, coma, death
                                                           Mild cases
                                                             Headaches, dizziness.
                                                             gastrointestinal disturbances,
                                                             numbness,  and weakness of
                                                             extremities, apprehension,
                                                             and hyperirritability
                                                           Urge doses
                                                             Muscular tremors,  convulsions.
                                                             cardiac or  respiratory failure,
                                                             and death
                                                        Chronic
                                                                                                                                    Anorexia,  a metallic taste/ constipa-
                                                                                                                                     tion and severe abdominal cramps.
                                                                                                                                     pallor, elevated blood pressure.
                                                                                                                                     wrist drop, foot drop.
                                                                                                                                     encephaloparhy
       (a) Mine production of recoverable lead In 1969.
       (b) Total new supply of U. S. lead in 1969.                                                                           '                   '
       (c) Total consumption based on SIC categories; estimated undistributed consumption 43.300 tons.  1969 use consumption pattern gives 42.000 tons undistributed consumptlor
           (Mineral Industry Surveys.  Lead Industry - Preliminary Totals for 1970, U. S. Department of Interior, Bureau of Mines.)
       (d) Frear. D.E.H.. "Pesticide Handbook-Entoma".  Twenty-First Edition (1969). p 28 (Pesticide Usage, 1964).
       (e) Symposium on Environmental Lead Contamination, December 13-15,  1965,  PHS I ublication No. 1440 (March, 1966).
       (0  Haley, T. J., Air Quality Monograph No.  69-7, American Petroleum Institute. N.  Y.  (1969).
       (g) U. S. Public  Health Service.  Survey of Lead in  the Atmosphere of Three Urban Cc.mmuntties.  Publication No. 999-AP-12 (January. 1965).
       (h) Hayes, W. J., "Monitoring Food and People for Pesticide Control", In Scientific Aspects of Pest Control.  Publication 1402, National Academy of Sciences - National
           Research Council, Washington.  D.  C. (1966).

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lead oxides revealed cases of lead intoxication in 66 battery-based
industries in Pennsylvania.   The use of old battery cases for fuel
and resulting lead-containing ash also were identified as environ-
mental hazards of air and soil.

      Examination of the use pattern of leaded gasoline additives
tetraethyllead (TEL) and lesser amounts of tetramethyllead (TML)
indicated that leaded fuels continue to be a major source of environ-
mental lead.  Each gallon of today's gasoline contains on the average
of 2 to  3 grams of lead (maximum of 4 grams),  which adds up to
approximately 540 million pounds of lead consumed,  according to
gasoline sales.  An estimated two-thirds of the lead exits  through
the exhaust,  and about half of the exhausted lead becomes  airborne,
that is, each year about 180 million pounds of lead swirls  into the
atmosphere.  Analysis of atmospheric precipitation samples of
lead and other metals collected by a nationwide network of 32 stations
throughout the United States  indicated that the concentration of lead
in precipitation correlated with the amount of gasoline consumed in
the area in which the sample was collected.   The above  two investi-
gations suggest that leaded gasolines contribute notably  to the
environmental (soil and water) burden.  Red lead and litharge-based
paints were identified as an environmental hazard during shipscrapping
because of the high temperatures involved in burning off (volatilizing)
the spent paint.
                   ASSESSMENT - VERIFICATION
                 Qualitative-Pollution Chain Diagrams
      Once a potential environmental hazard is identified, it is impor-
tant to determine the nature and extent of the hazard and to verify
that cause and effect relationships exist. A pollution chain diagram
which graphically presents the environmental flow of the stressor
from its sources to its receptors is useful.  Examples of pollution
chain diagrams for lead and DDT are shown in Figures 2 and 3.
These diagrams can be used for a qualitative assessment of potential
hazard or  can  be used as the basis  of a mathematical or quantitative
evaluation.

      For  example, there is little indication of lead accumulation in
foods, and the  concentration of lead in drinking water is relatively


                                 184

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                                             Neighborhood environment I
                                                 Lead mining,
                                               smelting, refining
FIGURE 2.  POLLUTION CHAIN DIAGRAM FOR THE

             ENVIRONMENTAL STRESS OR LEAD
                           185

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                  Removal from
                   environment
FIGURE  3.   CRITICAL PATHS OF DDT IN

              THE ENVIRONMENT
                       186

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Code          Component OP Process Description
   1       DDT used in U. S. in 1964
   2       DDT used in Forestry in 1964
   3       DDT used in Agriculture in 1964
   4       DDT used in Urban area in 1964
   5       Amount of DDT in atmosphere over U. S.
           at one time
   6       Half life (Tl/2) of DDT in atmosphere
   7       Deposition rate of DDT in atmosphere
           (1964)
   8       Inhalation of DDT from atmosphere
           (a) In heavily sprayed areas
           (b) In large cities
   9       Deposition rate of DDT in atmosphere (1964)
  10       DDT applied to soil system in 1964'
  11       Rate of injection  of DDT in atmosphere over
           U. S. (1964)
  12       Tl/2 of DDT in Soil System
  13       Annual DDT in runoff
  14       DDT in ground water
  15       Amount of DDT that reached estuaries and
           ocean from U. S. in 1964
  16       DDT intake from drinking water
  17       Degradation of DDT aerbic water
  18       Total  DDT in foodstuffs
  19       DDT intake from food
  20       DDT metabolized by. general population
  21       DDT consumption general population
  22       DDT loss from body storage
     DDT Concentration,
      degradation rate
18.14 x 106 kg
3.40 x 10° kg
9.53 x 106 kg
5. 22 x 106 kg
3.6x 105 g

30 days
3. 86 x 10-7 g/m2/year

0. 0002 to 0. 0008 mg/man/day
0. 000009 mg/man/day
3. 86 x 10-7 g/m2/year
12.93 x 10° kg
3.0 x 106 g/year

3. 0 years
2. 86 x 105 kg
Insignificant
2. 63 x 104 kg/yr

0.000023 mg/man/day
Tl/2 = 5. Ox 10-2
Data unavailable
0.04 mg/man/day
Data unavailable
0.09 mg/man/day
 <0.3%/day
                                           187

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 low.  By inference, then, the primary ingestion path for lead is
 through pica with the source being lead paints.  The effect — the
 observation of high lead levels in children from urban substandard
 housing areas — can readily be related  to one major cause.  Since
 the use of lead as a pigment for indoor  paints has been banned,  the
 environmental hazard is  localized.   The obvious  corrective action
 is to locate and remove lead-based paints from ghetto houses.

      Similarly, cause and effect relationships can be discerned for
 the potential human hazards from DDT  in the environment.   Two major
 pathways were considered.  Figures:3 and 4 summarize the observa-
 tions.  The first, the direct pathway, deals with the direct uptake
 from primary sources of pesticide  release.  Primary sources were
 manufacture and application.  Human exposure was by inhalation.
 Dermal uptake and ingestion are secondary features.  Accidental
 poisonings remained about the same, even though the frequency of
 application and the acute toxicity of the new pesticides has increased.
 These trends suggest that a very credible job of education is being
 done at the industrial level.  Since  most of the victims of death from
 accidental poisoning were children,  further reductions could be made
 by reduction of the total toxicant contents of the home package* to
 below the child lethal dose,  where possible,  and elimination of those
 chemicals that cannot be used within the safety margin (e.g., sub-
 stitution  of carbamates and  pyrethrians for organophosphate insecti-
 cides).  Prescription and dispensing pesiticides by trained profes-
 sionals would also reduce accidental deaths.  Aerial application
 accounts for the largest number of  deaths and either elimination or
 control of this method  appears worth study.

      The second pathway, the indirect pathway,  involves human
 exposure by translocation through the air,  water, or food.  While
 more complicated to consider and model, the indirect pathway in-
 volves the total biosphere.  The general population of the United
 States is  exposed by this means. Serious conflicts exist in the  data
 as to which indirect pathway Leads to the major store of pesticides
 in man.   On a worldwide basis,  the persistent pesticide content of
 man is remarkably constant.  Within the United States there are,
 however, significant racial  and geographic differences.  Such differ-
 ences are difficult to explain if food is the  major transport pathway
 to man.   The  southern population and the southern Negro have greater
 levels of pesticides  than the northern equivalent populations.  On
the basis of this,  together with some indirect evidence from residues
in animals, it is likely that only 50  percent of the body burden is from
food;  the remainder may come from inhalation of insecticide aerosols
                                 188

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or dust laden with insecticides. If these observations are
then control of the human burden of pesticides by control of food
residues, as is now practiced, is  at best only partially effective.
                 Quantitative - Mathematical Models
      The environmental stressor matrix provides a means to sum-
marize pertinent data for a quantitative assessment of the magnitude
of an environmental problem.  In its most general sense,  the inte-
grated exposure to man from an environmental stressor can be
represented as:
               E...  = /   S..  (t) P., (t) D. (t) dt,
                 inL-   I    jfc     jk     1      '
where E   is the exposure from stressor i over time t  to t  through
        IJK                           .               12
           pathway j to man at location k

        S., is the time  varying source strength of stressor i at

           location k,

        Pjk is the "pathway term" for pathway j and location k,  and

        D. is the exposure commitment rate for stressor i.

A stressor-environment-maja relationship has to be determined to
represent the chemical, physical,  and biological processes that are
elements  of the terms Sik, Pjk»  an(* Di-   The pollution chain diagram
can be used as the  basis for developing the quantitative relationships
involved.   A mathematical model was developed from the pollution
chain diagram for lead (Figure -2) to predict blood lead levels due to
the intake of lead by ingestion and inhalation.   The schematic repre-
sentation  of the model for lead in the body is shown in Figure 5.
Literature data on intercompartmental transfer coefficients (e.g.,
elimination rates) were used in the model and predicted blood lead
levels resulting from ingestion and exhalation were compared with
measured values.  The estimates from the mathematical model were
similar in magnitude to the measured blood lead levels.

      Several exercises were performed with model to determine the
nature of potential hazards and to estimate the effectiveness of
                                189

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        From spray applications
        From soil pool
                                    Food
                  Animal Products
                  640 Ib/rnon/year
           Meats
    Poultry
Dairy
Fat
and
oils
                                   Plant Products
                                   798 Ib/man/year
Fruits
vegetables
Grans
Others
                                 \>  NX
                                    Man
FIGURE 4.
CRITICAL PATHWAY FOR DDT TO MAN THROUGH THE
DIETARY PATTERNS OF THE GENERAL POPULATION
            t
    Total intake of meats and meat products was 157. 7 Ib/man/yr.
    Total intake of poultry was 87. 7  Ib/man/yr.
    Total intake of dairy products was  364 Ib/man/yr.
4.  Total intake of fats and oils was 51.3 Ib/man/yr.
5.  Total intake of fruits was 132. 1 Ib/man/yr.
6.  Total intake of vegetables was 199.9 Ib/man/yr.
7.  Total intake of grains was 35. 7  Ib/man/yr.
8.  DDT  intake attributed to meat and meat products was
    0.31  mg /man /day.
9.  DDT  intake attributed to plant products was 0. 04 mg/man/day.
                                   190

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                    Inhalation
Ingestion
                     Lung
                                 Blood *
                         I
| Total body
1 Urine 1

Bone

                                                   Kidneys
               \
                 FIGURE 5.  LEAD IN BODY MODEL

possible control  strategies. Figure 6 shows blood lead-level con-
centrations as  a  result of removing lead from the air.  The long-term
blood lead levels are controlled by the continuous daily ingestion
of lead in foods (300 mg Pb per day).  In the case of an individual
chronically ingesting more lead than the average intake, e.g., ingest-
ing 1000 mg of lead daily instead of 300 mg, and residing in a city
location where he is inhaling airborne lead at  a  concentration of
1.0 mg/m3, the blood lead concentration would rise to a new equili-
brium value of approximately 54 mg/100 g blood as shown in Figure 7.
Blood lead levels approaching 50 mg/100 g of blood warrant therapy
in order to avoid the central nervous system syndrome of adult or
pediatric plumbism.  Since a few small chips  of paint prior to the
lead pigment ban may contain 100 mg of lead,  control of lead ingestion
by a young child  having pica to an intake of less than 1000 mg/day is
obviously a difficult task.   A substantial improvement in the environ-
ment is  required.
                               ACTION .
      The previously described elements of the environmental stressor
 matrix system are passive elements,  i.e., they represent the
                                 191

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                  100       200       300      400       500      600
                      Time After Inhalation Source of Lead Becomes = 0, days   \
700
FIGURE 6.   BLOOD LEAD CONCENTRATIONS AS A RESULT OF REMOVING
              LEAD FROM AIR


              At time = 0,  blood lead level due to continuous daily ingcstion of
              300 /Jg Pb per day  and inhalation of airborne lead as indicated on

              each curve.
                                      192

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Ingestion of 1000 fig
Pb per day
                 300       400
                     Time, days
500
600
700
 FIGURE  7.   CHRONIC LEAD EXPOSURE

               Constant inhalation of 1 tig
               Pb/m3.
                     193

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identification and collection of data and information upon which subse-,
quent actions are to be taken.  The final element of any early warning
system must include several options for actions.  Potential environ-
mental hazards once they are identified must be drawn to the attention
of some decision maker.  The means to do this must be forceful and
direct enough to attract the decision maker's attention but must
not prematurely raise alarm among public sectors. Opportunities
must exist for corrective action to be taken by industry or other
sources without severe  economic or operational penalties.  A detailed
discussion of action systems are beyond the  scope  of this paper.  It
is essential,  however, that such systems must include a multiplicity
of disciplines to provide an evaluation of the potential hazards, and
government  as well as industrial decision makers to affect the
required actions.  The two elements of the environmental stressor
matrix system,  surveillance and assessment described previously,
can  be adapted to fit the  needs of any action system.
                            REFERENCES
(1)  Lutz, G. A., Gross, S. B., Boatman, J. B., Moore, P. J.,
     Darby, R.  L.,  Veazie, W.  H., and Butrico,  F. A., "Design of
     an Overview System for Evaluating the Public-Health Hazards
     of Chemicals in the Environment.  Volume I.  Test Case Studies.
     Volume II.   The Overview System", Final Report from Battelle
     Memorial Institute,  Columbus Laboratories,  to the United States
     Public Health Service (July, 1967).

(2)  Morrison,  D. L., Menzel,  D. B., Nielsen, K. L.,  Levin,  A. A.,
     Hamilton, C. W., Raines,  G.  E., and Bloom,  S. C.,  "Technical,
     Intelligence, and Project Information System for the Environ-
     mental Health Service.  Volume I. Management Assistance and
     Planning",  Final Report from Battelle Memorial Institute,
     Columbus and Pacific Northwest Laboratories, to the U. S. De-
     partment of Health, Education, and Welfare,  Environmental
     Health Service (June 29, 1970).

(3)  Butrico,  F. A., "Early Warning Systems Concerned with En-
     vironmental Contaminants", Am.  J. Publ. Health, j>9  (3),
     422-447 (1969).
(4)  Lee,  D.H.K., Private communication, Division of Environmental
     Health Services, National Environmental Health Services  Center
     (1969).
                                194

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(5)  Isard, Walter, "Some Notes on the Linkage of the Ecologic and
    Economic Systems",  Regional Science Association Papers,
    Volume XXII, 1969 European Congress, Budapest (1968).
(6)  Hutchison, B. R.,  and Krause, E. A., "Systems Analysis and
    Mental Health Services", Community Mental Health Journal,  J3 (1),
    29 (1969).
(7)  Lutz,  G. A., Levin,  A. A., Bloom,  S. G.,  Nielsen,  K. J.,
    Cross, J.  L.,  and Morrison, D. L., "Technical, Intelligence,
    and Project Information System for the Environmental Health
    Service.  Volume III.  Lead Model Case Study",  Final Report
    from Battelle Memorial Institute, Columbus Laboratories, to
    U. S.  Department of Health, Education, and Welfare, Environ-
    mental Health Service (June 29,  1970).
(8)  Yoss, J. K., Blaylock,  J.  W., Schneider, M. J., Schwendiman,
    L. C., Touhill, C. J.,  Jr.,  Templeton,  W. L., Wildung, R. E.,
    and Menzel,  D. B., "Technical,  Intelligence,  and Project Infor-
    mation System for  the Environmental Health Service. Volume IV.
    Pesticides Model Case Study", Final Report from Battelle
    Memorial Institute, Columbus and Pacific Northwest Laboratories,
    to U. S. Department of Health, Education, and Welfare, Environ-
    mental Health Service (June 29,  1970).
                                195

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                  PUBLIC INTEREST METHODS FOR
                  ASSESSING CHEMICAL, HAZARDS

                       Albert!. Fritsch, Ph.D.
                Center for Science in the Public Interest
                          Washington, D. C.
                           INTRODUCTION
      We have evolved an early warning system for detecting and
 assessing chemical hazards.  While our resources are limited, our
 numbers small and our methodology simple,  still we are determined
 to continue to show proper scientific concern about the vast explosion
 of chemicals inundating our society.  We have never taken the time
 to totally evaluate the success of our efforts, but CSPI has kept in
 constant touch with the mass media and we have goaded regulatory
 agencies into taking many of our projects  seriously.
                        GENERAL REMARKS
      While speaking mainly of CSPI activities I must admit that
there is a strong and growing current of cooperation among a number
of public interest,  community,  environmental, consumer and labor
groups.   We're all limited in resources and so such cooperation is
necessary. Thus environmental legal groups  such as Environmental
Defense Fund and Natural Resources Defense  Council work with us
on asbestos and gasoline additive problems.  We work with Con-
sumer's Union on Aerosols, with Concern Inc. on lead problems,
with Health Research Group on talcs,  and with the Urban Environ-
ment Conference on air pollution problems. Actually in the course
of a year we join forces with 30 some groups on major problems.
So important is this aspect of our work that we sponsor through a
Meyer Foundation grant a project called  "Professionals in the Public
Interest" which matches volunteer scientists and economists with
citizen groups desiring professional assistance on their projects.
The most recent activity is the  publication of "Public Interest Letter"
which is a monthly report addressed to those who wish to apply their
skills to social action projects.
                              196

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      Second only to group and individual cooperative endeavors in
importance is that of accessibility to the general public.  People
must know who we are,  that we are credible and that we are willing
to listen to their concerns.  Many Americans are desirous of becom-
ing more socially concerned,  but while being scientific experts, they
do not know the art of getting their concerns before the proper
authority. They need to be assured  that their findings be held in
confidence.  They need encouragement in whistle-bio wing.

      A third factor worth considering is credibility.  In order to  be
believed we have to cultivate the mass media, for it can make or
break our final story.  We must foster an active voluntarism in both
resource personnel and in funding sources (usually limited to small
donors and foundations).  We must acquire a certain number of
successes for the track record is always needed for credibility.

      From the public interest staff  standpoint,  a certain flexibility
is paramount.  We must continue to  circulate, to attend scientific
and technical meetings, to consult,  to talk to technical people in
industry and researchers  in universities and to build up a system of
advisors  with whom we can consult on CSPI policies.

      Flexibility is preserved if our system is not totally "systematic".
A pre-alert system which is  overly  systematized is simply not
workable enough to be fully effective.  If bureaucrats construct it
then it's most likely too cumbersome.  For what we are on the look-
out for is precisely the unsystematic in our society, and that can
only be partly found through systematic plodding and investigation.

      The complementarity of the systematic and the nonsy sterna tic,
of art and science,  and of intuition and logic, has been known since
the dawn  of philosophical thought. *  Signalling an alert to a problem
includes an awareness  of an unsystematic happening, a recognition
that it can be systematically assessed, and the  intuitive skills  of mak-
ing the initial findings public. Man's activities are both systematic
and nonsystematic. When they are exclusively one or the other there
is trouble.  An overly systematic person may work to maximize
profits oh a substance and tend to overlook its potentially harmful
effects.   On the other hand, one not fully in tune with that particular
system can ask the critical question which leads to the discovery of a
harmful material.
* For more on this subject of epistemology read B. J. Lonergan's Insight, A Study of Human
 Understanding.
                              197

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                            PROCEDURES
                           Initial Screening
      An accessible,  cooperative, credible and highly flexible public
 interest center can be hindered by a flood of comments, tips,  articles
 and complaints. About half can be either dismissed or routed to
 other groups immediately for investigation.  A certain intuition can
 divide the others into possible problems and more highly probable
 problems.  In the first category more information would be required
 from the one giving the first alarm.  The motivation of the whistle-
 blower may vary from the  sincere technical expert  to the washed
 out worker who wants a face-saving reason for terminating a job or
 getting even with someone.  He may have found an unusually high
 incidence of a rare disease traceable to a toxic substance or he may
 be a kook.

      Three techniques for initial review are possible:  actual contact
 with the whistle-blower, or, if that is impossible, a written or
 phoned request for additional information; inquiry into the credibility
 of the person; review in confidence of the subject matter presented.
 Next, samples and/or procedures where required should be submitted
 to independent laboratories for analyses.  This, however,  can become
 quite expensive for public interest groups.  Both the lab results and
 materials submitted by the whistle-blower should be presented to
 advisors for general comments.   They have saved CSPI much time
 and added efforts.
                  Assembling Material for Evaluation
      Once the initial screening is completed the available evidence
must be weighed.  This includes answering as many questions as
possible about the amount of a material produced or distributed, the
number of persons exposed, the seriousness of the  suspected malady,
the anticipated increase in use  of substance, the type of regulation
required and - most importantly from a political viewpoint — what
alternatives exist which can be easily substituted without unduly
disrupting our national economy.  Face it, economics pulls more
weight on Capitol Hill than does health.
                                198

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      In Washington human resources are available for a proper
assessment:  willing experts in governmental agencies; offices of
professional and trade associations; private foundations and even a
host of experienced retirees willing to investigate problems.  Also
there are many libraries as those at NIH, the Departments of
Agriculture, Commerce, Interior, the Library of Congress plus  the
American Chemical Society library and a number of good  specialized
sources of information such as  the American Petroleum Institute or
the Chemical Manufacturers' Association.

      Once  the data is collected we attempt to assemble the relevant
materials in a  report, which is not a final document but a blueprint
for action on a particular problem.  The report passes through the
hands  of about  a half dozen reviewers who have a variety of technical
skills  and backgrounds.  Generally we prefer face to face confronta-
tions with the critics so that the remarks are fully understood.  We
try to  do  this before the final touches  are on  the report to prevent
personal  bias of the writer from standing in the way of critical
evaluation.
                        The Alert is Sounded
      With the report on the toxic substance accepted, we then begin
to enter a most critical stage:  the presentation of the matter to the
public.  Here several alternatives should be weighed. It might be
better to work quietly within governmental agencies if there is
some degree of success promised by responsible people there.   It
might be best to blast the findings across the wire services  and TV
networks.  This tactic  may seem jarring to you because it goes
counter  to the  scientific practice of never saying anything until
everyone knows for certain.  Incidentally,  social action is the only
practice among scientists which demands certainty; even their
research findings can be quite uncertain if they get them published.

      The type of activity should not be limited to mere  publicity
or threat of legal action.  Actual teaming with pro bono lawyers and
discussing the matter is important as well as examining the possi-
bility of testifying at appropriate congressional committees, organiz-
ing citizen groups to lobby for needed legislation and regulations,
and formation of coalitions of citizen groups  to  apply the proper
pressure for action. We recommend a holistic approach of trying
to get several courses  of action undertaken simultaneously.  Such
                                199

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can be done by mapping out the many places where a contaminating
substance is used and which regulations exist for curbing it.
Specific Examples

      Here are three examples of where a prealert warning method
has  been applied:
      (1)  Toxic Substance Understood but Use Overlooked  CSPI has
 been working on asbestos problems for about two years and our
 research associate, Barry Castleman,  has facilitated research by
 independent laboratories.   We found that asbestos is present in
 alcoholic beverages through the use  of filters made from asbestos.
 We examined a number of sources of drinking water which was carried
 through asbestos cement pipe and found fibers in drinking water.
 This was confirmed by an earlier Johns-Manville report.  We have
 taken a number of steps beyond writing an asbestos report (Asbestos
 and  You):  joint action with EDF prodding FDA to ban use of asbestos
 filters and talcs  in foods,  drugs and drinks; petition to FTC to place
 propert warnings on asbestos products; and a petition  to the EPA to
 prohibit the use of asbestos cement pipe for drinking water.  All of
 this  is part of a prealert on a well-known carcinogenic material in
 product lines which have been overlooked.
      (2) Allied Chemicals to Known Toxic Ones  We have been work-
ing on gasoline additives for a number of years.  A number of the
additives  listed are quite harmful to people,  but these have been
overlooked due to the toxicity of gasoline itself.  We are particularly
alarmed about such materials  as TCP (especially in oil) and Ethyl's
manganese gasoline antiknock which might become more popular if   \
lead is  successfully phased out.
      (3) Toxic Substances Previously Overlooked  In a recent report
"How Aerosols can Affect your Safety and Health",  we have tried
to present a summary of the toxic effects of various household
aerosol sprays.  We raised the question of increasingly numerous
incidents  of misuse.  Hazards can arise from exposure to the freon
propeilants and active ingredients, use  in close quarters,  failure to
read labels and follow directions, propensity for abuse by adolescents,
and availability to small children. A number of aerosols can more
                                200

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easily lead to trouble such as the caustic oven cleaners and air
fresheners.  Our report caused the Consumer Product Safety Com-
mission to call for the first public hearing of the Agency later this
month.

      There are a number of other issues which have been examined
and acted upon.  Some point to immediate alerts  and some such as
our fluorides  study show no need for alarm.  We admit that the
method of alerting will be  subject to fuller development, but we are
confident that a public interest element will be needed for some
time  to encourage proper monitoring of our use of chemicals.
                                  201

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 BIBLIOGRAPHIC DATA
 SHEET
1. Report No.
            3. Recipient's Accession No.    I
4. Title and Subtitle
 Papers Presented At A Seminar on  Early Warning Systems for
 Toxic  Substances
                                                   5. Report Date
                                                     Jan.  30 - Feb.  2, 1974
                                                   6.
 7. Author(s)          Battelle  Memorial  Institute
 Cosponsored  by:  EPA. NIEHS. NSF	
                                                   8. Performing Organization Kept.
                                                     No.
9. Performing Organization Name and Address
 Battelle Memorial  Institute
 Battelle's  Seattle  Research Center
 Seattle, Washington
                                                   10. Project/Task/Work Unit No.
                                                   11. Contract/Grant No.
 12. Sponsoring Organization Name and Address
 EPA  -  Office of Toxic Substances
 401  M  Street, S.W.
 Washington,  D.C.   20460
                                                   13. Type of Report & Period
                                                      Covered
                                                   14.
 15. Supplementary Notes
 16. Abstracts
           A collection of papers  presented at  the Conference on
     Early Warning for Toxic Substances  held at  Seattle,  Washington,
     January 30 -  February 2, 1974.
 17. Key Words and Document Analysis.  17o. Descriptors
17b. Identifiers /Open-Ended Terms

                early warning

                toxic substances
17e. COSATI Field/Group  Q6/F,T
                   pollutant  prioritization
                   hazard ranking
               07/B.C
 8. Availability Statement

 Release Unlimited
19.. Security Class (This
   Report)
     UNCLASSIFJ
WL&
urity Cli
                                                                        ass
                                       20. Security

                                           81jNCLASSIFIED
                                                                              is
                                                              21. No. of Pages

                                                                    215
                       22. Price
FORM NTis-88 (REV. to-78)  ENDORSED BY ANSI AND UNESCO.
                                THIS FORM MAY BE REPRODUCED
                                                                                     USCOMM-DC 8263-P74

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FORM NTIS-38 (REV. 10-73)                                                                                  USCOMM-DC 8288-P74
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