PB-239 416
EPA SYMPOSIUM-ALTERNATIVE CHEMICALS PROGRAM WITH
AN OVERVIEW OF PESTICIDE RESEARCH AND DEVELOPMENT,
HELD AT DENVER, COLORADO ON 14-16 AUGUST 1974
ENVIRONMENT AT, PROTECTION AGENCY
AUGUST 1974
DISTRIBUTED BY:
National Technical Information Service
U. S. DEPARTMENT OF COMMERCE
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'•*•«>*<
EPA SYMPOSIUM
ALTERNATIVE
CHEMICALS PROGRAM
WITH AN OVERVIEW OF
PESTICIDE
RESEARCH & DEVELOPMENT
STOUFFER'S DENVER INN
DENVER, COLORADO
August 14- 76,
EPA-540/9-75-002
II
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TABLE OF CONTENTS
WEDNESDAY. AUGUST 14. 1974 - FIRST DAY
FUNCTIONS AND OVERVIEW OF THE OFFICE OF PESTICIDE PROGRAMS:
HIGHLIGHTS OF OPP PROGRAMS
Dr. Henry J. Korp 1
THE SUBSTITUTE (ALTERNATIVE) CHEMICALS PROGRAM: PURPOSE,
ORGANIZATION, OPERATION
Dr. Leonard R. Axelrod , 9
THE ALTERNATIVE CHEMICALS PROGRAM: FLOW CHARTS AND KEY
DECISION POINTS
Mr. Kenneth O. Olsen 27
OFFICE OF PESTICIDE PROGRAMS LIAISON
Dr. Frederick W. Whittemore 39
INITIAL SCIENTIFIC REVIEW
Dr. Thomas D. Burkhalter 47
THE MINI-ECONOMIC REVIEW
Mr. Jeff Conopask 55
BIOSPHERE REVIEW
Dr. Lamar B. Dale, Jr 61
THE SOCIOECONOMIC REVIEW
Dr. Arnold L. Aspelin 69
PROGRESS IN EPA RESEARCH: NEW DIRECTIONS AND OVERVIEW
Dr. John L. Buckley 99
TOWARDS A NEW PERSPECTIVE ON PESTICIDES
Dr. Henry J. Korp 109
THURSDAY. AUGUST 15. 1974 - SECOND DAY
OVERVIEW OF WORLDWIDE PESTICIDE RESEARCH
Dr. Morris Cranmer 117
WORLDWIDE PERSPECTIVES OF PESTICIDE RESEARCH
Dr. Frederick Coulston 125
THE ROLE OF THE WORLD HEALTH ORGANIZATION IN PESTICIDE
RESEARCH
Dr. Frank C. Lu 147
THE ROLE OF THE FOOD AND AGRICULTURE ORGANIZATION IN
PESTICIDE RESEARCH
Dr. Edgar E. Turtle 161
U.S. PARTICIPATION IN CODEX
Mr. Lowell L. Miller 171
III
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TABLE OF CONTENTS - Continued
SECOND DAY - Continued
SOME PREREQUISITE CONDITIONS FOR THE DETERMINATION AND
EFFICIENT REALIZATION OF THE ALTERNATIVE CHEMICALS PROGRAM
IN SOME EUROPEAN AND DEVELOPING COUNTRIES
Prof. Radojica Kljajic 181
NATIONAL ENVIRONMENTAL PESTICIDE MONITORING PROGRAM
Dr. William S. Murray 197
PESTICIDE RESEARCH IN THE U.S. DEPARTMENT OF THE INTERIOR
Mr. Jerry R. Longcore 213
FROM INDUSTRIAL R&D TO THE MARKETPLACE
Dr. Edwin F. Alder 225
RESEARCH AND SPECIAL CONSIDERATIONS: NONAGRICULTURAL
USE PESTICIDES
Mr. Melvin Garbett 241
THE FUTURE OF PESTICIDE RESEARCH: A CHALLENGE
Dr. Leonard R. AxelrocI 247
FRIDAY, AUGUST 16, 1974 - THIRD DAY
PESTICIDES RESEARCH IN THE ENVIRONMENTAL PROTECTION AGENCY
Dr. John L. Buckley 253
OVERVIEW OF ECOLOGICAL EFFECTS
Dr. Norman R. Glass • 257
TERRESTRIAL EFFECTS
Dr. James Gillett 261
MARINE LIFE
Dr. Thomas W. Duke . • • 263
FRESH WATER EFFECTS
Mr. John G. Eaton 267
PRELIMINARY SYSTEMS ANALYSIS AS A TOOL FOR DESIGN OF
RESEARCH PROGRAMS
Mr. James Hill, IV 275
INTRA- AND EXTRAMURAL HEALTH EFFECTS RESEARCH
Dr. Ronald F. Baron 299
LONG-RANGE HEALTH EFFECTS
Dr. John L. Buckley . 311
APPENDIX I - AGENDA
APPENDIX II - PARTICIPANTS
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FUNCTIONS AND OVERVIEW OF THE OFFICE OF PESTICIDE PROGRAMS:
HIGHLIGHTS OF OPP PROGRAMS
Henry J. Korp, L. L. D. *
I am most pleased to see you all and to have the opportunity of welcoming
you to our conference on the Alternative Chemicals Program. I am delighted with
the fine national and international representation we have here today — surely
there are no significant aspects of pesticides research activities which are un-
familiar to this gathering. The diversity of expertise and backgrounds in this
room is most impressive, and on behalf of EPA, I say thanks to each of you for
your Interest and participation in what we feel will be a very informative and pro-
ductive session for us all.
It's good to see many of my old friends here today, and also to see many
whom I had the pleasure to meet for the first time last night and this morning. To
those of you I am meeting for the first time, I'd like to introduce to you the basic
functions of the Office of Pesticide Programs and to explain our overall attitude
toward the regulation of pesticide chemicals.
Certainly the amendments to the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA) passed by the Congress 2 years ago this October have
to a great extent defined our direction and objectives. I think it Is most helpful
to keep In mind the reasons the FIFRA amendments were Initiated In the first
place. The House Agriculture Committee, which, as you know, designed the
amended legislation, described the reasoning behind the legislation in the follow-
ing manner.
*Deputy Assistant Administrator for Pesticide Programs, U.S. Environmental
Protection Agency
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... the Committee found the greatest need for revision of exist-
ing laws to be in the area of strengthening regulatory control on
the uses and users of pesticides; speeding up procedures for
barring pesticides found to be undesirable; streamlining pro-
cedures for making valuable new measures, procedures, and
materials broadly available, strengthening enforcement pro-
cedures to protect against misuse of these biologically effective
materials; and creating an administrative and legal framework
under which continued research can produce more knowledge
about pesticides as well as developing alternative materials and
methods of pest control ... old FIFRA is changed from a
labeling to a regulatory program.
The FIFRA amendments, if I may oversimplify, reflect the recognition of
an Important concept — that as our knowledge about pesticides and their fate in the
environment has increased, so has our need to possess the administrative tools to
effect regulation of these substances commensurate with this ever-increasing
degree of scientific expertise. Amended FIFRA provides us with the flexibility
to respond to a dynamic situation. The more we discover, the better we can under-
stand the priorities of environmental quality, and the better we can discern and
avoid, to use a phrase oft employed in the FIFRA amendments, "unacceptable
hazards to man and the environment. "
Often, when I explain the function of the Office of Pesticide Programs, I
discuss with my listeners a long established precept of our Agency: That our job
Is to ensure that the benefits of the use of any given registered pesticide outweigh
the risks which could accompany such use. If I'm lucky, no one asks me exactly
how we accomplish this evaluation! Certainly, there are no magic formulas for
weighing the benefits and risks of a pesticide's use and for reducing a myriad of
data to a single infallible truth. We all know that there is a certain inherent risk
in the use of any pest control chemical. This fact is recognized in every registra-
tion action, and is recognized in our continuing post-registration reviews. We
don't cancel a product's registration simply on the basis that a risk is posed by
its continued use.
2
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FUNCTIONS AND OVERVIEW OF THE OFFICE OF PESTICIDE PROGRAMS:
HIGHLIGHTS OF OPP PROGRAMS
Henry J. Korp, L. L. D. *
I am most pleased to see you all and to have the opportunity of welcoming
you to our conference on the Alternative Chemicals Program. I am delighted with
the fine national and international representation we have here today — surely
there are no significant aspects of pesticides research activities which are un-
familiar to this gathering. The diversity of expertise and backgrounds in this
room is most impressive, and on behalf of EPA, I say thanks to each of you for
your Interest and participation in what we feel will be a very informative and pro-
ductive session for us all.
It's good to see many of my old friends here today, and also to see many
whom I had the pleasure to meet for the first time last night and this morning. To
those of you I am meeting for the first time, I'd like to introduce to you the basic
functions of the Office of Pesticide Programs and to explain our overall attitude
toward the regulation of pesticide chemicals.
Certainly the amendments to the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA) passed by the Congress 2 years ago this October have
to a great extent defined our direction and objectives. I think it Is most helpful
to keep in mind the reasons the FIFRA amendments were initiated in the first
place. The House Agriculture Committee, which, as you know, designed the
amended legislation, described the reasoning behind the legislation in the follow-
ing manner.
•"Deputy Assistant Administrator for Pesticide Programs, U.S. Environmental
Protection Agency
-------
... the Committee found the greatest need for revision of exist-
ing laws to be in the area of strengthening regulatory control on
the uses and users of pesticides; speeding up procedures for
barring pesticides found to be undesirable; streamlining pro-
cedures for making valuable new measures, procedures, and
materials broadly available, strengthening enforcement pro-
cedures to protect against misuse of these biologically effective
materials; and creating an administrative and legal framework
under which continued research can produce more knowledge
about pesticides as well as developing alternative materials and
methods of pest control ... old FIFRA is changed from a
labeling to a regulatory program.
The FIFRA amendments, if I may oversimplify, reflect the recognition of
an Important concept — that as our knowledge about pesticides and their fate in the
environment has increased, so has our need to possess the administrative tools to
effect regulation of these subsfances commensurate with this ever-increasing
degree of scientific expertise. Amended FIFRA provides us with the flexibility
to respond to a dynamic situation. The more we discover, the better we can under-
stand the priorities of environmental quality, and the better we can discern and
avoid, to use a phrase oft employed in the FIFRA amendments, "unacceptable
hazards to man and the environment. "
Often, when I explain the function of the Office of Pesticide Programs, I
discuss with my listeners a long established precept of our Agency: That our job
is to ensure that the benefits of the use of any given registered pesticide outweigh
the risks which could accompany such use. If I'm lucky, no one asks me exactly
how we accomplish this evaluation! Certainly, there are no magic formulas for
weighing the benefits and risks of a pesticide's use and for reducing a myriad of
data to a single Infallible truth. We all know that there is a certain Inherent risk
in the use of any pest control chemical. This fact is recognized in every registra-
tion action, and Is recognized in our continuing post-registration reviews. We
don't cancel a product's registration simply on the basis that a risk Is posed by
Its continued use.
2
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If there Is reason to believe that the risk is greater than was anticipated at
registration, though, we are most concerned and conduct a thorough evaluation of
the situation, we ask ourselves about the ways that these risks can be reduced and
the extent to which they can be reduced. How far can labeling go toward this end?
Or other restrictions — use restrictions (as will be provided by our regulations
implementing section 3 of the amended Act), geographic area restrictions, inte-
grated management program restrictions, packaging restrictions, formulation
variables, and so on? The new Act unquestionably provides us with a great deal
of flexibility In taking action short of cancellation. And on the benefit side — how
crucial is the use ? Is It necessary to Public Health Programs or a major food
source, or Is It directed toward a nuisance or Inconvenience? These, among many
other significant factors, are the questions we must ask ourselves In assessing the
continued use of pestlcloa products. And another factor Is important too, of course,
which is the reason we're together here today: What alternatives does society have
to the pesticide in question? Are these alternatives more or less acceptable from
the standpoint of human health and environmental well-being In general? These
are questions of crucial Import, and we will quite obviously discuss these issues
In depth as this conference progresses.
These are some of our fundamental considerations in pesticides regulation,
and our Office of Pesticide Programs Is naturally concerned In an overall way with
meeting the challenges of the complex decisions-making progress In this important
area. As promised, though, I'd like to explain briefly more about the organization
of OPP, and the various functions exercised by our four divisions: Registration,
Operations, Technical Services, and Criteria and Evaluation. Those familiar
bear with me.
The Registration Division is headed by Mr. John B. Ritch, Jr., as Director.
As our friends In industry know well, the two primary functions of this Division
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are to register individual pesticide products and to establish residue tolerances.
The Division reviews the data submitted by an applicant to ensure that all the
criteria for registration are met before an EPA number is assigned.
The Registration Division has a tremendous job ahead In the next 2 years.
There are approximately 34,000 products currently registered which must be re-
registered under section 3 of the amended FIFRA and classified for general or
restricted use. In addition, approximately 15,000 intrastate products must be
classified and registered. All of this, of course, is in addition to the normal
workload of the Division, which conducts around 15,000 actions a year.
Our Operations Division Is headed by Dr. John V. Osmun, and Is respon-
sible for the development of programs to enhance the effectiveness of Governmental
activities in the pesticide area. This Division provides program policy direction
to technical assistance and training programs. Operations was responsible, for
example, for EPA's part In Project Safeguard, which was a program conducted
last year in the South to train applicators In the use of parathion and other highly
toxic organophosphates. Operations also develops and recommends program con-
tent and model legislation for states and, through the Regional Offices, assists
states in developing and improving their individual programs. This Division also
participates in Federal Interagency activities In the pesticide area and coordinates
information on pesticide accidents and incidents.
One of the biggest jobs undertaken by Operations has been the development
of the regulations to implement section 4 of the amended Act, which concerns the
certification of pesticide applicators to employ restricted use pesticides. Defining
the procedures for certification has been a complex task, and we have solicited
comments from the pesticide Industry, farm oriented associations, and other
interested parties in writing these difficult regulations, which we hope to publish
as final very shortly. Operations is, of course, also working very closely with
the states in developing plans to conduct the actual certification of pesticide
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applicators. As most of you know, I am sure, our goal is to have all those who so
desire, to be certified to use restricted pesticides by October 1976.
Our Technical Services Division, whose Director is Dr. William S. Murray,
is responsible for the performance of laboratory investigations needed by OPP. The
Division conducts epidemiological studies of various exposed population groups and
seeks information on the potential effects of these exposures on the induction of
harmful health effects. Technical Services has the responsibility for operating,
planning, designing, and interpreting data collected in the National Pesticide Moni-
toring System, which includes operating and coordinating responsibility for moni-
toring pesticide residue levels In air, water, soil, crops, livestock and aquatic and
land animals. Another of its primary functions is in the Systems and Information
side of our program, which Includes the development, operation, and maintenance
of data storage and retrieval systems in OPP, and publishing of two periodicals,
the Pesticides Monitoring Journal and the Health Aspects of Pesticides Abstract
Bulletin. Technical Services also prepares the "Compendium of Registered
Pesticides," which is familiar to many of you.
I know I don't have to Introduce the Director of the Criteria and Evaluation
Division, Dr. Leonard Axelrod, to you, since he has arranged this conference and
invited you here. Criteria and Evaluation Is responsible for the establishment of
standards and criteria to be applied In the setting of tolerances and environmental,
human safety, and efficacy standards applicable to the registration of pesticide
products. One of its primary functions Is to review currently registered pesticide
chemicals and recommend to me appropriate regulatory actions as Indicated by it's
findings. The reviews include the assessment of environmental, human and wild-
life safety, economic aspects, and all other pertinent ingredients In the risk-benefit
analysis. And, of course, the Alternative Chemicals Program Is part of this
responsibility. The Criteria and Evaluation Division also provides technical support
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to the Office of Enforcement and General Counsel necessary to the conduct of
administrative hearings and regulatory actions. Appropriate guidelines, standards
and criteria needed by other components of EPA and other governmental agencies
are developed, based on a comprehensive assessment of pesticides and their im-
pact on the environment. Research needs for OPP are developed and transmitted
to the Office of Research and Development, and monitoring requirements for pesti-
cides are developed and program policy direction to monitoring activities is
provided. C&E is also responsible for the major preparation of the "Guidelines
for Registering Pesticides in the United States," which we anticipate will be a
great help to applicants; this document explains in detail the type of information
needed to obtain registration. We expect to have the "Guidelines" published by
October of this year.
As far as our goals are concerned, we have four major strategies which we
hope to accomplish in the coming years.
1. First, and most obvious, is to promulgate the regulations necessary to
fully implement the FIFRA amendments. This task must be completed by October
1976.
2. Secondly, we desire to reduce adverse health and environmental effects
from the use of pesticides. We anticipate accomplishing this goal through the
»
certification of applicators, improved labeling and packaging of pesticide products,
timely enforcement against misuse, public education programs, and whatever other
regulatory actions we discern are needed.
3. Thirdly, we Intend to establish a better comprehensive hazard .evalua-
tion system to better understand the nature and extent of adverse effects of pesti-
cides on man and the environment.
4. And, of course, our other goal is to assess the technological, economic,
social, and physical environments related to pesticide use and to determine the
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changes occurring to operating environments. Principal near-term research
emphasis will be place on:
t Generating data to support current and anticipated litigation
• Devising standardized laboratory test methodologies
• Developing model ecosystems
• Exploring alternative pesticide possibilities
Before closing, I would like to emphasize that we are here today to share
our thoughts and intentions with you and to explain expressly our plans and the
reasons behind them. The Office of Pesticide Programs is most concerned to
conduct its business with the maximum of openness in all aspects of our program
development. We have no intention of secretly devising any great schemes which
we can suddenly thrust on the unsuspecting public. On the contrary, we welcome,
we solicit, the comments and advice of all who will be affected by our regulatory
activities. This conference will be a magnificent opportunity for us to explain our
policies and to clear up or avoid any misunderstandings or apprehensions which
you may have. We desire to put this Alternative Chemicals Program In perspective,
to discuss how it fits into our research and program objectives as a whole, and to
find out your feelings and opinions on the Issues. In short, we want this conference
to be a sharing of information and thoughts. I very sincerely thank all of you for
participating In this sharing process. I know that together we can make great
progress In contributing to a finer environment for us all.
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THE SUBSTITUTE (ALTERNATIVE) CHEMICALS PROGRAM:
PURPOSE, ORGANIZATION, OPERATION
Leonard R. Axelrod, Ph. D*
In 1973, the House Appropriations Committee, Subcommittee on
Agriculture-Environmental and Consumer Protection appropriated $5 mill-
ion for fiscal year 1974 to the Environmental Protection Agency to "provide
for research on and testing of substitute chemicala" (Public Law 93-135). The
legislative intent for this Public Law and action can be found in the Congress-
ional Record of November 6, 1973, L. e., "for the testing of substitute chemicals
by EPA — to avoid taking action based on insufficient knowledge as has been done
in the pact."
Summation o.v this intent otherwise stated is to prevent the use of
substitutes for deregistered pesticides which in essence are more deleterious
than the original to man and the environment. The thrust of this legislative
Intent was derived from the uses of some 70 presently registered substitutes
for DDT, but it also seeks to prevent such problems in the future when dealing
with other substitutes now and In the future considered too hazardous for use
In the United States.
The Substitute Chemicals Program has four principal objectives.
The first Is to identify suitable substitutes (alternatives), insofar as possible,
for products and/or uses, both major and minor, which (a) are under internal
review and therefore possible candidates for cancellation, (b) are In litigation
for cancellation or suspension, or (c) have been canceled or suspended. The
second Involves studies to develop reliable and hopefully economically feasible
screening methodologies for evaluating pesticides under review In the areas of
*Dlrector, Criteria and Evaluation Division, Office of Pesticide Programs, U.S.
Environmental Protection Agency
Preceding page blank
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toxicology and safety, where there is such a need as for the "genesis" and repro-
ductive problems. The third is to do research which fills certain gaps of know-
ledge in the areas of toxicology, ecology, and chemistry needed to flush out the
data bases for the review of suitable substitutes. The fourth is to stimulate,
through.liaison efforts with industry, the research and development required to
register new pesticides in specific areas of the agricultural sector needed as suit-
able substitutes.
Three subprograms have been developed:
The Reviews Process — First, the initial scientific review to study the
relative safely of the substitute chemical. A look at the top of the mountains
(Figure 1). Is there an obvious problem?
Figure 1
Initial Scientific Review
The "Topi of tin Mountains"
National
Diet
(Market
basket)
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Second, the mini -economic review — an overview of the use patterns of a
substitute and an estimate of the amount used annually in each pattern. This review
identifies basic producers and performs an initial analyses of the economic bene-
fits, by use, of the pesticide. It develops an initial view of the relative cost-
efficiency data related to the pesticide uses.
If a problem seems to have emerged, then full biosphere and socio-
economic studies are developed (Figure 2). If no problems are foreseen in the
substitute uses and projected increased uses of the substitute, then the compound
will be cleared through the reregistration process.
It should be stated at this time that a review of a substitute does not
imply evidence of an adverse effect. It only means that the substitute has been
apparently successful as an alternative to the canceled or suspended pesticide
uses, or that it is likely to be put into place by the agricultural sector as an
alternative.
Figure 2
Information Sources:
Industry
Academia
Government
International (e.g. WHO/FAO)
Socio-
economic
Reviews
Risk/Benefit
Analyses
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Actually, some confusion has existed with the term review in the Office
of Pesticide Programs (OPP). There are four types of reviews progressing
simultaneously in the OPP which are separate in thrust, intent, and meaning,
as follows:
The registration review of a new pesticide seeks to review the data
for both safety and efficacy as far as can be determined for a new pesticide use
by present toxicological and environmental standards of testing.
The rereglstration review, carried out in the Registration Division,
seeks to determine If, after 5 years of use, the pesticide by company data and
other exogenous inputs still passes the minimum required standards of safety
and efficacy. It should be stated, however, that large numbers of pesticide
registrations have never gone beyond an acute toxiclty study and for those
registrations on food and feed not beyond a subacute or 90-day study.
In the recent few years, certain chronic toxlcity studies have been
required and reviewed in registration for development of tolerances and ADI's
for these pesticides, primarily for new pesticides. It should be pointed out that
many presently registered pesticides were registered on the basis of required
tests 10 to 25 years ago, and a different philosophy of the role of safety in man and
his environment has since developed. The FIFRA, as amended, seeks to adopt
new avenues of study for the reregistratlon process.
The internal review of a pesticide and Its uses carried out in the Criteria
and Evaluation Division Initiates from extra-agency Inputs such as major reports to
the nation on health; Congressional Inquiry either direct or through GAO; Incidents
leading to requests from environmental groups; NIH, FDA, and NCTR reports; or
new data reported in the academic literature from laboratory or field experiences.
Any or all of these types of reports have one thing In common. They report data for
human Incidence, animal experimentation, or environmental findings that Imply un-
reasonable adverse effects to man or his environment. The internal review is
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developed to determine the credibility of these claims and the decision that if by
all studies — economic, social, and scientific — the pesticide use still represents
an unreasonable risk to man or his environment when compared to the benefits it
represents, suggested action for cancellation or suspension of its uses be taken by
the Administrator.
The substitute chemical program review carried out as a joint effort of the
Criteria and Evaluation Division (C&E) and the Office of Research and Development
(R&D) seeks to establish the credibility of a pesticide and its uses as a substitute for a
canceled, suspended, or litigated pesticide and its uses.
The Liaison Effort Is directed to all activities involved with research,
development and manufacture, and use of pesticide products. Much of the liaison of
the Alternative Chemicals Program will be conducted through this symposium and
informal work sessions which will serve as the focal point for all information exchange
and work priority setting. Liaison will be concerned primarily with the following:
o Present the progress of the various alternative chemicals research
programs
« Identify data requirements to be derived from the various R&D sources
available to the program to support the reviews
9 Develop criteria for pesticide alternatives for special or unique uses
• Suggest solutions to special problems evolving from the review or
scientific needs
The liaison program is envisioned to be beneficial in the following areas:
(1) offer broad technical information and data support from government and industrial
sources to the C&E staff performing the reviews for the program; (2) review, on
an individual company basis at EPA, the results of the Initial Scientific and
Mini-Economic studies; (3) expedite product and R&D efforts: and (4) aid in the
retrieval of data not generally available in the literature or EPA files.
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Finally, the third subplan, Research in support and development of sub-
stitute (alternative) pesticides. This program encompasses a considerable portion
of the appropriation. Dr. Buckley and his group will present the main thrusts of
*, ' ' •
the Office of Research and Development's areas of interest and concern. OPP has
for the program needs, thusfar instituted studies on new, more effective, more
credible and predictive screens for the genesis problem — primarily carcino-
genesls and mutagenesls; studies on early warning systems for safeguarding and/or
early alerting of applicators and users of hazardous levels of organophosphates and
carbamates; and studies on a better understanding of the modes of action of the
herbicides.
QUESTION: I understand this Initial scientific review, the actual existence
of four conditions of review.
DR. LEONARD AXELROD: I am glad you brought that up. Substitute chemi-
cal review as a part of Initial scientific review. The other reviews, the registration,
the rereglstratlon, and the internal reviews have nothing to do with this aspect we
will discuss today. There are other types of review in the Agency and we must not
confuse these.
QUESTION: That's exactly the heart of the question. Are we talking about
different people conducting the Substitute Chemical Program Review than those
people that are conducting the registration reviews and so on and so forth?
14
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developed to determine the credibility of these claims and the decision that if by
all studies — economic, social, and scientific — the pesticide use still represents
an unreasonable risk to man or his environment when compared to the benefits it
represents, suggested action for cancellation or suspension of its uses be taken by
the Administrator.
The substitute chemical program review carried out as a joint effort of the
Criteria and Evaluation Division (C&E) and the Office of Research and Development
(R&D) seeks to establish the credibility of a pesticide and its uses as a substitute for a
canceled, suspended, or litigated pesticide and its uses.
The Liaison Effort Is directed to all activities involved with research,
development and manufacture, and use of pesticide products. Much of the liaison of
the Alternative Chemicals Program will be conducted through this symposium and
informal work sessions which will serve as the focal point for all information exchange
and work priority setting. Liaison will be concerned primarily with the following:
• Present the progress of the various alternative chemicals research
programs
• Identify data requirements to be derived from the various R&D sources
available to the program to support the reviews
« Develop criteria for pesticide alternatives for special or unique uses
• Suggest solutions to special problems evolving from the review or
scientific needs
The liaison program is envisioned to be beneficial in the following areas:
(1) offer broad technical information and data support from government and industrial
sources to the C&E staff performing the reviews for the program; (2) review, on
an individual company basis at EPA, the results of the Initial Scientific and
Mini-Economic studies; (3) expedite product and R&D efforts: and (4) aid in the
retrieval of data not generally available in the literature or EPA files.
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Finally, the third subplan, 'Research^in support and development of sub-
l ' ' .'•
stltute (alternative) pesticides. .This program'encompasses a considerable portion
• *•* ..'•',' ^ .'••..'
of the appropriation. Dr. Buckley and-hls group will present the main thrusts of
the Office of Research and Develppinent's atfeas of interest and concern. OPP has
..• '"' '.! •'••• . ' |
for the program needs, thusfar instituted studies on new, more effective], more
1 •'• • -;, ,;
credible and predictive screens for the genesis problem — primarily carctno-
genesis and mutagenesis; studies on early warning systems for safeguarding and/or
1
early alerting of applicators and users of hazardous levels of organophosrihates and
carbamates; and studies on a better understanding of the modes of action ^f the
herbicides.
QUESTION: I understand this Initial scientific review, the actual existence
of four conditions of review.
DR. LEONARD AXELROD: I am glad you brought that up. Substitute chemi-
cal review as a part of initial scientific review. The other reviews, the registration,
the reregistratlon, and the Internal reviews have nothing to do with this aspect we
will discuss today. There are other types of review In the Agency and we must not
confuse these.
QUESTION: That's exactly the heart of the question. Are we talking about
different people conducting the Substitute Chemical Program Review than those
people that are conducting the registration reviews and so on and so forth?
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DR. AXELROD: The registration reviews which are developed primarily on
an ad hoc basis and are after October guided by guidelines for registration are done
by one set of people, obviously in the registration division. The reviews which are
internal, called internal reviews and substitute chemical reviews, are done by other
scientists in the Criteria and Evaluation Division. But the thrust, the intent of these
reviews is different, each to each own, and each to its own need, which I thought we
brought out by talking of the credibility of claims made against a compound being in
the "Internal Review" for the "suspect chemical" and saying that the alternative or
"Substitute Chemical Review" deals only with establishing the credibility of safety
of the compound with no claims made against this registered substitute.
QUESTION: I understand the philosophy of the whole thing but I have difficulty
in assessing the idea that there are separate groups of people running these reviews
which require a high level of expertise and knowledge about the individual products.
DR. AXELROD: I believe that we have people whose credentials would fit
exactly the bill that you are discussing now. People who have pesticide and specific
scientific expertise to carry out these, but they don't make decisions on their own
necessarily. They do seek help from consulting areas, from Industrial expertise,
and from academic sources. It Is not an Individual's concept that goes forth from
the Agency or from the Office of Pesticide Programs. It Is a conglomerate decision.
DR. HENRY KORP: I can assure you these are different people. If my budget
gets cut as It probably will, suspect chemicals may lose a few people, but I can
assure you It will not be In the area of substitute chemicals. And that was a mis-
sion that was assigned to us by the Congress for at least 1 year and probably 2
years and that was kind of a fixed program to have a group of people to work on that
without any question.
QUESTION: I wonder If this might not get to the heart of the problem and
that Is are the same facts and the same evidence to be used by these two different
groups In connection with the same compound ?
15
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DR. AXELROD: This same compound won't show up In the reviews. The
compounds which are suspect chemicals have nothing to do with substitute chemicals.
Those chemicals which are internally reviewed, given that name, are suspect chemi-
cals. They are not on the program for substitute studies so the thrust, the intent,
and the studies are quite different. Let's just take two I think we are all fairly familiar
with called dleldrln and aldren. If we made a review of those compounds, they would
be Internal reviews. They would be compounds which were suspect due to one or
more of these exogenous Inputs of suspicion, but they would never show up as sub-
stitute compounds on this program.
Literally, the compounds we are looking at have not had any adverse mention
from any source concerning their use pattern or their health effects. It is not the
throist of this program. So Aey are completely different compounds. You cannot
have the same compounds showing up in both places.
QUESTION: In time sequence, however, you can indeed have them showing up
in each place, I believe. First, the new compound is registered on the basis of all
the required data and then as it's used over a period of time, it may become con-
sidered a substitute compound, and with further information it may very well become
a suspect compound.
DR. AXELROD: That's correct.
QUESTION: Now, does it make sense then to have different groups of people
review the same kind of Information as this one compound progresses along this line
of time?
DR. AXELROD: Because you have Instituted an important factor, time, an
expertise in a particular area, let's say a genesis area, may in 10 or 15 years be
there to perform a different type of review. The possibilities of them being there
are not that great but the kind of expertise he brings doesn't depend on himself, it
16
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depends on an information database which is accrued in his professional life and
information which has been accrued in the literature to support his ability to analyze
that data base. The most important concept in science, whether it's in the EPA or
not, is first to have data and then to have people who can scientifically review,
analyze, and enunciate the decision based on that data, and it does not say, in any
sense of the word, that there will not be argument and debate over any one subject.
I don't know lawyers who think the same on all points and I don't know that scientists
concur on the same points.
It was 25 years before Einstein's theory became hypothesis, and there were
arguments as to the validity of his theory well Into the 1930's although enunciated in
1905 by perfectly ethical expertise in the area of theoretical physics. So no one will
stand and tell you that you will not have argument on two sides. It seems to me that
In litigation proceedings that last 8 or 9 months, there are experts on both sides of
the issue.
QUESTION: I don't even agree that there will necessarily be a time frame.
You could be on both lists depending on what the suspicion Is and could be suspect
for one use and an alternate for another use.
DR. AXELROD: This Is true but we are not viewing it and we are not willing
to institute such a duallstlc approach to the subject. We are trying to render unto
Caesar ..what is Caesar's and a compound which Is brought to our attention from the
exogenous information sources as suspect will be treated as an internal review
compound. It does not necessarily in any stretch of the imagination mean that it
will be canceled. It only means that we look at it in the light of establishing the
credibility, right or wrong, of the accusations. But It will not find itself on the list
of substitutes, which doesn't exist officially.
QUESTION: But you hit on It and that Is, did I hear you say that you could
not or would not In the future establish a tolerance based on a 90-day chronic study ?
17
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DR. AXELROD: No, I didn't say that. I said that many of the presently
registered pesticide compounds were established on no further studies than a 90-
day study.
QUESTION: There is a distinct lack of that in section 3 of the present pro-
posed regulations that it would imply that even negligible residue tolerances cannot
be established. This has to be a complete change from what we were seeing, say
6 months ago.
DR. AXELROD: We are not really here prepared to discuss section 3. At
this point in time, nothing of which we are presenting seems to have impact from the
section 3 regulations. These studies are not regulated by section 3.
QUESTION: I wonder if you would comment on your point number four brought
out on the stimulation of research and development. Does this refer to the stimula-
tion of research and development as based upon your reviews on the alternate chemi-
cals or new chemicals?
DR. AXELROD: The whole idea of research and development particularly in
the industrial sector has emerged quite strongly over the last year to my knowledge,
and it has been a subject of discussion not just with the Office of Pesticide Programs
or ORD, but with the Administrator, to stimulate the industrial sector to bring to our
agricultural uses new pesticides for these uses. And part of this program is to stimu-
late research and development to new directions exogenous to the Agency and that is,
to fill data gaps where they exist and to literally anticipate as we go down the line,
substitutes, alternatives for either compounds which don't seem to be effective
as substitutes for deregistered products or canceled products, or in use areas
such as minoiMise areas where there doesn't seem to exist substitutes, i.e. effec-
tive pesticides for .these minor uses.
18
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QUESTION: Do you have any feel at all as to how many products you are
going to be reviewing? Are you going to be reviewing one a year or 10 a year?
Every product that's presently registered? After all, anybody can make an accusa-
tion against almost any product on the market.
DR. AXELROD: That's precisely the attitude which I think is negative and
precisely the attitude we are trying to negatively delineate here. There is no accu-
sation against the substitutes.
QUESTION: Do you have any guidance at all as to how big your program is
going to be ? Are you anticipating that you are reviewing one product a year or 10
products a year?
DR. AXELROD: We can only anticipate those number of products which can
be reviewed according to the resource commitments made to the program, and that
seems to stem directly from Congressional mandate.
QUESTION: Is that going to be one or 10?
DR. AXELROD: It won't be one and I don't know if it will be 10. It depends
on how well things go. This is a new program. Much is to be considered for time.
I certainly think it should be more than one just because you can do more with a
few than you can do with one for the same manhour commitments.
QUESTION: My question goes back to what are the main objectives of the
Substitute Chemicals Program. And as you define them, I understand they include
defining substitutes for products that are under review, products that are under canr-
cellatlon or some suspicion about them, and also products that have been canceled.
Now to me this puts all these products in the category that would be
reviewed by an internal review concern, because an internal review is going on.
DR. AXELROD: "Internal Review" as I have enunciated is a review only
for a compound for which negative Information has been developed. Internal review
only deals with a compound that could be classified as a potential baddy, not as a
goody.
19
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MR. DONALD McCOLLISTER: I think one of the things that's been bothering
some of us is that if another DDT-type material is canceled and there is already
registered a useful material that is commercially available and has a proper label
for use on that crop, then the question is "Where does the Substitute Chemical
Program come In?" As I read It, some of us have felt that the marketplace would
just accept and use this other material.
DR. AXELROD: As it has.
MR. McCOLLISTER: But then all you've added, It seems to me, is this idea
of establishing credibility. Now, I guess the only question Is: "How necessary is that
step except that Congress told you to do It?"
DR. AXELROD: Well, you know, that's a good reason. I mean, we are a
government agency. We are public servants and when someone says do it, you do it.
He's going to give you all kinds of answers, but that's a good answer.
DR. KORP: Technically, It Is a desirable thing to make sure that you are not
using a substitute which may be even more hazardous than the material you have thrown
out. That's really, as Len brought out, a secondary purpose. The fact is we've been
given permission to do It, really, and not a mandate. It makes more sense to me.
DR. AXELROD: Let me say something which doesn't come into the purview
of this delineated program but which Is Important from what you are saying. Judicious
use of pesticides versus ludicrous use that was made of DDT and led to major problems
existing, could be anticipated by this program. It isn't so much the compound you're
using or how much is being used, as to what effects it has in our environment and In man.
I suspect that If the word judicious use of DDT In all areas quantitatively and quali-
tatively had been Implemented, we might not have gotten to the point where such accusa-
tions were made against the compound leading to its final cancellation, and I think it
behooves both the industrial people and the government people to look at these sub-
stitutes now and for future uses to, hopefully, never have to bring forth such a
20
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massive accusation system and legal problem as existed with DDT. One pound
used is one thing and 100 million pounds is another; whether it is persistent or non-
persistent is another, and various and sundry portions of the "tops of those moun-
tains" bring to bear on whether this substitute may get into trouble as DDT itself
did or whether that substitute is a suitable one.
One of our friends in industry has claimed over and over again that a substi-
tute or alternative need not in any way be a real substitute for the stuff you are
knocking out; that substitutes for canceled uses of 2,4,5-T may indeed not be as
effective as the original compound and that fundamentally, at least in a theoretical
consideration, there are no real substitutes for anything. However, there are regis-
tered substitutes.
DR. EDWIN ALDER: Dr. Korp, you have a mandate for a year or perhaps two
from Congress for the Alternative Chemicals Program. If funds are available, do
you see this as a program that would continue beyond the 2-year period ?
DR. KORP: Of course, I have no way of knowing. It depends partially on
our success. Will we really develop something in these first 2 years ? Can we
really develop information which will show these substitutes are better for the
potential or will we have some products "knocked out of the box" ?
We will certainly suggest continuing it if we find it's desirable. If it isn't,
we'll say so, Budgets will be tight so I'd rather do those things that are desirable
and necessary than just carry on a study because it's on the books.
QUESTION: The internal review is separate from the Substitute Chemical
Program and you will not begin a review for a substitute until a product Is "knocked
out of the box," or if it's in the internal review you may pick it up at that point.
What would you consider the reason the product ought to have a study made for
substitutes ?
DR. KORP: Because it is a widely made substitute.
21
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DR. AXELROD: It's the mandate of the program. The mandate speaks that
there is suspicion and it's backed up by law now and money for the law, that some
of the substitutes or the substitutes for DDT were worse in the environment for man
than DDT was, and with no accusations or fingerpointing there are many compounds —
70 in nature as I enunciated — which are registered substitutes for DDT.
QUESTION: My point is if you have a new compound, compound X...
DR. AXELROD: New compound means what in your way of thinking?
QUESTION: Well, a compound that's on the market and somebody says there's
something wrong with this compound and therefore it goes into internal review.
DR. AXELROD: That's not a new compound.
QUESTION: It goes into internal review to see whether or not the accusations
against it are valid.
DR. AXELROD: Yes, that's an internal review compound. That's not a sub-
stitute compound.
QUESTION: My question is now would the Substitute Chemicals Program then
look at that compound and say, "It's under internal review, should we then begin to
find a substitute, " or do you wait until there's a decision made in the internal review?
DR. AXELROD: I think it behooves the scientists in the Agency not to antici-
pate problems before they arise in this area. When a compound is in internal review
and by risk-benefit analysis of rather in-depth studies for health, for toxlcity, for
man, for environment, and for socioeconomic consequences of taking it off shows
that the risks are much greater than the benefits, I think it behooves us to start
seeking out the presently registered substitutes, not necessarily to review them, but at
least to enunciate those compounds which are presently registered as substitutes
and hopefully to stimulate the industrial sector to seek compounds which may be
better for the uses in question, and when one looks at internal review, it is not a
matter of across-the-board either for enunciating the problems; it's a matter for
uses. Use by use is looked at in the internal review for the hazards of the pesticide.
22
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DR, JOHN BUCKLEY: It seems to me that maybe we have some misunder-
standings of what seems to me a simple orderly process. You'll have ample oppor-
tunity to straighten me out on my misconception later on during the week, but the
obligation of EPA in relation to pesticides was clearly stated by Henry Korp in his
opening remarks. And that was that it's our job to see that there are adequate pest
control methods of the optimum degree of safety available to the American public.
So you start the whole business at sort of a level of social trade-offs in terms
of risks and benefits and there are a lot of things that go into that. One thing that
goes into it is hard fact. That's presumably my part of the business — the genera-
tion of data, the validation of data, and its scientific evaluation. Resting on the facts
there will be possible a whole set of decisions, some of which are never made. What's
giving us trouble here is that we don't start at time zero with nothing having been done.
It's an ongoing process. New compounds are being registered and the uses are being
registered. Products are being reregistered. New facts are turning up and on
demand EPA is looking at these to see whether the facts warrant some action or
even if they are facts.
As a separate operation to increase the ability of the Agency to make sensible
trade-off decisions as to what product will be available for which uses for a social
gain of society, one of the things you want to know is whether, in fact, a proposed
action is going to take you from the frying pan into the fire, and we clearly don't want
to be there.
Now, I don't know that there's any instance in time, any exact event which
would trigger a look at a compound as a substitute. It seems to me that if the evi-
dence begins to mount that a particular product that has served us very well in terms
of pest control is likely to have some severe problems and perhaps be less available,
then at least an informal review starts. One of the things you have to know is what it
will cost society. What will we have to get along without? What other things could
be used? This program, as I perceive it, attempts to provide a factual basis for
answering such questions. The program labeled Alternative Chemicals is an integral
part of this whole business of providing the best possible social decisions.
23
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Maybe "social decisions" is only another way of saying risk-benefit, cost-
benefit, or whatever. You can't measure all factors in dollars. Some factors you
really don't have good ways of measuring, but you can at least spell it out and include
it as part of your consideration. That's what Mr. Korp gets paid for, making
that decision or recommending that final decision.
My end of the Agency, my job, is trying to help provide him and his colleagues
who reevaluate and write the criteria, with the best set of facts that will be helpful.
The timing on this is regulated to some degree by the kinds of questions, some of
which can be clearly enunciated today and some of which will arise after we leave
this meeting.
DR. BARRY COMMONER: I would just like to add a few comments to what
John Buckley said. When v'ewed against the background of the National Environmental
Policy Act, the Substitute Chemicals Program takes on a rather general significance.
Everyone is aware of section 102C of that Act which requires the preparation of an
environmental impact statement for any major Federal program. A careful reading
of that section and of the following one makes one realize that built into the Act is
a firm requirement for looking at alternative ways of accomplishing a given program
that might help minimize its impact on the environment.
It might help if we were to see how that approach works in an area that none
of us here is directly connected with. Take for example, the environmental Impact
statement that the AEC filed on the breeder reactor. The statement has been
criticized because it failed to look at alternative ways of producing energy — which
is the purpose of the reactor. This kind of consideration really amounts to a new
stage in the evolution of a national environmental philosophy; it points toward an
approach that is positive rather than negative. After all, the fact is that you have
to have electricity. Once that social necessity is recognized one can begin to see
what range of alternative techniques are available for accomplishing that social
24
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goal, which minimize the resultant environmental hazards. The significance of
introducing alternatives into these considerations is that it sets the social goal
as the target (in this case producing energy) and looks for the best way of achieving
it.
The SCP represents the extension of this new, positive approach to the
pesticide field. Although the SCP arose out of a response to the environmental
challenge to DDT, I believe that it will have a much wider significance. What
the SCP can do is to give society a wider range of alternative ways of accomplishing
what a pesticide is supposed to do — which is to improve food production, for
example. We ought to look at the program as a positive one, rather than as an
extension of the adversary approach that has been charactersitic up to now.
What the SCP does is to extend the scientific base that will be available to us
as we seek to accomplish the social purpose toward which pesticides are, in
principle, directed — the improvement of human welfare.
25
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THE ALTERNATIVE CHEMICALS PROGRAM:
FLOW CHARTS AND KEY DECISION POINTS
Mr. Kenneth O. Olsen*
The work-flow chart and key decision points that will be discussed this
morning reflect the safety reviews of registered substitute chemicals that
will be performed under the Alternative Chemicals Program. These safety
reviews are a major thrust of mis program, and the decisions made during
the review determine the suitability and acceptability of a particular registered
pesticide to act as a substitute chemical.
There are several other major decisions that must be made independent
of the safety review of an individual registered substitute chemical. The
development of testing methodologies and techniques, other related research
programs, and liaison activities with industry, academia, and other government
agencies are examples of these. Details of these projects will be provided
later in the program. These other activities and projects within the Alternative
Chemicals Program have been carefully evaluated, along with requirements
of the safety reviews, in order to obtain maximum program benefits within
the appropriated resources.
It is very difficult to establish a detailed safety review procedure which
can be applied across the board to every registered substitute chemical. The
type of pesticide, its use patterns, and the availability of scientific and
economic data are just some factors which influence the scope and resource
commitment of an individual review.
^Program Manager, Criteria and Evaluation Division, Office of Pesticide Programs,
U. S. Environmental Protection Agency
Preceding page blank 27
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What will be presented next is a general work-flow procedure which is
representative of the safety review of most registered substitute chemicals. This
procedure has been broken down into two phases in order to consider all possible
decision-making options that might arise during the review process.
Phase one of the review evaluates the safety of the substitute chemical
based on existing data bases. Phase two performs a detailed risk-benefit analy-
sis of present and projected uses of the substitute chemical (Figures 1 and 2).
Block 1 indicates the identification of those pesticides and their associated
problematic uses that require substitutes. These pesticides are identified from
pesticides that have been suspended, canceled, or in litigation, or during the latter
stages of the internal review being conducted in the C&E Division.
The second block identifies registered substitute chemicals for those poten-
tially problematic chemicals identified in block 1. At this point in the work flow,
those uses of a problem pesticide that have been canceled, suspended, or in inter-
nal review are listed. The EPA "Compendium of Registered Pesticides" is then
searched to determine which registered pesticides have one or more concurrent
substitute uses. A matrix of uses Is prepared and all of the registered substitutes
that have been registered for those particular uses are listed. In some cases we
may have a substitute chemical for several uses of a canceled product and in other
cases we may have a substitute for just one use.
These substitute chemicals are listed In order of priority for the review
process, and we begin the review processes on the first priority substitute pes-
ticide. Before starting a safety review of a registered substitute chemical, we
will notify by letter the manufacturer or manufacturers of that chemical of our
intent to review it. The letter will state as a minimum, an overview of the Alter-
native Chemicals Program, the uses that are registered as a substitute, and the
approximate time frame for this phase one of the review. These letters will be
going out very soon. I would expect by the end of next month.
28
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Figure 1
ALTERNATIVE CHEMICALS PROGRAM
Substitute Oumlcol R«v!«w - Phox I
to
to
NOTIFY
MANUFACTURERS
OF INTENT
TO REVIEW
—
SAFE USE
AS A
SUBSTITUTE
CONFIRMED
(SEE TEXT)
-------
Next the C&E Division review team will perform the initial scientific
review and mini-economic review of the substitute chemical. Dr. Axel rod has
touched on these reviews and they will be gone into in quite a bit of detail
in the afternoon session by Dr. Burkhalter and Mr. Conopask. They
essentially look at factors such as the chemistry, toxicology, pharmacology,
fate and significance in the environment, broad use patterns of the pesticide,
and the economic benefits of the pesticide to the user.
Upon completion of these two reviews, copies will be sent to the
manufacturers of the substitute chemical for their review and comment.
The manufacturer will not be under any obligation and will be asked to respond
strictly on a voluntary basis. Each manufacturer will have the option to
evaluate the data requirements and to supply additional data he might have
available which would assist us in the review process.
If the manufacturer desires, a meeting will be held at EPA to discuss
the safety review. This meeting will be scientific in nature. C&E will
have the members of the review team available to discuss the scientific
aspects of the review. No EPA policy or potential decisions on the suita-
bility of the substitute will be discussed at this meeting.
This brings us to the first key decision point in the program. At
this point in the review process we will have retrieved information from
all known existing data bases and from the manufacturer. Key C&E
scientific personnel will then evaluate the review to determine if this data
base is complete enough to make a decision with respect to the suitability
of the registered substitute chemical. If it is determined that additional data is
required, several sources will be contacted. If the data base is judged to be com-
plete, the safety review will continue to the next key decision point.
30
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The missing data for a review can now be clearly defined. If the missing
data is not obtainable from the manufacturer in a reasonable time frame, several
other sources will be utilized to fill these data gaps. Dependent upon the nature of
the missing data, EPA's Office of Research and Development (ORD) will be con-
tacted. ORD will play the major role in the effort to obtain missing data. Academia
through grants and contracts may also be contacted, as well as private contractors.
Now if there is a time delay in obtaining the missing data — that is, if it's
dependent upon a test method development or some long-range testing that has to
be done — the review team will go back to the use matrix derived in block 2 and
begin the initial review of the next pesticide in order of priority. I would like to
mention that there are several other research efforts already initiated by ORD
within the program that can be applied to the evaluation of all substitute chemicals.
Once the data has been obtained (if it's needed), we go to the next decision
point, which is safe use as a substitute confirmed. This is the second key decision
point in the work-flow chart for the review process. The issue here is, essentially,
in the viewpoint of key scientific personnel within C&E and ORD, have the initial
scientific and mini-economic reviews proven the suitability of the chemical to be an
acceptable substitute. If yes, EPA will place a statement to this effect in the
Federal Register. It will say compound X has been evaluated by EPA and found to
be an acceptable substitute for the canceled or suspended uses of the original com-
pound. *
If the answer to the safe use as a substitute cannot be confirmed, we
proceed one more time to the right on the flow chart and do not make any
public statements as to the relative safety of the substitute chemical. A
*Note: Since the Denver Symposium, OPP has reevaluated the issuance of this
notice and decided to delete it from the program. In its place C&E will recom-
mend to the Registration Division of OPP that a 5-year reregistration be granted
the pesticide under review and the manufacturer be notified once it is approved..
31
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detailed risk-benefit analysis will be performed next on the present and
projected uses of this particular substitute. This in effect initiates phase two
of the review process.
Perhaps before I go into phase two, if anybody has any quick questions
on phase one, I will be glad to answer them.
QUESTION: What impact or what relationship will this have to a cancellation
proceeding or a suspension proceeding which might be ongoing? Because the
first box Indicates that that would be going on. And what role would that play in
the cancellation proceeding or any other proceeding ?
MR. KENNETH OLSEN: Well, it would have impact in that if we found a
relatively safe substitute for the pesticide, that would be brought up during the
hearing. And, negatively, if we couldn't find any suitable substitutes, that might
have an impact on the future decision of the Agency.
QUESTION: But would the hearing go on independent to this program ?
MR. OLSEN: Yes. It's completely independent. It's carried out by the
Office of General Counsel of EPA.
QUESTION: What would happen in the event that the hearing determined
on its own, as has been done in the past, that there were substitutes available,
and their decision was to cancel the product, and your decision was contrary to
that or the reverse ?
MR. OLSEN: Well, we would maintain coordination with the hearing at
all times, and we would try to avoid this type of decision. During a litigation,
if certain substitutes were identified, we would attempt to answer the question
as to whether those substitutes are safer or more hazardous than the compound
that's in the hearing.
32
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MR, MEL GARBETT: What's the criteria for the order of priorities in the
selection of the substitutes ?
DR. AXELROD: The amount that one uses of the substitute, the number of
uses for the substitute and the specificity of or the exclusive use of a substitute,
and the economics of those uses would set up the matrix of the priority.
MR. ROBERT HAMMAN: I have a question concerning the Register notice.
Your review a compound which is registered on corn, for instance, and decide that
it is a good substitute. You publish this in the Federal Register. What happens if you
decide "no"? Does the Registration Division have to consider cancellation of that
product's use?
MR. OLSEN: No, that initiates the phase two of the review. No Register
notice will be placed If .ve say no. I'll get into that during the second phase of the
review.
We'll start here with the answer being no Federal Register being
placed (block 1). This initiates the comprehensive biosphere review of the
compound. We also perform a socioeconomic review which assesses the
net benefits and costs of the chemical at present and in the future. These
reviews will be discussed later in today's afternoon session by Drs. Dale
and Aspelin.
At tin completion of the biosphere and socioeconomic review, we
come to the third decision point, which is safe use as a substitute confirmed.
This is essentially the same block we had in the phase one review. Now
we have considerably more analysis and data to make that decision.
If the suitability of the substitute chemical can be confirmed at this
point, a Federal Register* notice will be published as before. If not, we
*Note: Since the Denver Symposium, OPP has reevaluated the issuance of this
notice and decided to delete if from the program. In its place C&E will recom-
mend to the Registration Division of OPP that a 5-year reregistration be granted
the pesticide under review and the manufacturer be notified once it is approved.
33
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Figure 2
ALTERNATIVE CHEMICALS PROGRAM
Substitute Chemical Review - Phase 2
CO
SAFE USE
AS A
SUBSTITUTE
CONFIRMED
NO
5-YEAR
REREGISTRATION
RECOMMENDATION
(SEE TEXT)
ISSUE BROUGHT
TO MANUFACTURER
AND EPA
OTHER
AVAILABLE
REGISTERED
SUBSTITUTE (S)
NO
-------
have to evaluate the results of the risk-benefit analysis that was performed.
This analysis is essentially forward looking with respect to the present and
projected future uses of the registered substitute chemical.
If the present use or uses of a registered substitute chemical present
certain problems with respect to safety, two parallel actions are initiated. (See
upper right area of Figure 2.)
The first of these is the identification of a problem with the present
use of the substitute. This problem is defined and communicated to the
manufacturer and other areas of EPA. OPP prepares a report based on
scientific data which outlines the potential problem strictly on a scientific
basis. Simultaneously, the use matrix that was prepared during phase one
is consulted and OPP initiates the review of an additional substitute, if one
is available.
If no other substitutes have been registered, two additional actions
are initiated. The first of these is a reevaluation of the original decision to
t
cancel, suspend, or impact the internal review of the original compound.
i
The second of these is to stimulate, through liaison efforts, the industrial
\
research by providing some sort tyf a need statement for a substitute chemical,
with respect to a particular use ol(a deregistered or suspended product.
If the risk-benefit analysis says essentially the present use of the
substitute is suitable, but indicat s out in the future you might have a
problem, two additional parallel/actions are initiated. (See lower right of
Figure 2.) The first of these lsjx> go back to the use matrix developed
during phase one, go to the nexj
the review process for this nexl
of the substitute chemical that 1
the identified potential problem
in the substitute role. This wil
time to correct this potential pi
substitute in order of priority, and begin
substitute. In addition, only the manufacturer
vS just been reviewed will be notified of
vith his particular pesticide when used
provide the manufacturer with some lead
blem before it occurs.
35
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That about concludes the phase two of the review. I have tried to
keep a few minutes for questions and answers. I've run through this maybe
a little fast in order to maintain schedule, but do we have any questions
on phase two or on the entire review process?
QUESTION: It's already been discussed and mentioned several times that
there were 70 substitutes for DDT. Now DDT has been canceled. It seems to
me that If this scheme Is going to be used, the first matter before the house
Is to review those 70.
DR. AXELROD: It's substitutes for a particular use that we're discussing.
It narrows down the field very, very considerably when you set up these reviews.
So, it isn't a matter that 70 compounds have been enunciated for all uses
simultaneously to DDT. It's a matter that DDT was so ubiquitously useful that
Into the marketplace came those already established or new ones, which for
some uses would be DDT substitutes. What we address there are those uses,
not a coverall for all uses.
QUESTION: Yes, but I think that the action against DDT was pretty much
for all uses.
MR. OLSEN: That's right, but the substitute chemical reviews are on a
use-by-use basis. They're not across-the-board reviews of all uses of DDT and
those substitutes that have been Identified.
QUESTION: I'm not quite sure whether this Is a question or a statement.
But If you will publish all of the substitutes that are available, as you said, is
this not just a restatement of the registration process, which states that these
uses have been examined and found capable of being registered.
36
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DR. KORP: I agree with you. But, as pointed out, once you have given
this a special blessing because it's gone through a review process, everybody
doesn't know about all those that are registered that might be desirable. I don't
know what will happen yet. It might be desirable to show that there are these
compounds plus others available for this particular use.
37
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OFFICE OF PESTICIDE PROGRAMS LIAISON
Frederick W. Whittemore, Ph.D.*
In the few minutes which I have this morning, I would like to talk to you
for just a short time about the functions and responsibilities of the Operations
Division and how they relate to the Alternative Chemicals Program. The Opera-
tions Division is responsible for the development of programs designed to enhance
the effectiveness of government activities in the pesticide area. In carrying out
these responsibilities, it provides program policy direction to the technical assis-
tance and training programs and to the gathering of Information on the consequences
of pesticides use. And It Is in this particular area that we have a direct relation-
ship to the Alternative Chemicals Program.
Of particular import in these responsibilities is the outreach aspect, which
provides EPA with liaison outside of Its headquarters structure at two levels,
national and state. In dealing with the various responsibilities of the Operations
Division, we have chosen to organize it into two branches. One, a liaison and
training branch, and the other a pesticides use consequences branch.
It is important to recognize that although EPA is responsible for the admin-
istration of FIFRA, the Agency is only one facet of a rather complicated national
system of pesticide use and management. The Agency has the dual and sometimes
conflicting role of assuring maximum safety and environmental integrity while
being responsible for maintaining workable processes of registration, regulation,
and enforcement which provide the public with needed chemicals and associated
devices.
The ten regional offices provide a national network which facilitates the
process at the state level. First, at the national level, the Operations Division
is responsible for maintaining coordination with a number of Federal agencies,
*Acting Director, Operations Division, Office of Pesticide Programs, U. S.
Environmental Protection Agency
39
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most particularly with the U. S. Department of Agriculture. In accom-
plishing this coordination effort, we actively participate and support the Secre-
tariat of the Federal Working Group on Pest Managment and have EPA represen-
tation on the appropriate panels of that working group. (Panels have to do with
such subjects as monitoring, research, categorization, training, things of this
type.) We also have within our division, a Federal Agency Liaison Officer who
has direct responsibility to maintain liaison with these other Federal agencies.
On an ad hoc day-to-day basis we, of course, have very close liaison with
Agriculture, the Agriculture Research Service of Agriculture, the Extension Ser-
vice, and the Forest Service.
A typical example of our liaison activities with, for example, the Extension
Service, is a recent decision by the Administrator of EPA, Mr. Train, and the
Secretary of Agriculture, Mr. Butz, to seek supplementary funding for the training
and certification of pesticide applicators required for the implementation of FIFRA
by the rather magic date of October of 1976, by which time state programs for the
certification of applicators must be in place and applicators must be certified if
they are to use restricted-use pesticides.
With respect to headquarters liaison with national organizations and pro-
grams, we again have a number of national organizations in which we actively par-
ticipate and have representation. The first of these is the National Association of
State Departments of Agriculture. In the last 6 weeks, Dr. Osmun has attended
four regional meetings of this organization to explain the implications of section 4
and the legal authorities that states must have to license and certify applicators.
We have also had meetings with the American Association of Pesticide
Control Officials. These are representatives of the state agencies responsible
for the regulation of pesticides within the states. In addition, we have had a num-
ber of interchanges with respect to OPP and EPA responsibilities in the area of
40
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pest management strategies, and the Office has sponsored one project in California
on the integrated pest management of production tomatoes. There are also other
national organizations with which we have very strong and close contacts, such
as the National Aerial Applicators Association and the National Pest Control
Association.
With respect to liaison at the state levels via the regions, EPA has ten
regions throughout the country and our contacts with the states are via those
regions. In each one of the regions we have a Pesticides Branch Chief. Certainly
with the implementation of FIFRA and especially with the implementation of sec-
tion 4 and the program for state certification of applicators, it will be essential
to involve the regions in this program.
I mentioned earlier that we have within the division a liaison and training
branch, and the activities which I have been discussing up to now have been specifi-
cally related to that branch. In addition, we have a pesticides use consequences
branch, and within that branch we operate what is known as PASS, the Pesticide
Accident Surveillance System.
This activity, of course, involves recording accidents as they occur and
assembling data on accidents with the view of establishing or identifying major
problems and, hopefully, coming up with suggested solutions to those problems
as they may relate to packaging, formulation, and registration.
Of even greater importance, however, are other activities of this branch
which, quite frankly, have not yet been fully defined. These have to do with the
subtle, currently unrecognized events that may be taking place as a consequence
of pesticide use. If we knew all of the devils that there were in all of the pesti-
cides with which we are dealing, our problem would be simple. But the fact
remains that some of the compounds about which we know the most — and, I'm
referring here specifically to DDT — have virtually passed from the scene.
41
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We have a long use experience with DDT and some of these other older
compounds. Our use experience with some of the more recent compounds is very
limited, and possibly there are many hidden devils in these newer compounds
which are completely unrecognized at this particular point in time. This to me
Is a very Important aspect of the results of the consequences and the changing
patterns of pesticide use.
It Is In this area, I think, that we have a very close relationship with the
Substitute Chemicals Program, because certainly some of the chemicals which
can be considered as substitutes do not have the long history of use either In
this country or abroad by which such problems can be Identified. We may have
many unrecognized problems with some of these so-called substitute chemicals.
In summary, the Operations Division has two main functions: First,
liaison and training, with particular reference at the moment to the training and
certification of pesticide applicators to comply with the provisions of the new
FTFRA. Secondly, pesticide use consequences, with current emphasis on what
we call the Pesticide Accident Surveillance System. I would hope longer-term
emphasis would be upon the consequences of pesticide use and some of the unrecog-
nized hazards which undoubtedly still exist In some of the new compounds.
QUESTION: Perhaps I misunderstood some of the things that you were
saying, but It seems to me that one of the thrusts of what you said was that In
the exploration of the substitutes, it would be important to look for hidden problems
that may exist with some of the substitutes, If not all. Is this not contrary to
the program as Dr. Axelrod described It? I struggle everyday to look for a
positive attitude. This one's a little confusing.
42
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DR. FREDERICK WHITTEMORE: Well, if we could identify the devils, they
wouldn't be unknown. But I am firmly convinced, having had some experience in
this, possibly for 35 years, that the devils that we know are better than the devils
we don't know. Because, if we know the devils, we can identify them and we can
cope with them. After all, I have been in this work ever since 1941 and was
probably one of the first ones to use DDT on a broad scale in North Africa and
in Naples in 1943.
And I keep going back to the proposition that if we know the devils, we can
recognize them and we can contend with them. It's the devils we don't know that
are hidden in these compounds that we really should start worrying about.
I can recall it wasn't too long ago when people didn't worry about residues
of parathion. We thought that parathion residues more or less disappeared.
It wasn't until maybe 4 or 5 years ago that we recognized that maybe residues
of parathion on food commodities would be a problem for as long as 30 to 45
days after application. And I repeat again, if we know the devils and we can
recognize their magnitude, we can deal with them. It's the unknown devils that
we should worry about in certain instances.
MR. ALFRED MITLEHNER: In line with what you're saying, is it reasonable
to suggest that the modification of a use pattern of a suspect chemical might
indeed be the best alternative to that particular situation and that this should be
a part of the Alternative Chemicals Program, in addition to looking for different
chemicals ?
DR. AXELROD: I guess we can speak from present experience in the C&E
Division, where internal reviews of suspect chemicals are being conducted-,
that indeed we're not looking across the board. Hopefully, not to make the kind
of errors we have in the past been accused of with DDT, but looking separately
at the various uses. And I think that we're getting a better appreciation for that
separate look at certain uses, which might mean further work on the part of the
43
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Agency but not across the board. That modification of use patterns might indeed
be one way to go to remove the substitute or suspect chemical from that suspicion.
But I'd like to give much more thought to that.
DR. JERRY SMITH: Would not a rational, non-abrupt alteration in the
use pattern of a pesticide suspect of being hazardous, bring in competition? Would
not free enterprise provide the alternate or substitute chemical ? That is, as we
gradually withdraw a pesticide from use, will not new registrations themselves
take care of the problem ?
DR. KORP: The problem you face is that you tell us 7 years and $10 million.
In other words, I don't want to have a 7-year hiatus. In other words, at least
we ought to be looking. I mean, I don't disagree with you; I'm just saying that
it isn't something that you can snap your fingers and have something fill in.
So if we look, we're just simply trying to accelerate the process.
DR. SMITH: What we're trying to do is to prevent the abrupt removal of
a pesticide from the market, leaving a void. If something has been on the market
for years and years, you don't all of a sudden... ,
DR. KORP: No, I won't accept that statement. That's not a fair statement —
the fact that something got on the market, in other words, erroneously. You'll
have to remember that we have new knowledge, new opinions, and new everything.
In other words, we've got to look at these things based on the current situation,
not what it was back in 1908.
DR. R.E. HANSON: I think the question's directed toward Ken, but there
is a point in there where there's a meeting with a manufacturer. Now let's take
a proprietary compound, and for whatever reason we disagree with your assess-
ment of a substitute and we say no way will we have anything to do with registration
«•
of that product as a substitute. What happens to the Substitute Chemicals Program
then?
44
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MR. OLSEN: The meeting will be held on already registered substitutes.
We're evaluating a registered substitute, not a new compound.
DR. HANSON: No, I'm talking about an old compound, but not registered
for that use.
MR. OLSEN: Well, it will be registered for the use and that would be a
viable substitute.
DR. HANSON: So, you will not be looking at a non-registered compound.
MR. OLSEN: That's right.
DR. HANSON: Somewhere in that chain of events though, when I unravel
what all those charts mean, there must be that too.
MR. OLSEN: Right. Well, that's toward the end of the review where we
identify that no substitute is available.
DR. HANSON: No registered substitutes.
MR. OLSEN: No registered substitutes. First, we look at all the
registered substitutes by use.
45
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INITIAL SCIENTIFIC REVIEW
Thomas D. Burkhalter, Ph. D. *
The initial scientific reviews present general discussions on potential
human and environmental safety considerations of registered alternatives for
uses of a pesticide that have been suspended, canceled, or are described as
being suspect.
The scientifically oriented review relates to broad methods of pesticide
applications and includes all uses of the product (Figure 1). The objectives of
the review are mainly two-fold, whether conducted on alternatives for canceled
use or on alternatives for a suspect use product (Figure 2). These objectives
are to analyze the safety factors for the substitutes as a basis for a decision to
proceed with a more comprehensive biosphere review and, secondly, to describe
areas in which technical data are lacking so that appropriate studies can be
initiated to develop definitive Information.
Figure 1
Initial Scientific Reviews
Purpose;
1. Review safety aspects of registered substitutes
for canceled pesticide uses.
2. Review safety aspects of registered substitutes
for suspect pesticides.
*Head, Plant Physiology Section, Plant Studies Branch, Criteria and
Evaluation Division, U.S. Environmental Protection Agency
47
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Figure 2
Initial Scientific Reviews
Objectives;
1. Determine need for further reviews.
2. Define knowledge gaps.
«
The initial scientific reviews are conducted by multidisciplinary teams
comprised of scientists in the field of chemistry, toxicology, wildlife biology,
ecology, and disciplines to which the pesticide uses belong, such as entomology,
plant pathology, and physiology (Figure 3).
Figure 3
Initial Scientific Reviews
Scope:
1. Multidisciplinary teams
2. Chemistry, use methods, and toxicity
Presently, insecticide and herbicide teams are preparing to review
registered alternatives for the canceled uses of DDT and 2,4,5-T. If the
initial scientific review is for an alternative pesticide use substituting for a can-
celed use, the factors may be considered to center on those relating to the
reasons for cancellation: This could be persistence, toxicology, or bloaccum-
ulation. If the review is for uses of alternative pesticides for a suspect
product, the subtitute's safety is to be verified. „
The data to be reviewed relate predominantly to chemistry, use, and
toxicity, Which are interpreted according to the character and method of the
use of the product.
48
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The initial review for chemistry involves four major categories involv-
ing phyBiochemical properties, analytical methodology, residues for food and
feed, and, of course, the environmental aspects (Figure 4). Physiochemical
properties include those areas in which, for example, synthesis and production
technology are considered in terms of intermediates, wastes, and side reactions
which may pose adverse effects.
Figure 4
Initial Scientific Reviews
Chemistry;
!„ Physiochemical properties
2. Analytical methodology
3o Residues in food and feed
4. Environmental
Secondly, the composition of the technical and the formulation is con-
sidered. Physical properties, such as melting point, boiling point, specific
gravity, vapor pressure, and partical size are under consideration as well as
chemical properties and reaction, such as degradation reactions and chemistry
of metabolities, decomposition reactions and processes, hydrolysis, thermal
decomposition, photalysis reactions, pH and stability, and oxidation reactions.
The analytical methodology is concerned with acceptable methods in-
volving reproducibility and sensitivity, and for regulatory purposes satisfies
enforcement needs. Methods are evaluated not only for the active chemical,
but also for the principle degradation products, as delineated in the above pro-
cesses. These are to Include analytical procedures for food and feed crops,
water, soil, and biological entitles.
49
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The method should have specificity to pick out the chemical or degradation
product from mixtures. Analysis of pesticides in corn, for example, may yield
several pesticide chemical entities used on the crop. Each chemical should be
distinguishable from the other.
In terms of residues in food and feed, considerations on residues involve
several distinct areas: the occurrence of pesticides in food and feed crops; the
relationship of residues in food tolerances established and food tolerances pend-
ing; the relationship to acceptable daily intake; and the results of monitoring
programs, including FDA market basket study and the USDA consumer and
marketing studies.
Environmental considerations are, of course, always paramount. The
fate, movement, and transport of pesticides in the environment is a focus of
many concerns. This involves a potential for secondary effects particularly on
the non-target areas resulting from the chemical or its important and toxic
metabolites. These areas include persistence and toxicity of the chemical and
its metabolites, leaching of the chemical or the toxic metabolites out of the
target area, bioconcentration in a species, and bioaccumulation of the chemical
or its metabolites through the food chain.
The toxicity evaluation of a pesticide cannot be underestimated and is
intended to include toxicology, pharmacodynamics, species behavior, records,
and potentials (Figure 5). For toxicology and pharmacodynamics, the first
information one thinks of is the toxicology of acute, subacute, and chronic
effects. These normally involve toxicity to laboratory animals and to domestic
animals. Toxicology efforts are not limited to these and continue in sympto-
mology, pathology associated with animals, toxicity to fish, toxicity to other
aquatic species, toxicity to wildlife, and metabolism including absorption,
distribution, excretion, and biotransformation.
50
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Figure 5
Initial Scientific Reviews
Toxlclty:
1. Toxicology and pharmacology
2. Species behavior
3. Records and potentials
Also, the genie effects are carcinogenic effects, tratogenic, mutagenic,
and tumorogenic effects. Species behavior is considered In effects on repro-
/ ductlon In laboratory animals, domestic avian species, and crustaceans, and,
/' of course, in behavioral effects.
Records and potentials include such things as field exposure evaluations,
ecological imbalance effects, and Incident records.
Use aspects are always important and they include, generally, application
rates, patterns of use, methods and applications of timing, drift, exposure, and
form in which it is applied as in EC or dust or granule (Figure 6). The develop-
ment of use aspects of a pesticide Involves first a collection of the registration
history. This Includes Federal Registration, state cancellation and suspension
actions, and the highly informative state recommendations, which reflect commonly
recognized practices.
Figure 6
Initial Scientific Reviews
Use Aspects;
1. Application rates and use patterns
2. Application methods and timing
3. Formulation in which applied
51
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The collected information provides a record of label and labeling for each
use, which acts as a basic source for all use aspects and generally includes
these points: currently registered uses both on cropland and on non-cropland,
including previously registered uses which have been dropped by the sponsor,
canceled, or suspended; dosage rates currently accepted by the registration
division (this may also reflect those instances in which recommended dosages
of an established product have been increased or decreased at the request either
of the sponsor or of the Agency); formulation including the form in which a pro-
duct is available for each use and dosage, such as wettable powders, granules,
dusts, emulsifiable concentrates, flowable suspensions, and so forth; the
frequency of application, the number and time between applications; timing of
the application, including dormant, prepliant, preemergence, and so forth;
specific application directions and techniques such as soil incorporation, sub-
surface metering into irrigation water, or air application.
Of critical Importance are the label directions and limitations designed
to further assure safe, effective use. These include preharvest intervals,
rotational cautions, geographic restrictions, and land use limitations.
Other information is also collected which impinges on the use but is not
necessarily reflected in the labeling. State, regional, and more local actions
to restrict or deny use of a particular pesticide are considered. Actions at the
state and local levels to promote and recommend, particularly for uses not
Federally registered, are also considered.
Information on all these aspects surrounding the use of the pesticide is
obtained from a variety of sources. Some of the most important are Technical
• '%
Services Division data base arid bibliographies, EPA registration files, Federal
*
and state research stations, pesticide manufacturers, trade associations, and
scientific literature.
52
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On completion and evaluation of the initial scientific review, each regis-
tered use of an alternative for a suspect or canceled pesticide is examined in
terms of the data assembled (Figure 7). The team leaders may elect to use
consultants. One of the following courses of action is then taken for each
alternative pesticide, as described this morning by Mr. Olsen.
Figure 7
Initial Scientific Reviews
Actions;
1. Safety confirmed
2. Insufficient data for decision
3. Safety questionable
When the safely is confirmed, this decision concludes that an alternative
pesticide use reviewed for safety may be considered an acceptable substitute for
the canceled or suspect pesticide use. The decision, therefore, verifies that
the alternative is acceptable as intended.
There is, of course, an interim decision when there is insufficient data
to decide. Significant data gaps are defined and appropriate investigations
initiated to determine if the information in the normal registration process or
unpublished data exists to fulfill these gaps. If not, research needs will be
delineated, as well as input from other sources, as indicated this morning by
Mr. Olsen.
The third decision is the decision of questionable safety. This decision
initiates a comprehensive biosphere and socioeconomic review of the substitute
pesticide use. This aspect of the review will be described later on this afternoon.
53
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THE MINI-ECONOMIC REVIEW
Jeff Conopask*
In assessing the substltutability of a chemical for those registered pesti-
cides for which adverse legal action has been taken by the Agency, it is most
important to analyze the basic economics at the user level. Such questions as
the following will be asked: Are there economic substitutes ? Will the chemical
production industry be able to produce substitutes in adequate quantities as
demand increases for these chemicals ?
The purpose of the mini-economic review is to provide an initial assess-
ment of these questions. The approach is to consider both the supply and demand
sides. A more detailed analysis may be required later, if significant environ-
mental problems are found to exist from the initial scientific review.
On the supply side, the basic concern will be whether or not the industrial
capacity of producing a substitute chemical is commensurate with a potential
demand for that chemical. Figure 1 shows that we need a number of data points
to analyze this aspect. They include the following: total production level for both
the current year and the previous 5 years; the number of firms in the industry
producing this particular chemical, and their aggregate capacity; the exports and
Imports involved with the chemical; and formulators and distributors of the chemi-
cal.
The International nature of the problem has become crucial in recent
months, since the international export market has been much stronger than the
domestic market. The relaxation of price controls earlier this year has helped
to alleviate this price situation somewhat, but producers can sometimes obtain
better prices overseas for many of their pesticide products than they can domes-
tically. With expanding world food production, this could pose a serious problem
to selected substitute chemicals experiencing increased domestic demand as well.
*Economist, Economic Analysis Branch, Criteria and Evaluation Division,
Office of Pesticide Programs, U.S. Environmental Protection Agency
55
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Figure 1
Mini-Economic Review Procedural Outline
en
at
I. Introduction
A. Identification of chemical and nature
(i.e., name; systemic)
B. Broad use categories
II. Supply
A. Domestic
1. Production
a. current
b. recent five years
c. number producing firms
d. industry capacity (aggregate)
2. Distribution
a. number formulators and
distributors
b. location of same
B. International
1. Imports — volume, trend
2. Exports — volume, trend
III. Demand
A. Identify specific uses — agricultural
1. Crop/pest combinations
2. Geographic restrictions
B. Usage
1. Quantified by crop/areas (regional, state)/years
2. Acreages by crop/areas (regional, state)/years
3. Identification of percentage of nationally
pesticide treated crop
C. Non-agricultural uses
1. Use, area
2. Quantity, area
D. Efficacy and cost effectiveness (Agricultural)
1. Physical effectiveness of alternative chemical
a. indicators of control relative to check
plot
b. time frame of application
2. Physical yield response
3. Assess benefits and costs
a. assign technical material and application
cost
b. value of yield response vs. check plot
yield with 3 year average crop price
calculate gross benefit
IV.
c.
Conclusions
-------
In conjunction with the supply problem, the availability of feed stocks for
pesticide producers may well continue to be a critical issue. With this in mind,
the Economic Analysis Branch is expanding its expertise in assessing developments
affecting supply and demand for pesticides as part of its overall responsiveness to
the needs of the Criteria and Evaluation Division (C&E) of the Office of Pesticide
Programs (OPP). We are in the process of data collecting, trade news monitoring,
and generally conducting literature searches to assess the current and future supply-
demand situation for pesticides.
Data sources to satisfy the entire supply section include U. S. Tariff Com-
mission Annual Reports, U. S. Commerce Department Annual Reports, the Depart-
ment of Agriculture reports, plus various agrichemical trade publications and
sources. I might add that we have a fairly good working relationship with the
relevant subbranches in these government agencies, and we are able to get at
some of the disaggregated data.
On the demand side, this section can be divided into two general areas,
namely use patterns and efficacj plus cost effectiveness. The first component is
the descriptive analysis. All rf/gistered uses of the substitute pesticide will be
considered. Data on quantities/consumed are required to ascertain the pattern
of chemical use and how it is e
olvlng. This is required since many substitute
chemicals are more target specific than the wider-spectrum pesticides they are
replacing.
Information require/, for this includes the quantities consumed in pounds by
use and area. For agr leu jure this would mean crop by region or state, if possible,
plus the delineation of tre/ted acreages by crop, region, or state. The Information
Is needed for at least two points in time and preferably three to evaluate trends In
the use patterns. This v|.ll indicate a replacement pattern for those chemicals
which have been subject o adverse legal action by the Agency.
57
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The other component concerned with efficacy and effectiveness is a design
to further document the effectiveness of the chemical and Its various uses, both
major and minor. This is based upon available results of tests and literature.
In the mini-economic review, the chemical is evaluated entirely without regard
to other considerations. Later, under the Alternative Chemicals Program, detailed
comparisons of performance can be made with specific chemicals subject to past
cancellation in order to determine impacts on users and consumers.
So far, we have not included such comparisons In the mini-economic
reviews, and a further delineation of this will be given by Dr. Aspelin in a few
minutes.
The efficacy assessment step will be to evaluate the pest-controlling
strength of the alternative in b. pest body count sense or a percent disease con-
trol sense. This also Involves consideration of a defined time frame of applica-
tion and the length of time various levels of control are effected. Next, user
costs are considered. The substitute chemical may require more pounds of
technical material and may cost more to achieve some level of control relative
to a canceled chemical. Again, we are looking at these chemical costs by them-
selves, however.
It is Important to get a handle on increased cost of application to the
farmer. The agricultural sector has a demand curve which Is inelastic so that
the farmer is essentially a price taker; he alone with his crop cannot affect price
when he brings it to the market. He cannot readily pass on Increased cost In pro-
ducing his goods, unless, of course, we have a situation that has developed In
recent years — well, the last 2 years to be more specific — In which the results
of an exceptionally strong demand for more and higher quality foodstuffs both here
and abroad have resulted. This strong demand has allowed farm operators to
pass some of their increased costs along In the market, but history demonstrates
has been a unique experience and the future frequency of this Is uncertain.
-------
Data requirements here are rather simple. We need the cost of technical
material plus a specialized application cost. If the pesticide is applied concurrently
with the seed at planting or with the fertilizer application, it has been our approach
that the application or placement cost is considered infinitely small and of little
consequence to the analysis.
The last step brings together the first two in an assessment of gross bene-
fits. Analyzing percentage kill data is not enough. It is only part of the pest control
strategy of a user, since economic returns are his goal. We need to know the effect
on yields and to translate that into evaluation of the product increase.
For example, we may have two test plots, one treated with the alternative
chemical and one untreated. The positive difference of the former over the latter
would be the yield increrse; taking a recent 3-year average price of the crop in
question and multiplying it times the unit of measure would give the gross benefits
unadjusted for application costs.
The data sources for the yield response are EPA registration file data,
state experiment station results, or other studies. The evaluation of the yield
response is then compared to the cost of application, which will give a gross
benefit as shown in Figure 2.
Figure 2
Gross Benefit Calculation
Value of Increased Yield From Treated Crop
— Material and Application Cost
Gross Benefit
This demonstrates the substitute's effectiveness as an alternative to a
chemical which has suffered adverse legal action from the agency.
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This empirical conclusion then answers the question: Is there an economic
substitute or substitutes, as the case may be, for a chemical which has suffered
adverse legal action by the Agency ? This Is a yes or no question with no preference
ranking of any of these substitutes. Whenever possible, as far as data limitations
are concerned, this will be done on as many specific target crop pest combinations
as possible.
The preceding works best for agricultural uses, but for industrial and urban
uses it presents both conceptual and empirical problems. As an example, how do
you measure the benefits of brush-free rlghts-of-way to the user? In the case of
electric utilities, one of the major uses, it would simplify maintenance of electric
transmission tines and noninterference from trees and brush.
How do you quantify these benefits ? In those cases in. which the benefits
are nebulous and hard to define and quantify, we have suggested to our contractors
and our in-house personnel to utilize an alternative costing strategy which considers
non-chemical control. For uses such as home fly control, how do you quantify the
probabl reduced health and nuisance costs, plus the obvious aesthetic benefits of
not having flies buzzing around the home ?
The alternative costing technique is viewed, then, as the best possibility
of offering some economic input to the research process for these areas.
In conclusion, we would like to stress the initial first-cut nature of the mini-
economic review. In many cases we are in a data-short position with respect to
use changes in the last few years. Although three USDA nationwide use pattern
surveys have been published, there is little available data on nationwide use changes
since 1971. Efficacy data and yield response data are limited, especially the latter.
One of our major tasks In the mini-economic review is locating new sources of data
as well as Interpreting existing sources.
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BIOSPHERE REVIEW
Lamar B. Dale, Jr., Ph.D.*
The biosphere includes all living organisms interacting with the earth's
abiotic environment. It includes all ecosystems, which interact within and among
themselves to maintain steady state in both the flow of energy and the cycling of
nutrients. The complex interactions which lead to this transfer of energy and
nutrients provide for the opportunity of the transfer of toxic materials, such as
pesticides and their metabolites.
Pesticides are dispersed in the air, water, soil, and moving organisms
and can eventually be found far from their original source of introduction. Two
types of impacts on the biosphere may result from this dispersion. One is the
adverse impact on specific birds, fish, and insects that are vulnerable to pesti-
cides and their metabolites. The second is a potential vulnerability to ecological
processes as fundamental as photosynthesis in the oceans.
To assess these impacts, the biosphere review will entail a similar
scrutiny of the literature previously cited for the initial scientific review. How-
ever, the detail and comprehensiveness of this review requires a total evaluation
in quantitative terms, whenever possible, of the potential hazards of the use of the
pesticide in question. An in-depth review of the current literature and consultation
with experts in the pesticides research field will be required to compile this infor-
mation concerning the current pesticide research by individuals and private academic
Institutions.
Before we continue, let me emphasize a point that came up several times
this morning, that EPA not only has the responsibility of ascertaining that a pesti-
cide does not produce an unwarranted adverse effect on the environment, but also
has the equally important responsibility of not sacrificing a good, economically
important pesticide without just cause.
*Branch Chief, Metabolic Effects Branch, Office of Pesticide Programs, U.S.
Environmental Protection Agency
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Unlike the chemicals reviewed in the internal reviews carried out by
EPA in the past and present, the pesticides that will comprise the alternative
chemicals list will be selected because they are considered to be effective
for certain uses of canceled pesticides. And, more Importantly, they have
been selected because they have been considered to be safer for the uses in
question than a canceled pesticide.
The purpose, therefore, of the initial scientific review, as presented
by Dr. Burkhalter, is to confirm this original appraisal. However, if the initial
scientific review uncovers evidence that may cast doubt on the safety of the alter-
native pesticide, a biosphere review is Initiated.
In this review, the area or areas of question will be studied in depth.
In carrying out this review, we will not only utilize data studied in the initial
scientific review, but also utilize data from studies in progress, utilize new tech-
niques of data analysis in order to obtain full meaning from these data, initiate the
development of new test methods which will yield more meaningful data, make
in-depth studies of the exposures resulting from the use or uses involved, and
only then determine if the risk is real.
If the risk is not real, we will have concrete evidence that the pesticide
Is a true alternative for the use in question, and we will be able to defend this position.
If the risk is real, the risk will be weighed against the benefits derived from
the pesticide as determined in the socioeconomic review which Dr. Aspelin will
cover.
By necessity, each biosphere review is unique unto itself. We will not
know the problems we will be studying until they arise. Each review will
present its own problems and the design of each study will be dependent upon these
problems. Therefore, at this time, I can only speak in broad generalities and tell
you what we envision.
I am going to address a number of areas of concern. Certainly, I do not
have expertise in all of these areas. However, in addition to the Criteria and
Evaluation staff, we do plan to utilize both industrial and academic experts and
consultants to assist us with this difficult task.
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I will attempt to answer three questions: Just what a biosphere review
is, how we carry it out, and why we carry it out. I have already briefly touched
on the answers to all of these questions. I will try to go a little deeper, or as
deep as I can at this time, Into the answers.
Just what is a biosphere review? Certainly, from the name it sounds
as if we intend to study life itself, but actually, the study is not quite that ambitious.
First, the review consists of an in-depth study of the area or areas of
concern ad indicated by the initial scientific review. Secondly, the biosphere
review attempts to relate any real question of safety uncovered to possible effects
to man and the environment which may result from the use of the pesticide. In
other words, we are taking the position that it is not enough to demonstrate that
this pesticide in high doses produces an effect in a test tube or in laboratory
animals; we will try to make an estimate of the meaning of this in real terms of
human exposure.
The initial scientific review can be considered as taking a thin horizontal
slice across the biosphere as follows (Figure 1). This includes the available
scientific data on chemistry residues, toxicology, wildlife effects, fate in the
environment, and patterns of use.
Figure 1
Initial .Scientific Review
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In the biosphere review (Figure 2) we take a continuous slice through
the biosphere and attempt to relate each slice one with the other in order to
determine how one area affects other areas of concern.
Figure 2
Biosphere Review
Effects
Pesticide
Released
Pathways
Population
Exposed
\
Use
Patterns
j
Risk
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If In the initial scientific review (Figure 3) we uncover a question of
safety in one of the areas of concern, we will first study that question area in
depth.
Figure 3
Biosphere Review
1. Rereview of the study or studies in question
a. Exat.iination of raw data (and tissues) if available.
b. Determination of suitability of species utilized.
c. Subject data to other techniques of analysis.
2. Search for and evaluate other studies, unpublished or
in progress, and
3. If necessary, design and carry out studies which yield
necessary data.
4. Utilize these data in assessment of exposure effects.
For example, this may be a chronic toxlclty. The first thing we will
do Is review the question study In depth. How do we do this? The first possible
step is to reexamine the raw data and the tissues involved, if they are still
available, and to submit these tissues and these data not only to our rerevlew
but also bring in consultants for their opinions of these data.
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In this we may determine if the species of animal utilized was the best
species to demonstrate this effect and if the best analytical technique and the best
statistical treatment were utilized. If not, we will try other techniques.
The second step Is to search for other studies In progress or other
studies which have not been reported. This we can do through the manufacturer
himself, through academic institutions, and through research going on In the govern-
ment. Then we can assess these data, if this Is not enough, we can design and
carry out other studies that would yield the data required to make a decision. Finally,
after all of these steps have been taken, we will utilize these data in the assessment
of the possible exposure effects resulting from the use of the pesticides.
The next step In the evaluation of the pesticide use Is to determine the
quantity of pesticide released Into the environment (Figure 4). This release may be in
the form of a controlled local release or an accidental or Industrial loss. This will
depend mainly on historical data obtained from industrial and governmental agencies.
Figure 4
Biosphere Review
1. Evaluate quantity of pesticide released into the environment.
2. Determine pathways of migration of pesticides.
3. Determine exposure resulting from use patterns.
4. Determine exposure/effect relationship between each use and
health of man.
5. Estimate present and projected populations at risk.
6. Use estimates in conjunction with data developed in Socio-Economic
Review to make benefit/risk analysis.
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The release due to accidents will be difficult to predict, as scanty historical
data exists. However, by resorting to data available in related fields of hazardous
material, we will make transport and production estimates of expected release of
pesticides due to accidents in industrial and transportation operations.
Once the current and projected release of a pesticide is known, we will
determine its migration patterns in air, land, and waterways, as may be appropriate.
We will track the most significant pathways by identifying organisms and their
interactions which comprise transfer mechanisms. By estimating the amount of
pesticide or metabolites lost or accumulated in each transfer, we can assess
the level of exposure to vulnerable organisms or ecological processes. In
addition, use patterns, formulations applied, and established agricultural
practices will be examined in detail to determine human exposure as a result
of application of the pesticide.
Having established migration pathways of the pesticide and exposure
resulting from its application, we will determine the exposure effect relationship
for man, animals, plants, and ecological systems identified as being vulnerable in
the above study.
Assessments of possible effects will be obtained from the pharmacological
and toxicological data reviewed and/or developed in this study. Based on all
information developed in the study, we will estimate the present and projected populations
that are jeopardized by a particular pesticide use and the degree of risk involved.
The information developed In this study will be utilized in conjunction with
the data developed in the socioeconomic review to make a benefit-risk analysis
for each pesticide use. This is a very ambitious undertaking, and, as I said in the
beginning, all of these steps will certainly not be required in each case in which a
problem is uncovered.
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THE SOCIOECONOMIC REVIEW
Arnold L. Aspelin, Ph. D. *
I am most pleased to share with members of agriculture, industry,
and academia some of our current plans for socloeconomic analysis in support
of EPA's Alternative Chemicals Program. It is a distinct pleasure and a
challenge as an economist to be a part of the Alternative Chemicals Program
and to be here to discuss the role of socioeconomic studies in it.
As we saw this morning, the needs for data on economic and social
values are great. While this is true, economists and other social scientists
are newcomers to the analysis of pesticide matters, compared to our friends
in the physical and life sciences.
What is a socioeconomic review? In general, it is a scientific review
of the economic and social consequences of the use of a pesticide for purposes of
contributing to the data base for determination by the Administrator as to whether
the benefits of use justify the risks to be taken in the case of a pesticide which has
been proven to generate risks if used as an alternative to a pesticide subject to past
or prospective adverse regulatory action. The focus of this socioeconomic review
is the expanded use of the pesticide as an alternative — not its regular, present use.
As Dr. Korp noted this morning, there are no easy, magic formulas
to answer this question. Consideration of social and economic values in pesticide
regulatory matters is mandated in FIFRA as amended in 1972 in the definition
of unreasonable adverse effects on the environment, which is the prime criterion
for decision-making under this law. it is defined to include any "unreasonable
risks to man or the environment, taking into account the economic, social, and
environmental costs and benefits of the use of any pesticide. "
Detailed socioeconomic studies which cover the several areas cited
in the above definition are undertaken only in instances in which there are some
*Chlef, Economic Analysis Branch, Criteria and Evaluation Division, Office of
Pesticide Programs, U.S. Environmental Protection Agency
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real or proven risks to man or the environment due to the expanded use of
the alternative which could conceivably be justified on the basis of social and
economic benefits. In such a case, economists and other social scientists
conduct studies in a multidiscipllnary mode, interfacing with the physical and
life scientists who conducted the biosphere review.
One is struck with the scope of the definition of "unreasonable adverse
effects" on the environment, bringing with it the possibilities for excessive amounts
of analysis leading to a burden on program resources and a lack of timely
decisions under the program. But this will not be the case. As you would
expect, the analysis of social and economic values is being implemented in
OPP without an excessive budget.
Let me hasten to say that it is not without an adequate budget. With
the possible exception that we need many critical data that are not presently in
our hands in order to achieve our task, there are many critical data needs
which require further exploration by all groups interested in regulatory matters.
Let me make one more observation before turning to the components of
a socioeconomic analysis. The concept of "unreasonable adverse effects" is not
a precise term. It provides for flexibility under changing economic conditions
and national priorities such as has been necessary during the energy crisis
and recent pressure on food supplies.
A unit of environmental protection is much more expensive today than it
was a year ago. It's likely to become more expensive in the future. Fortunately,
Congress has not hemmed EPA in with fixed coefficients in FIFRA, such as was
the case under the Air Act, where you had to have 90 percent reductions according
to the law, regardless of cost.
I will now discuss the various components of a socioeconomic analysis
in general terms as we presently envision conducting such an analysis. At the
present time, we have not conducted one. We have not made plans to study
any specific pesticide as an alternative along the lines of the framework being
discussed today. And maybe we will not need to conduct one under the Alterna-
tive Chemicals Program.
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Throughout my discussion, please keep in mind that we are thinking in
terms of a time horizon for a socioeconomlc analysis of approximately 5 years
corresponding to the time period for which your registration is effective under
FIFRA before it would need to be renewed. It remains to be seen whether it
will be feasible to thoroughly study a future 5-year period because of limitations
on data and available time to conduct needed analysis on the basis of 5-year
projections.
The first step of a socioeconomic analysis is a review of the production
and distribution system for the pesticide, its registered uses, associated patterns
of use throughout the country, and data on application methods and rates. The
next step is to project use of the pesticide crop by crop for other use over the
time period covered by the study, based on demand and supply conditions. This
evaluation will take into account cost effectiveness of the pesticide in competition
with the problem pesticide and the size of the market for use of the pesticide.
On the supply side, attention will have to be paid to technical and economic feasibility
of producing and distributing the pesticide in needed quantities.
In short, can industry deliver the product and will the farmer buy it? The
projections of use during the period covered by the analysis are critical, because
without them it is impossible to make realistic assessments of the nature and
magnitude of economic and social benefits. Such projections of use are also
necessary for projecting populations at risk and making estimates of total
effects of health and environmental impact, as has been discussed under the
biospheric review.
This section on levels of use would be done jointly by the economists
and the scientists involved in the biosphere review. The evaluation of economic
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benefits is divided somewhat arbitrarily between primary benefits — that is,
those for which the pesticide was purchased by the user — and those which are
secondary or of a by-product nature.
In the evaluation of benefits, we will be estimating the addition to goods
and/or services attributable to the pesticide over and above that which would
be obtained without the use of any pesticide. We may also compare productivity
of the alternative to the problem chemical.
In this analysis, we are aiming for data which will help the Administrator or
other decision maker to determine whether the alternative is a step in the right
direction and/or, further, whether it generates benefits which justify the risks.
It is possible that an alternative does not generate benefits which justify the
risks even though it is better than the problem chemical. In such a case, we would
need to look further for an alternative.
The evaluation of costs is quite straightforward in the case of primary
costs. However, the secondary cost estimation is much more complex as it
covers the unintended and unavoidable cost to users, other parties, and the
environment based upon the results of the biosphere review. Here we will
evaluate In economic and social terms the positive and negative side effects of the
use of the pesticide. It Is obvious that this will be one of the most difficult areas
of analysis in a socioeconomlc review. This part of the analysis will depend
heavily upon estimating exposure/effect relationships as discussed earlier by
Dr. Dale or as developed In connection with the socioeconomlc review.
The social impact analysis area is just now being charted in our office
in terms of the areas to be focused upon and the types of analysis to be conducted.
At the present time, other agencies are active in the area of integrating social
impact analysis into program criteria and implementation. Our major effort here
will be to determine the importance of the pesticide to identifiable groups,
communities, and institutions and to determine what effects will occur if the
pesticide is vastly expanded in use as an alternative, including demographic
factors.
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The social impact analysis Is likely to be of greater scope in instances in
which the pesticide Is of controlling importance in determining cropping patterns
and geographic location of production, such that its use would prevent major
economic dislocations and attendant social impacts on families and communities.
We are not expecting the socloeconomic review to ultimately reduce
Itself to a naive textbook benefit-cost or benefit-risk ratio, but rather offer
indications of the nature and magnitudes of benefits, risks, and costs upon which
to judge whether a pesticide is economically and environmentally acceptable
as an alternative to a problem pesticide.
DR. AXELROD: I wish we had a few minutes just to sit back and think
of what was said and shown here. And, In a very pragmatic sense, and, hopefully,
a very objective sense, anticipate if these kinds of studies, scientific and socio-
economic, were Instituted years ago, would we come to many of the litigations we
have today? Would we be able to iron out difficulties, some of which Dr. Whlttemore
discussed this morning, but not as witch hunts, but where we could delineate the
problems, bring them to the manufacturers and have them work out the problems
before the babies are thrown out with the bathwater?
I think we should, throughout our discussions, rather than perpetrate
adverse reactions or adversary approaches to these new studies and new looks at
these studies, anticipate what benefits rather than risks at least the industrial
sector would go through if Indeed such data bases were developed. Such analysis
should really develop before Important Agency personnel would sign off on cancella-
tions, suspensions, or other adverse effects In which the adversary approach becomes
the master of the situation rather than the scientific, economic, or social aspects.
QUESTION: I was most Interested In your economic assessment. I
think this is very commendable. I know nothing about economics, so I can
speak with some authority on the subject, and at least ask an intelligent question.
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In your analysis, it looks like to me we're talking about rather an
idealized situation. There are two things that sort of concern me though, and
I wonder how you're going to deal with these. One is the current situation that
we're going through of an energy crisis. This has had some impact on the
production of agricultural chemicals. I get various numbers, but, for example,
one group tells me that they are unable to meet their customer demands for
phenoxyherbicides. They can only meet about 60 percent of these. How would
you deal with these kinds of crises ? Can you handle these in your economic
considerations on a long-term sort of an approach ?
The second question that concerns me, and it really shows my lack
of knowledge about economics other than what I see on NBC news, but there
is this. What you say is true about the farmer not being able to go to the market
and pass off his costs to the consumer. But it appears that the drought is going
to have some effect on crop production. And the numbers stick in my mind
something like the corn yields are down 10 percent and soybean yields are
down 13 percent. And this will probably change by the end of the year.
But one aspect of this was that this will be passed on to the consumer,
in reality, in the higher feed grain costs, in the higher meat prices. How can
you look ahead this far in your proposed cancellation and substitution of new
chemicals to determine how this might affect the American consumer ? And
this could be a very adverse effect.
DR. ARNOLD ASPELIN: Economists have conducted extensive evalua-
tion of the impacts of changes in technology, weather conditions, and other
factors such as you indicated. Economic models and theories and most needed
data are available for such things. The problem is the degree of precision.
It isn't much satisfaction to the policy maker who has to go ahead and
make the decision anyway that there are problems in making estimations of
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such Impacts. So we have to make the best use of the available economic theories
and data In generating Information on what these impacts will be to be taken into
account by policy makers In pesticide matters.
Some of these costs will Initially stay at the farm gate, but eventually
they will shift on to the buyers of intermediate products and the final consumer.
It sometimes takes quite a while for some of these things to work themselves
out through the economic system.
As far as the energy problems are concerned, there are an awful lot
of unknowns In that area, too. As Jeff indicated, we are making intense efforts
to assess the market conditions in the pesticide chemical supply industries,
as well as in the demand area, to determine how critical shortages might be,
impacting on 1 year down the road and even looking farther on.
MR. JEFF CONOPASK: I'd like to address the second Question. That
is a very difficult problem and It gets basically to the problem economists have
with some of the sophisticated models that they do develop. We can only answer
certain questions. We hold many things constant In an attempt at answering certain
questions. We can't anticipate everything.
I might take an example from a Corps of Engineers study that was done
a few years ago for a dam in Pennsylvania. The Corps, innovative as It might
be in some of its long-term projections, assessed the possibility of a large
flood in this particular valley. They had what Is known as a once in a 100-year
lifetime flood. And they gave some probability and they used a very, very
sophisticated systems analysis to assess this. Well, it so happened that in
the second year of this project, that 100-year flood hit. So, how can you predict
this ? I'm just, you know, perhaps second guessing ourselves here. But we
just don't know some of these things. And It's very, very hard to predict 5 years
into the future, let alone, 10 or 15.
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DR. AXELROD: Fundamentally, some very shocking decisions may
have to be made on a temporal basis. Ones that no sector sitting here would
immediately accept. Nevertheless, decisions will have to be made on the basis
of impact on this country, to wit, the recent energy crises. Suddenly, a
reassessment of priorities occurred to extents that we didn't think possible. Never-
theless, these modifications of our lifestyle or perhaps our feeding habits will occur.
It depends on the severity and the longevity of these adverse effects and Impacts on
our society.
QUESTION: Would you anticipate that research would begin along use
lines? That is, looking at equivalent substitutes for a given use or throughout
general substitutes. In other words, replacing DDT, replacing deildrin, replacing
1080 with the top substitutes for each of these chemicals or looking at the five
substitutes for DDT or five substitutes for deildrin or five substitutes for 1080 ?
DR. ASPELIN: Focusing research on uses makes sense from the
economist's point of view because that's where the benefits lie. And this would
be helpful, but we don't want to completely focus on uses. I think it would be
helpful to, on a priority basis, allocate research on the basis of uses.
Priority should be given to uses with the most hazardous pesticides, the most
intensive pesticide use levels, and those with the fewest or most limited alter-
natives to problem pesticides.
MR. CONOPASK: One thing to add to that, again our resource problems —
it may be difficult to uncover critical minor uses and I don't have an answer to
that question. There may be some uses that are very small in the agricultural
sector, let's say, which are critical, and yet don't have adequate substitutes.
Hopefully, we can locate these with our resource funding level at the present
time.
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QUESTION: As I understand It, the biosphere review and the socio-
economic review won't be conducted unless a problem shows up in the initial
scientific review or the mini-economic review. These initial reviews are going
to be following along the lines of a registration review, using the same criteria?
In other words, if a person has the information package up to date, as if he was
currently registering a product with the initial reviews, does this not go beyond
those requirements?
DR. AXELROD: Certainly, information from the jackets and from the
registration division will be utilized in that initial scientific review with a
prime focus or foci on those mountain tops we discussed. But the initial
scientific review does not relate to an original registration.
It should be stated here that an inordinate number of registered pesticides
obtained their registrations many, many years ago. Those that have registered
in the last few years are quite different contextually in the areas of initial
scientific review data bases from those that were registered 25 years ago,
which constitutes some of our major DDT substitutes at this time, just to take
an example.
So contextually it will include all the data bases that we have, particularly
those in the registration division. But as Dr. Burkhalter pointed out, there
is an overview review containing all those points that he discussed in his brief
outline of the initial scientific review. It's to bring up any major point of
contention that may find Its way into an in-depth review in the biosphere.
Now we have reviewed a few compounds thus far. It should be stated
that this entire program was only resource committed March 1 of this year.
We couldn't regress into the suspect chemical review. We had to develop a
new thrust of benefit concepts, a broader base than immediately obvious
suspect problems, which is part of the internal review.
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So to answer your question, at least in part, those data bases obtained
from the initial registrations will be utilized. But depending on what data bases
have developed since, they also will be utilized.
QUESTION: Could a good start for a data base be the requirements for
registration as being proposed under the guidelines ?
DR. AXELROD: Absolutely. Particularly under the present guidelines,
which should come out In November '74.
DR. DEAN KATSAROS: I'd like to know how much thought you've given
to how you're going to arrive at this cost figure. In each instance that you will
be considering, you'll be talking about an increase in production over what's
currently being used, because you're going to replace another material. And
you'll be asking questions that even many of the chemical manufacturers don't
know the answers to. If you're going to replace a major pesticide use, you may be
talking about a very substantial increase in volume.
DR. ASPELIN: To pick an example, we might find that a pesticide that
accounts for 90 percent of a use all of a sudden comes into question for cancellation.
Further, let us assume that the remainder of the use is covered by a pesticide
which is being considered as an alternative to that canceled pesticide. The
immediate question is "How much of the void created by a cancellation could
be picked up on an economically and environmentally acceptable basis ?"
think the government and industry and academia have a joint responsibility in
looking at such Issues.
I think as a normal course of business, a firm will be looking to expand
the market for its various products. This represents not business as usual, but
an opportunity to the industry to expand the use.
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And, further, let me say that a pesticide which is economically and
environmentally more acceptable than another one should command a premium
in the market. I really think there's an opportunity for industry and government
to join hands here and make it go.
DR. AXELROD: Someone once taught me way, way back In an introductory
course on economics that there is a supply-demand concept, and that if one can
expand the supply to the demand, prices usually go down. This may have nothing
to do with our present economic situation, but I think that that is one of the supply-
demand rules that they teach you in Economics I. I don't know if it's real.
QUESTION: Along this very same line, let's assume we're under a very
extreme situation where you have a compound that's on the market today that costs
the grower 50£ an acre to use and that is canceled out, and the only alternative
product that is available for that costs the grower $10 an acre to use. But
because of your survey, you just wouldn't be able to make that recommendation.
You just couldn't justify accepting that kind of a spread in economics.
On the other hand, if I had your endorsement of my product, which
costs $10 a pound to put on, I could then expand my production and put it out
for $5 a pound. This might be within the realm of acceptability. What do you
plan to do ? What is your program in regard to working with products that
are in small production or new production for which the price is at what we
might call a development price, as opposed to a product that has reached
maturity and is at a much lower price ? Are you going to throw it out because
of that? Or have you even thought about it?
DR. ASPELIN: Well, as I Indicated, there would need to be an analysis
of the potential for increasing the supply of the product. And this is going to
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involve looking at the impacts on cost as you increase the quantity. It may well
drop from 10 to 5 to 4 to 3 to 2 to 1. It may, as you increase quantity, also
drop the second year after you go into production. Or maybe the best available
control is considerably much more expensive, and if there simply are no alter-
natives and the market will not stand for the use of the $10 compound, you're
going to have to result in no use and the price could conceivably have to go up
to the consumer.
If there's no way that the farmer can afford to pay the $10, the product
is obviously going to be produced without it. Now, hopefully, this will never
be the case. The impact on the consumer will depend on how important that
$10 is. If the $10 per acre compares with the total production cost of $200
an acre for the product, there would be a fairly nominal increase in the cost
on the market of the delivery product.
On the other hand, if the $10 is half of the cost or something of that sort
like it might be on wheat, it would be very substantive. But hopefully there will
be economic alternatives within a near range in cost to the one in question.
QUESTION: Would you anticipate that a substitute chemical might be
completely acceptable from all standpoints except economics and would be thrown
out on the basis of economics ?
DR. ASPELIN: We would not throw it out on the basis of economics. The
realities of the market in which it's used will make the decision. If the best the
industry can do is $10 on the cost of the pesticide, the market is going to have to
determine whether it can justify its use. In other words, can the input market that
the farmer is in justify using it? If it doesn't return $10 plus something else, he
simply won't use it and you'll produce the commodity without it.
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DR. MORRIS CRANMER: If we could get away from perhaps the produc-
tion costs in this economic equation for a minute and think about the health effects
or just the effects costs of providing equivalent data bases for making some of our
decisions. I believe Dr. Axelrod directly referred to the fact that different types
of data bases are available for different compounds which have been used.
As a generalization, compounds In heavy use and In long use have a larger
amount of effects data accumulated on them. I would think that we would, in making
this type of decision, want an equivalence of comparisons, and Is It Included In the
analysis and economic determinations of how much it would cost to go through these
machinations with various other compounds ?
In other words, L. your cost assessment analysis, do you determine how
much it would cost to generate equivalent health and effects information on the
several candidate compounds that might be considered as replacements ?
DR. ASPELIN: As I indicated, the socioeconomic review would attempt
to evaluate the costs of avoiding health effects, the cost of treating health effects,
and this would be at the levels of use of the pesticide that would occur as a substi-
tute for a canceled compound.
We would be doing these comparisons with the pesticide that's being can-
celed more or less on a one to one basis to see whether we're going in the right
direction. But you can't limit your concerns to one particular area. It may well be
that it will be very expensive to develop the necessary data, to evaluate the signi-
ficance of health effects In economic and social terms. But It's going to have to be
done, and it would be done in such a way that you would know whether you're making
a step in the right direction as you go to the other compound.
DR. CRANMER: It occurred to me, perhaps not being as familiar with the
subject as you, that in order to make your long-term assessment of health effects,
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effects on the human population, one would have to have equivalent data bases to
make that projection from. And, since biological Information — for instance, the
toxlcologlcal Information data bases — will be dissimilar for the various compounds,
in order to make an equivalent projection, you would need to at least adjust these
data bases.
And this might be sort of an early process, I would think in my own mind,
prior to the time of getting into some probability assumption of costs of future health
effects of a compound that we have insufficient Information on.
DR. AXELROD: I don't quite follow part of your discussion, Morris. If
you have a pesticide which is useful on 10 acres, are you proposing that we obtain
equivalent human health effects on that as we would commit resources for something
which Is used on 100 million rcres?
DR. CRANMER: No, not at all. That's one of the easy parts of the equa-
tion. Let's say that you have approximately equal projected usage rates In usage areas,
but you have a dissimilar toxicologlcal information base from which to make your
projection.
DR. AXELROD: This is going to be presented by Dr. Buckley tomorrow,
because he sets Into place the data base retrieval possibilities for human health
effects, as well as other ecological ones. And he will have to assess the priorities
of which goes first for the resources committed In retrieving such data bases so
that Dr. Aspelln can make the right economic assessment.
DR. R. E. HANSON: One could ask: When you get this data base, $5 million
looks like a very minimum amount of money, yet when I hear the programs, that is
exactly what you're talking about — if you had $5 million and you get another $5 mil-
lion for '75, that is If you're lucky. Or Is that already committed for 2 years?
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I mean, addressing the question that was just asked about bringing things
up to data bases, I mean, two toxicology trials, for instance, if that's one of the
data bases you're looking at. I don't know— $65 to $100,000 per chronic trial. Five
million doll ars goes pretty fast.
DR. AXELROD: The equation, of course, relates to not overstepping what
resource commitments you need for the number and type of substitute chemicals
you study. I mean, to take it out of perspective Is an exaggerated situation. You
wouldn't take one chemical compound and commit the $5 million in research for that
compound. You would have to assess on a variety of levels the proportionality of
commitment.
Now, I don't know particularly what your thrust Is or what your answer is
to what you're asking, because you ask your question with an answer behind it, and
the answer is in your mind. But in government you kind of live day to day. And you
sometimes reassess your priorities every hour. And all you can do is try to rise
to the occasion and to assess the needs of the moment and address them. And then,
what happens tomorrow, little things like vetoes on appropriations bills, you deal with
as it comes along. It's good in two directions. First, because It gives you flexibility.
Second, if you don't act that way you get nothing done.
And the real name of the game is to get something done and get it done in
as good and as contributory a fashion as possible — scientifically, economically,
what have you. I think it was very Important that It was brought up that whatever
decision Is made, whatever policy Is formed, that was today. Five years from
now, it may be completely different, or 5 months from now it might be different.
Decisions were made a few years ago that we're still living with, still
trying to understand. So, the name of the game in government is rise to that occa-
sion and keep plugging.
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But I feel that we have a 2-year commitment to a program. We've assessed
what portions should be studied, where the money would go best. We get the best
data retrieval to serve not only government, but the industrial sector, so that they
can have a better appreciation of where problems may be found if resolved by their
efforts in research and development on a much broader base than perhaps they can
look at themselves.
QUESTION: Manufacturer of compound B takes 2, perhaps 3, years before
he expands capacity to be able to take over 100 percent of the market. What do you
do on compound A during that 2- to 3-year period? Do you give a temporary exten-
sion of its registration for 2 or 3 years until the other one comes in, or do you
cancel it now and leave the farmer without pest control for that 2 to 3 years ?
DR. ASPELIN: Obviously, this type of a trade-off in terms of time needs
to be considered probably a lot more than it has been in the past. There are some
options for the timing on these things. The all or none and right now type of deci-
sions are very expensive.
And, as we all know, markets take time to receive signals and to do things
to make adjustments. Instant changes, instant cleaning up of the environment, is
very expensive. For some of these decisions, the sooner the better, obviously.
But maybe the cost isn't worth it that quickly. So there are trade-offs through
time that should receive intensive policy type analysis.
QUESTION: Is there coordination between this program and the other
divisions so that cancellation occurs at the right time ?
DR. ASPELIN: You're getting over into the policy area, which is beyond
the economics, but there does need to be this type of policy analysis at the end of
the kinds of comprehensive analyses in the various areas that we talked about today.
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DR. AXELROD: One of the major thrusts, though, of the Office of Pesti-
cide Programs is to synchronize the efforts of the Registration Division, Criteria
and Evaluation Division, and Technical Services and Operations Divisions. And it's a
new office. The divisions are new. This Is not begging the question, but it means
that there are many roads ahead of us in which requirements for genuine synchroni-
zation of efforts and decisions at other levels will have to be done.
DR. JERRY SMITH: In the economic equation, are you considering only
domestic economics, or are you considering International economics as well and
the effect of changing any cost to the farmer in his ability to compete Internationally ?
DR. ASPELIN: I think Mr. Conopask alluded to the fact that we Indeed must
consider the impacts and the realities on an international basis, but we start out
working at the middle of th°< problem, which usually is pretty close to the farm gate.
And we work out from there. But we do have to recognize the international Impli-
cations of what we do, and the implications of things that are happening elsewhere
in the world. But we're not on an Island, economically or any other way. And this
is an Important area of Inquiry and we will not forget It.
DR. AXELROD: I think It's Important to state that you all have many ques-
tions and, believe It or not, we don't have all the answers. The stimulus you give
us in these areas of questions will be addressed. They are not a matter of verbal
pitter-patter. They are a matter of deep concern to us and to the Agency. These
questions stimulate many Issue papers which will be developed In the Office of
Pesticide Programs.
It is the beginning of a program in a positive sense to help. These ques-
tions, and, hopefully, some forms of answers that we can derive over the next few
years will help in that decision-making and in the policy-making of the agency.
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MR. ALFRED MITLEHNER: In line with what you just said, I won't ask a
question, but I'd like to express two points of concern. One is, from the point of view
of the socioeconomic review that's going to look 5 years ahead, I find it hard to under-
stand how such a review could be meaningful if this does not include the introduction
of new compounds, particularly those compounds very near registration. It seems to
me that it is these compounds or potential products that will have the greatest effect
upon what happens in the marketplace.
Secondly, a very mechanical problem. I am very concerned that file jackets
do not find their way into this initial review process and are excluded or lost from an
ongoing review of a current registration request.
DR. ASPELIN: Let me respond to the first question. We will not ignore
any significant factor affecting the demand or the supply for a substitute pesticide
in the course of the evaluation of its potential. And if there are alternatives that
currently are not registered, but are likely to be registerable down the pike, this
is not the focus of the program but we will not ignore these things if we can develop
scientifically valid data as a basis for taking them into account.
DR. AXELROD: We've gone through this exercise of making sure that those
jackets are never taken out. That's the beauty of the Xerox machine and the beauty
of Dr. Rogoffs capacity to overview the situation and very careful attention to trade
secrets, to confidentiality of data, and so forth.
DR. G. W. PROBST: We've heard much about mini-reviews, mini-economic
reviews in a system of phase one and phase two for evaluating pesticides, which, to
me, Is a model of thinking and planning rather than a reality situation. I would like
to address one question. We are attempting to establish criteria for substitutes or
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alternatives to the so-called suspect chemicals. Don't you think it might be wise
to select one of the suspect chemicals and check it through the proposed model
and determine how a suspect chemical will fare ? It might fare pretty well —
including in a socloeconomic situation.
DR. ASPELIN: You're saying take one of the suspects we have and . . .
DR. PROBST: Test the model.
DR. ASPELIN: And test it in this type of socioeconomic study model.
DR. PROBST: As I understand, this has never been done. Is that correct,
Dr. Aspelln?
DR. ASPELIN: We have not conducted the comprehensive review of the
sort talked about in a review mode. Obviously, considerable amount of data have
been generated.
DR. AXELROD: As a matter of fact, even in the Internal reviews, until
very shortly, to just a year ago, the requirement for socioeconomic studies was not
part of the review process. It has been locked in by law, and the development of Dr.
Aspelin's branch has been a very recent evolvement in OPP. Without asking for extra
money, we're going to do that. Not going to talk about it much, but we're going to do
that and see how it looks — might/be very interesting.
i
QUESTION: I certainly .wouldn't be one to be defending or saying anything
about DDT, but that might be an/Interesting one to send through the economic review,
particularly with the disagreement between the hearing officer and the past Adminis-
trator of EPA it might have anjinteresting result. Aren't you reviewing that anyway?
DR. AXELROD: As t>\ matter of fact, the legislators have asked that the
Agency review the scientific t
account the social and econorr
/
isls for the Administrator's decision, taking Into
c consequences of the decision. And I think that gives
you an answer.
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DR. EDGAR TURTLE: I don't think it's specifically a question I wanted
to ask, rather more in the form of an observation. I heard one of the reviewers,
when talking about possible cancellation of registration, looking at the position of
the manufacturers with their supplies and calling into his calculations the fact they
might be able to sell their materials abroad.
I might say I, in my present seat, am looking at this discussion from
abroad, namely, the repercussions abroad on the actions taken in this country.
And I think perhaps DDT is one example there. There tends to be an assumption
here. The statement "Well, manufacturers might not be so badly off, because they
can sell this stuff abroad" was the sort of answer which was given to our manu-
facturing question.
Now, it seems to me the same thing works the other way around. That was
just to meet the first year or so because the manufacturer has got some material
on hand and he wants to get rid of it. There has been a cancellation of registration.
He can sell It abroad and these people overseas, therefore, benefit from It.
But 3 or 4 years later, because of this cancellation of registration, the
cost of this material to any purchaser depends upon the amount which is manu-
factured. Therefore, the person abroad, who now wants to get it, because your
decisions don't directly affect him has to pay a lot more.
Now this may be a pesticide which Is used, for example, In vector control,
which now is going to cost a lot more. The only point I'm making Is that In your
socioeconomic assessments, could I make a plea that you at least cock an eye on
the effects overseas, on these facts perhaps from a humanitarian point of view, not
only from the point of view of how much more profit the American farmers will make
or the American manufacturers will make? What are the effects on overseas in a
socioeconomic sense?
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DR. AXELROD: It's well put, Dr. Turtle. I think that Jeff Conopask and
Arnold Aspelln both more than alluded to the fact that when people are making deci-
sions based on socloeconomic studies, a good portion of them will address the
international question.
I also think, personally, that in the light of humanitarian work, if we were
to take a recent past example of DDT, I don't know that the use of DDT for human
health, which still is on the books in the United States and in the world, if the cost of
that should be borne by society, by international organizations with stipend or sup-
plementation. There are very many questions that your question brought up as to
how to handle, on an International basis, compounds which in an affluent American
society, the United States, has seen fit to dereglster or cancel, that the require-
ments for the American scene may be different from the requirements on the inter-
national scene in emerging countries, where they are more worried about tomorrow's
breakfast and if there's going to be one, than whether they are going to suffer dire
consequences when they're old. I think this is part of a very basic question as to the
position the American EPA has on the international scene, both from its Impact on
decisions that are made at EPA, and also on the conscience of international organiza-
tions as to how they handle these things where there is a question of humanity.
MR. CHARLES KRISTER: I was hoping that the two gentlemen from the
International agencies (WHO and FAO) would also make the same sort of plea to
some of our European counterparts when they take their actions. There's been a
tendency on the part of some of the countries to take very precipitous action In
connection with certain suspensions or cancellations. Perhaps they too are
setting a pVttern which Is undesirable.
I'd like to ask another question, perhaps of you or Dr. Korp, and put It in a
little different light than Mr. Mltlehner did. With all this planning going on — mini-
reviews, Internal reviews, substitute chemical reviews, etc. in the Agency, what
impact do you expect this kind of activity to have on registrations and In your toler-
ance clearances for new products or for additional new uses for existing products ?
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DR. KORP: Well, first, I don't think that they're unrelated, but I don't
think that it's going to negatively Influence the registration process. In other words,
our procedures there will be to accelerate the process to do the very best we can
to get answers back promptly and quickly, using these guidelines that Len now has
promised for November, and, as I say, so the inputs will go back and forth, there's
communications. But I don't think that you're going to have this program influence
the registration program.
DR. AXELROD: In a positive sense, the good that can come from it is that
we can have a much sharper, realistic approach to criteria for registration,
criteria for the positive side of looking at registration.
QUESTION: I'd like Dr. Dale to expand on his comments that there's some
sort of a tissue review. Whai, are your guides ? Would you explain to me about that ?
DR. DALE: I didn't say specifically there would be a tissue review, but, for
example, if the question of safety hinged upon a study which was based on a histolo-
glcal examination of a slide, say, hepatoma, we would rerevlew these slides and
determine If, Indeed, by using experts in the field of pathology, this is really a
hepatic carcinoma or not, if the slides are still available.
In other words, going back Into the original study In greater detail than
merely reading of It In the Initial scientific review and reviewing what has been
written about It, going back and looking at the raw data in depth.
QUESTION: I am currently aware that manufacturers are not required and
have not the volume of tissues or slides for a review by EPA.
DR. DALE: They have, In some cases, provided slides when there was a
request. Not routinely, no.
QUESTION: Could I ask whether or not they anticipate that this would become
more of a formality In the future, particularly with regard to registration of new
products that they indeed would be looking at tissues and the slides?
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DR. DALE: I think In regard to certain types of pathology, simply better
record-keeping.
DR. AXELROD: I think it's a matter of intensity of need. In the usual regis-
tration process, data is brought forth. On the basis of that data, decisions are
made at the registration level. Later on, perhaps, in a case of suspect chemicals
internal review, you have to take a much greater in-depth look. Either you expe-
dite new studies to assess lesion, or, as Dr. Dale puts it, the privilege of a number
of experts looking at the original slides for diagnosis.
And this Is a very real possibility. I think that we have had excellent coopera-
tion from some industrial sources who saw fit to have confidence In their own exper-
tise, who made decisions concerning lesions of various sorts. And this visibility Is
one which Is not only justified, but Is heartily acceptable to those who are trying to
assess In a scientific fashion the credibility of a former decision.
We all know that particularly in pathology it's very hard to get two patholo-
glsts to agree. The best you can do Is get a concensus of opinion, and that some-
times looks like that animal that's put together by a committee. That's what we're
trying to stay away from.
I think I'm right by saying the way those slides were given Is, you know,
people get into an adversary hearing and then slides come out of the bags. And
a lot of time, a lot of money, and a lot of manpower is wasted. Those slides could
have gone into the hands of scientists to begin with, and, hopefully, a decision
could be made that you wouldn't need an adversary hearing to determine in an
adversary way whether that science is right or wrong.
QUESTION: Two questions: One, has the proposed program as outlined
here been reviewed by the Office of General Counsel in EPA particularly to evaluate
It In terms of the liability of the participants In case of recommendations that came
out of the program that later were shown to be obviously wrong?
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And the second question: There have been a number of references made with
respect to safe, safer, during the discussions. How do you square these with the
prohibition in the statute and in the legislative history, with respect to essentiality?
DR. AXELROD: What you're saying in the first question is "Is every deci-
sion made in the Registration Division, based on data forwarded by registrants,
reviewed by the Office of General Counsel to determine whether that reviewer is
liable for his decision?" Practically the same parallel exists when scientists are
asked to make decisions on the basis of the best expertise knowledge and consulta-
tion with others in the field if they make a decision which later on proves wrong,
whether one goes back and decides on double indemnity or liability of his decision-
making process.
I presume that none of us here in this room have been without error in their
lifetime, and I think your question is peculiarly biased as to this program, because
scientific decisions are made every day in various aspects, and they're not unique
to EPA or unique to the field of agricultural chemicals. There will be errors made.
But the best defense you have against error is careful, scientific, expertise deci-
sion, not an adversary approach.
QUESTION: The reason for the question is that this is a new program within
the Agency, as I understand it. It's a new approach. And other decisions within the
Agency are certainly subject to different types of legal appeal, all of which are set
forth In the statute.
My question Is not with respect to an individual decision of this particular pro-
gram, but whether or not the Office of General Counsel has looked at the program as
a whole to evaluate it from a legal standpoint.
DR. KORP: The program was put together by OR&D and OPP. It was
reviewed very thoroughly by OPM, which is a planning and management group, and
I'm sure they have a General Counsel view. I think they're thoroughly aware of the
program.
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DR. AXELROD: It has also passed what Is called the tenth floor. That Is
the OWHM which Is loaded with lawyers who have made many comments on the basis
of some of the things you're discussing. And long before you saw it, those things
were either enlarged upon or removed. There are four lawyers up there who went
over this program before It was sent to you or anyone else.
I don't know if that's sufficient unto itself, but it comes under purview of the
same type of thing as the internal review or the registration review. It's a new
slant. Hopefully not as an adversary approach, but as a constructive one. Never-
theless, it's a new program.
DR. AXELROD: In answer to the second question, I think earlier in our
discussions I brought up the fact that words like adverse, unreasonable, and safe,
are subject to all the subjective enunciations of biases of people. And we're all
people, scientists or otherwise. And we do have one very important thrust con-
tractually to delineate definitions, definitions of various words thrust upon us by
the new FIFRA, such as unreasonable adverse effects, hazard, imminent hazard,
'i
risk, benefit, made by good legislators but perhaps without the need to delineate i.
-•*1*^
meaning to these words, leaving It to us. We are in the process of getting the legal,
medical, social, economic, and other definitions of these words, hopefully, to more
objectively utilize these words and their meanings In constructive decision-making.
We all recognize how faulty a word "safe" can be.
Now, at the extremes of any equation or curve, It's simple. 10,000 people
die of something, It's not safe. The question of whether six people dying out of so
many is safe or not, that's a matter of risk and benefit analysis that really reverts
back to enunciation of safety or not. We are very much cognizant of the risk one
takes hi enunciation of what safety or hazard or unreasonable or just adverse effects
means, and we're studying that problem.
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QUESTION: I'd like to refer back to a comment you made this morning,
and maybe it's also related to what you were just saying, but you indicated this
morning that the internal review process on a material begins at such time as
there are concerns raised that you begin to study the problem, which may also then
get us into the alternate chemicals review.
My question is, specifically: When does the noise level become high enough
so that you begin and what are these various types of criteria? The accidental
spill yesterday in Yuma — is this a type of thing that is a factor ?
DR. AXELROD: That question, I think, is somewhat out of sequence. We
will discuss what initiates the Internal suspect chemical review, but the part that
you said leads to substitutes, that doesn't lead to substitute chemicals reviews.
Very pragmatic aspects lead to my being impacted upon for an Internal review.
For example, Dr. Korp says, "You will review this. " Now, you may not think
that's a good answer, but I consider it an excellent one. Or Mr. Agee says, "Dr.
Korp, you will have Dr. Axelrod review this." It's a very good answer. And that's
serious, because it Isn't a matter of that good saying about "Ours is not to reason
why," but, nevertheless, these people are impacted upon by various situations, some
of which are just, frankly, political.
A couple of senators say, "You better make a review. We think this is a
terrible compound." It becomes impacted upon the various levels above me, and
somehow It filters very decisively into my division and we're making a review.
So, there're various reasons, various accusations made, various questions
asked by many sectors — political, Congressional, environmental groups, etc.,
which come down In the form of "Lenny, you will review this compund now. " And
I really can't give you a better answer, because that's it.
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QUESTION: I Just want to make a comment, rather than pose a question.
It seems to me that In this whole review process, science will best be served if
we can keep this on a scientific dialogue through much of this review process.
When it becomes legal, things get tough. You know what I'm talking about — recent
situations that we've had that when the legal arm moves in, dialogue dies. And I'm
sure that you're going to think about this in your overall matrix system, but the
protagonist and the antagonist can speak freely and argue scientifically and trade
data and call each other on the telephone, and send papers within the constraints
of the Agency. But I'm also aware of some experiences we've had that when the
legal arm moves In, this sort of dialogue dies. And I would hope, speaking as a
scientist, we could keep our channels of communication as open as possible.
DR. AXELKOD: I should think It would be perfectly obvious to everyone In
this room that the thrust of this program is scientific, that It Is Aristotelian logic
and not Platonic. That Is, we are certainly not going to accept the adversary approach
in this review concept. Some of my best friends are lawyers, but this is not their
place.
Hopefully, by astute scientific decision-making, we can keep it from the need
for legal entrance into the situation. And I do agree with you that in many instances,
with everyone being as honest as they can possibly muster, once science enters into
the Platonic dialogue, a very fundamental basis disappears. And It's not this Agency
It's anyplace, because the Platonic logic Is one of adversary approach and winning
the argument. Scientists love to win arguments, but It's not the thrust of science.
It's examination and prediction on the basis of something. I agree with you.
MR. TOM BLUE: As an extension of an earlier question about criteria for
placement on an internal review list, you were mentioning that most of these criteria
are essentially external from the Agency. However, can you explain if and how in
the mini-economic review or soclpeconomlc review system where you may decide
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a product is not a suitable substitute, the criteria in the review process may make
a product jump from one list to another?
DR. AXELROD: I would hesitate, as Director of the Criterion and Evalua-
tion Division, to visualize that what impacts on us to make a review are "criteria."
The things we just bantered back and forth concerning what leads to an internal
review, I wouldn't consider criteria. They are needs, they are pressures, but
they are not "criteria."
On the second question, or second part of the first question, Dr. Dale pre-
sented one, a very pragmatic and second, a more hypothetical approach to scientific
reviews for these alternative chemicals. Contexturally, in those slides were the
very basis whereby the proposed hazard for the compound will enunciate a further
review. The initial scientific review, the Initial mini-review, does not enunciate
any proceeding except to go on to in-depth studies.
QUESTION: Let's say you have a hypothetical case, and when the initial
scientific review is conducted, you find that you're deficient in data. But the pro-
duct is not proprietary and it's manufactured by a number of people. With the new
section of the law on compensation for data, how will it be handled whereby several
manufacturers are going to be involved in this and there's going to be data needed
to be generated? Has some thought been given to this?
DR. AXELROD: Yes. That's the basis of a large portion of Dr. Buckley's
thrust In the Office of Research and Development. And no more can you get blood
out of a stone than Information from people who are not making profit. So the need
to fill data gaps in a non-proprietary compound would hardly be filled by the indus-
trial sector. And we would turn to either ongoing programs and acade'mla, or Inter-
nally to either other government agencies which have similar projects on stream or
to Dr. Buckley's group in the Office of Research and Development for that type of
data development and retrieval.
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We want to thank you here at the podium for your indulgence in listening
to these review concepts this afternoon, and for, hopefully, digesting them, and
for the questions that you've asked. It has given us more food for thought for the
development of the program and for other interesting ideas for the future.
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PROGRESS IN EPA RESEARCH: NEW DIRECTIONS AND OVERVIEW
John L. Buckley, Ph. D. *
I'd start out by saying that it's nice to be here. I listened all day, and I
had the distinct impression that every time a particularly tough problem began
to loom, Leonard said something about, "And, you can ask Dr. Buckley tomorrow. "
What I did want to speak briefly on is who I am. I don't mean as an
individual, but with a title like "Acting Deputy Assistant Administrator for Pro-
gram Integration," what image does that evoke? It doesn't tell me anything.
Therefore, I decided it would be useful to spend a very few minutes speaking on
the organization of the Environmental Protection Agency in relation to research,
knowing that for many of you here, this is old stuff, but knowing also for some of
you, that it's not. So, forgive me, those of you who are eminently knowledgeable
about this.
The organization is headed by an Administrator with a Deputy, and there
are five Assistant Administrators. One of these five Assistant Administrators
is an Assistant Administrator for Research and Development. Under him there
are a series of Deputy Assistant Administrators, and I'm acting as one of those.
Incidentally, the Assistant Administrator for Research and Development is also
acting, since the last one resigned on May 24, 1974.
The other Assistant Administrator of particular Interest to us here Is
the Assistant Administrator for Water and Hazardous Materials, Mr. James
Agee. It is in this group that Dr. Korp and my colleagues in the Office of Pesti-
cide Programs work. So, a point to be made, in a sense, Is that we work in two
different parts of the organization. We both deal with pesticides. But, at the
*Acting Deputy Assistant Administrator for Program Integration, U.S. Environ-
mental Protection Agency
~ 99
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time that the Environmental Protection Agency was created, there were bits
and pieces that came from quite a number of places.
There were research groups that dealt with pesticides and effects on
humans. There was a large program in relation to water pollution. Many of
these research groups had similar functions. For example, many of them had
health effects research, research on the effects or the fate of substances in the
environment, research on analytical methodologies for various compounds and
various substrates.
In trying to rationalize the organization in terms of getting the most done
for a given number of dollars (which over the period of years, has diminished
rather than increased), it seemed to us most useful to organize in terms of
health effects, ecological processes, fate and effects, analytical measurement
methods, monitoring, and control technology.
We now have in the Office of Research and Development, a Deputy Assistant
Administrator for Environmental Sciences, which includes health and that sort
of thing; one tor Environmental Engineering; one for Monitoring Systems; and
this other one for Program Integration.
After a couple of years, we in Research and Development thought that we
knew what we were doing and that what we were doing was pretty good and respon-
sive to the Agency needs. But it turned out that the rest of the Agency neither
knew what we were doing, nor felt they had any Influence on what it was that we
should do. Then the Office of Program Integration was Invented to try and serve
as a communication link between the rest of the Environmental Protection Agency
and the Research and Development group in order that research in this regulatory
agency could respond to the real questions and the real problems In the most
efficient way — so that we weren't, in the view of the rest of the Agency, "doing
our own thing."
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We're organized In a headquarters staff relatively small, though often
considered excessive. The main function in headquarters is in planning, alloca-
tion of resources, and staff support functions.
Our operational research program is carried out through the National
Environmental Research Centers (NERC's) and an additional center called the
Washington Environmental Research Center. The Washington Environmental
Research Center is concerned with socioeconomic research. The other four
NERC's are in Corvallis, Oregon, in North Carolina at Research Triangle Park,
in Las Vegas, Nevada, and in Cincinnati, Ohio. Each deals with different sets
of problems, though these are not exclusively their provinces.
That's probably more than enough, except that I want to emphasize the
point that the operational conduct of the research program, once planned and
agreed to, is the responsibility of the National Environmental Research Centers,
and not of the Headquarters Staff. This is true not only in the intramural work
they do in their own laboratories, but also in the expenditure of funds in extra-
mural activities, in both grants and contracts. It's somewhat fuzzy in terms of
interagency agreements. Some of these are done from headquarters; others are
done in the field.
From the headquarters we do transfer some money, on the order of $4
million a year for the last several years, to the National Center for Toxicological
Research, NCTR, in Jefferson, Arkansas. Dr. Cranmer, who will be heading a
session tomorrow is the Director of NCTR.
The reason for this particular operation is that long-term, low-dose effects
seem to us an Important part of our program. How one evaluates these, how one
can extrapolate from animal data to man — this whole set of problems dealing with
human effects that are less than obvious is the major responsibility of NCTR, and
we actively support this in a financial way.
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Dr. Cranmer can tell you, if he chooses, the managerial arrangements.
Suffice it to say that the Food and Drug Administration is the other contributor,
larger in scale than EPA, and they are the managers responsible for the program
there, except that the program is substantially influenced by a policy board made
up of both agencies.
•-- "• As far as how much research we do In terms of dollars, the 1975 antici-
pated budget before the veto that took place a couple of days ago was on the order
of $140 million, plus a somewhat larger amount for energy research. Of that
$140 million health effects has a little over $35 million. Ecological processes
and effects has nearly $40 million. Monitoring systems, which includes analytical
quality control and analytical methods development in all media, has about $20
million. Technology development In air and water and solid wastes has a little
more than $40 million, and the socioeconomic effects research has about $5 million.
Broken out by media and categories, air has about $57 million; water including
water supply, just over $45 million; pesticides including alternative chemicals
nearly $11 million; with radiation, solid waste, noise, and interdisciplinary research
having the balance.
I think that's probably all that I need to say about the mechanics.
I want to come back to the fact that the responsibility of the Office of Research
and Development is clear. It is the provision of data and the scientific Interpretation
of data. It may, at a policy level, also influence decisions in the Agency. That, how-
ever, is a separate function and not to be confused with the other.
According to the program, I am to talk about new thrusts in pesticide research.
In looking back there are many things that we know now that we didn't know a
decade or a decade and a half ago. There are a lot of things that we know now to
look for that we didn't even believe existed then. And there are a lot of these things
that are very comforting to us. It's clear, for example, that things don't accumulate
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indefinitely in anything. If they did, the outcome, of course, would be human
beings made up a pure DDT. There's always some kind of a dynamic balance
even though there are many details about how such a balance is acquired that we
don't know.
But there is a lot about it we do know that we didn't before. What I want
to talk about briefly in what was labeled as "new thrusts" is that I believe that
one of the most important things that the Federal government can do is to parti-
cipate in methods development for assessment of pesticidal and other chemicals.
Assessment in the sense of predictive in relation to safety — how can we predict
better ? How do we predict as rapidly as we can and as reliably ? What happens
to a chemical or what will happen to a chemical in the environment? What kinds
of transformations occur ? How rapidly do they occur ? How can we predict the
events that are likely to take place over a long period of time? Over a short
period of time ?
The question of how you can better make judgments and acquire data that
will be useful, is an important one, and that is a kind of a driving force in many
parts of our program.
It's true in analytical chemistry. It's true in the use of model ecosystems
to evaluate fate of substances. It's true in support of the activity of NCTR, where
again we're interested in predicting at an earlier time rather than waiting a human
lifetime.
This is one of the areas that we feel very strongly about. Probably we will
put more effort into thinking about how you do this with new kinds of pesticide
chemicals, the viruses, bacteria, pheromones, and other things of this sort. It
isn't that these substances are necessarily all that widespread or important yet,
but the fact is that we don't know much about these substances and we're not even
sure yet what the right questions are. Therefore we think new methods in that
area are Important.
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You may note that we're not doing much about it yet, but it seems important
to me to deal with the non-pesticidal ingredients of pesticidal formulations, those
things that all of us in the past have tended to call inert.
We have another program which is called "Alternative Methods of Pest
Control," not to be confused with "Alternative Chemicals." The reason it has
this name instead of integrated pest control or something of the sort is that we
don't want to exclude from it chemical pesticides or other chemicals. We do want
to exclude from it some of the routine usages of existing more or less conventional
chemicals.
Another thing that we1 re trying to deal with is understanding of the relation-
ships between biological events noted at high levels of dosage or exposure in rela-
tion to "real world" levels. How do you utilize information of that sort or how do
you extrapolate it to the levels which are believeable or expectable, even in an
extreme case in the environment. I don't have answers but it's one of the driving
forces of trying to think about problems of this sort in terms of the real world.
Now if you want to know in any detail about what we're doing, I'm not going
to tell you. This room has a fairly large number of people who are recipients or
holders of grants and contracts and who are people from our own laboratories.
I'm not going to try and list them all because if I do, I will surely miss some. I
would encourage you to ask questions of them, particularly in the Friday morning
session. If you have any specific questions before that, deal with people who know
and not with me, as I am now solely an administrator and communication link
between people.
I couldn't overlook the opportunity to make a few gratuitous observations
on the basis of sitting here through the day. It seems to me that many of the kinds
of questions I have heard, and the implications or connotations of them, could be
overcome with an attitude of openess and cooperation. I think I've heard the word
"witch hunt" used here. I think there's a certain element of suspicion and I guess
I think from my point of view that it's probably unwarranted.
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I think that EPA, not only in this program but throughout its other pro-
grams, is bound by its Administrator's desires to act in an open fashion. We
probably are more open than any other agency. We have taken to heart the Free-
dom of Information Act. And I can tell you, on those rare occasions when we
haven't, the courts have made us wish we had. The point I really want to make
is that EPA has behaved and is obligated to behave in an extraordinarily open
fashion in making its decisions.
There is another item I'd like to discuss. We've talked about this Alter-
native Chemicals Program as though it were brand new and in a way it is. On
the other hand the same process has been going on long before there was an
Environmental Protection Agency. The process consists of the evaluation of a
substance and the decision that it will do a certain thing and that the risks asso-
ciated with it are bearable. The ground rules under which the decisions have been
made tend to change with the passage of time, but, nonetheless, the laws have
always dealt with both efficacy and safety, and have required consideration of
both the risks and the benefits.
It seems to me that what has happened is that now we have been told in a
sense by the Congress that we weren't doing as good a job in making these deci-
sions and in weighing the risks and benefits as we ought to have been. We've now
formalized a program and to some extent maybe we've compartmentalized it, and
we're now describing it in much more explicit terms. We hope it will work better.
Nonetheless, it's an extension of a process which has been going on for a very
long time.
I would note that it's not substantially different than any other standard-
setting process that goes on in EPA, in the sense that you go through a scientific
evaluation of what's known and you look at the benefits and the risks, using the
best data available and, on the basis of this, you make a social judgment.
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Now unfortunately we don't have a world largely populated with Solomons,
and from time to time the decisions can certainly be faulted. I think it's impor-
tant to bear in mind that if we make the decisions openly and if we describe with
some precision the basis on which they're made, we can be faulted for not being
Solomons but we won't be faulted for being dishonest or stupid. I think that's what
this whole process is about.
We all know much more than we did before. We know a lot of questions
that are important to ask that we didn't know before. The social climate in which
we all live and the attitudes of people are different from what they were in the past.
Summing up in a way, I would have said that there was no way that anyone could
have predicted some of the events which followed the introduction of DDT. Nobody
knew about bloaccumulation of synthetic chemicals. Nobody knew about some of •
the transformation processes that took place. There were a whole lot of things
we learned, and I would submit that the decisions that were made about DDT in
the early days to permit it and to use it the way it was used, were absolutely
without fault.
I would submit that on the basis of what we know now, one wouldn't have
made those same decisions. In a sense, one DDT was inevitable. A second one,
in the same sense, is probably inexcusable. We know more. Our understandings
are greater. Our sense of values has changed. What's important is that we use
the insights that we have and that we draw together the knowledge that we have.
Moreover, we've tended to talk today as though these decisions come out
as yes or no decisions, and I suppose finally in a way they do. But never are they
really simple yes or no decisions. It's always kind of a muddy shade of gray that
you deal with and the man who makes the final decision must select some point
at which he makes the decision.
There is also the question of available data. I can't think of a single deci-
sion that I know of being made in which all the information one would like to have
is available. Yet for an assortment of reasons it's necessary to make decisions.
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The last point that I'd like to make is that, in fact, society does accept
risks. You know, if you stop and think about It, life Itself is very, very risky.
But you just have to consider what the alternative is, and to me the alternative is
not very satisfactory.
I don't know how informative I've been and maybe I have lectured at you
but with that, at any rate, I'd like to close. If there are general kinds of questions
or philosophical questions, I would be glad to deal with them today; if they deal
with technical questions, I would rather have an assortment of experts answer
these the day after tomorrow.
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TOWARDS A NEW PERSPECTIVE ON PESTICIDES
Henry J. Korp, L. L. D. *
I feel very encouraged about the sessions we conducted earlier, and as
I stated this morning, I feel we have shared a great deal together. While Jim Agee
could not be here himself, he asked me to express to you all his appreciation for
your participation in this fine effort to understand and support one another.
When we talk about the long-term environmental effects of pesticides,
and the potential threat to our resources posed by such effects, I hope we do not
imply that this Agency is concerned solely with the problems associated with
pesticide use. As I mentioned this morning, we are very interested in the whole
environmental situation, in recognizing the attributes as well as the drawbacks
to pesticides use. The quality and quantity of our food and fiber, the effectiveness
of disease vector control, the sanitation in our homes — pesticides play a vital
part in these areas which are important to all of us. The advantages and
necessity of pesticides cannot be disputed, and we in EPA are most cognizant of
the tremendous role pesticides have played and will continue to play in contri-
buting to man's well being.
But we have learned, too, that the past decade has offered some sobering
lessons about the ultimate effects of many products on our supposed prosperity.
Certainly, there has been a significant public awakening to the potential of
pesticide residues for remaining in the environment, for traveling far from the
site of original application, and for accumulating in the food chain. Our society
wants, it demands, that the government protect its interest in regulating pesti-
cides so that the benefits of pest control will not be sadly balanced by an ultimate
*Deputy Assistant Administrator for Pesticide Programs, U.S. Environmental
Protection Agency
Preceding page blank 109
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environmental tragedy. We thus believe that our past and future responsibility \
to the public is dual: to ensure that essential pesticide tools are maintained and j
to ensure that the benefits provided by these tools are not gained at the expense
of more valuable resources. If
' ' ' ' ' - 1'
In chatting with many of you today, I have found that some of the basic i
functions of the Agency which we take for granted should be better explained for ;
the benefit of those who are unfamiliar with the "nitty gritty" of our operations.
So, with the indulgence of those of you who are thoroughly familiar with our
procedures, I would like to take a few minutes to explain a bit more about the
registration process.
As I mentioned this morning, to obtain registration a manufacturer must
submit data to EPA to show that (1) the product would be effective for the intended
purpose when used as directed and (2) label warnings and cautions when followed
are adequate to protect man, livestock, wildlife, and the environment. Data
submitted to EPA is carefully evaluated by a staff of scientists to ensure that all
the criteria for registration are met. Pharmacologists review a proposed
registration to determine that the product will not pose a hazard to health when
used as directed and that the warnings on the label will prevent harm when ^
followed. Chemists review the application from the standpoint of the chemical i
composition and the compatibility of the mixture. Entomologists, weed control •'
specialists, bacteriologists, plant pathologists and physiologists, nematologists, \
and animal biologists study the application from the standpoint of their particular '
areas of competence. They determine how effective a pesticide would be
against the pests designated on the label, and whether or not the product would
cause undesirable side effects on the applicator or environment. No product is
registered until our requirements are all fulfilled. How does the consumer
know that a product has been registered by this Agency? All registered products
must bear an EPA or in the case of older products, a USDA registration num-
ber on their labels.
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I'd like to briefly point out several of the differences between the old Act
and the amended Act which will give you a good idea of what improvements have
been made in the regulation process.
First, ALL pesticides will be regulated under the new Act. The old
FIFRA required only the registration of products intended for interstate shipment.
Secondly, the new Act provides that pesticides will be classified for
either general or restricted use. Under the old FIFRA products were registered
or not registered, period. As soon as the general-restricted provision is
implemented, those products which we determine may cause an unreasonable
adverse effect on the applicator or the environment wilhout additional regulatory
restrictions will be classified for restricted use. Those products so designated
may be used only by certified applicators or subject to such other restrictions
deemed necessary by the Administrator of EPA. Thus, the most potentially
harmful pesticides — the ones in the restricted category — may be used only by
qualified individuals. We believe this provision will certainly guard against
pesticide accidents or improper application.
Thirdly — and this is a very significant change — pesticide misuse is
now a violation of the law. Under the old Act, we had no recourse when a
registered product was used in variance with label directions and precautions.
Now such misuse is subject to civil and criminal penalties.
The final provision which I shall mention is that the Act will afford
the public a greater opportunity to participate in the decision-making process
of this Agency. We will be publishing notification of applications for registration
of all new chemicals or changed use patterns, proposed regulations, and other
items which will allow opportunity for public consideration and comment.
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The new provisions of the Act are being implemented as regulations.
The new sections must be all effective by October 1976.
Many people ask, "What about the food I buy in the market? Am I not
subjecting myself and my family to pesticide residues which could be harmful ?"
Well, EPA is extremely concerned about ensuring that food offered for sale to
the consumer will not bear harmful pesticide residues. This Agency thus
establishes a tolerance or grants an exemption from a tolerance for all
pesticides which are to be used on food or feed crops under the authority desig-
nated by the Federal Food, Drug, and Cosmetic Act. A tolerance is the amount
of pesticide residue which may remain on or in the treated commodity when
marketed. Tolerances are not established by EPA until the pesticide manu-
facturer submits data to show that (1) the pesticide will not result in residues
exceeding the proposed tolerance when used as directed and (2) the proposed
tolerance level is safe for human consumption as demonstrated by toxicological
tests.
To ensure that residues in foods offered for sale in the marketplace do
not exceed the established tolerance, the Food and Drug Administration continually
inspects agricultural commodities intended for sale to ihe public. In addition,
the Department of Agriculture inspects meat and poultry for such residues. If
any food is found to have residues in excess of the legal tolerance, such food is
subject to seizure and destruction. I may also add here that there is a large
margin of safety allowed when a tolerance is set; the permissible residue level
is actually well below that which would be expected to cause adverse health ;'<;
effects. The consumer may thus be assured that EPA, USDA, and FDA are :j
fully cooperating to protect the public welfare through the strict regulation and V;
enforcement of tolerances. . J: -
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In speaking of enforcement activities, I must not omit discussing the
means by which the Government addresses registration violations. EPA has an
Office of Enforcement which determines if marketed pesticide products are
conforming to the requirements of the Act. Special inspectors in 10 EPA
regional offices collect samples of products throughout the country which are
analyzed in EPA laboratories to make certain that the ingredients are true to
label claims and that the product is not adulterated with chemicals other than
those listed on the label. EPA scientists also make laboratory and field tests
on a regular basis to check the effectiveness of registered pesticide products
and conduct pharmacological tests to ascertain that safety precautions continue
to be adequate.
If a product is found to be in violation of the Act in EPA's tests, appro-
priate action is taken to ensure that the deficiencies are corrected. In a
minor violation, an informal notice to the company concerned may be sufficient.
More serious violations may result in a formal notice of violation, seizure of
the company's goods, or even prosecution of the violator.
Many people have asked me about EPA's attitude toward new pesticides
and pest management techniques. I believe our position can be easily stated:
We wish to encourage the development of new pest control methods which
are especially intended to increase selectivity and decrease potential harm to
the environment or non-target life. You have heard about the research into
biological controls — the work involving pheromones (chemical odors which
direct many insect activities), juvenile hormones (those hormones which affect
the maturing process of an insect), chemosterilants, sterilization by radiation,
bacteria controls, virus controls, and cultivation of natural predatory insects.
We stand ready to issue experimental use permits for such new activities and have,
in fact, already Issued one such permit for the hormone insecticide Altosld,
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which is being tested in 15 states this year. And EPA has made it no secret
that we are encouraging work in integrated pest management techniques. We
have, in fact, along with the Department of Agriculture and the National
Science Foundation, committed over $20 million over the next 3 years to inte-
grated control research.
We would also like to extend our efforts in educating the public about its
role in proper pesticide use in the days to come. It may sound simple to say that
people should read the label before using a pesticide product. Those who use
pesticides in their profession, such as farmers, are usually most careful about
strictly adhering to label directions. However, homeowners, who often do not
have the proper attitude toward pesticide poisons, are not as meticulous* Unfor-
tunately, many folks will re^.d only far enough to see what a product is supposed
to control and then go running about flinging the contents in their gardens and
homes. The consumer can do a great deal to protect himself and the environment
if he follows four basic steps:
1. Read the directions for use thoroughly. Use only the amount directed
at the place and time directed and for the purpose directed. Too many people
sadly have the misconception that if one is good, two are better. One car is v
'"%!;
good, two are wonderful. One tablespoon of concentrate weed killer is called ;
for, two will do twice the job. This is a risky misconception and has the ;t
•"•J-
potential for destroying the entity one is trying to protect. In short, using a fg
pesticide in variance with label directions is not only illegal, but may also pose |j
a danger to the user, people in the vicinity, other beneficial life, and environ- :?;
mental resources such as air, soil, and water. Sif;?
**•• 'jf^i-'1
2. Read the precautions. Precautions are introduced by one of three j||
signal words - CAUTION, WARNING, or DANGER-POISON. Those in the ?S
highest order of toxicity are accompanied by the skull and crossbones. DANGER- '*£
POISON denotes those products which are most hazardous, with those in the • ^
114 '4
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WARNING category less potentially harmful, and those in the CAUTION the least
hazardous. All pesticides warn the user to KEEP OUT OF REACH OF CHILDREN;
in fact, it is best to lock such products out of children's grasp.
3. Observe the ingredient statement and first aid statement, if supplied.
These are invaluable if an accident does occur. A copy of the label should always
be taken to the physician in such instances.
4. Store the product in a safe place and in the original container. Never,
never transfer a pesticide to a soft drink bottle or any other container, especially
one attractive to children.
In an effort to find out what can be done to improve labels, EPA contracted
with the University of Illinois to conduct a multlstudy devoted to finding ways to
make the pesticide label a better communication device. As a result of the
study, we held the National Labeling Symposium a few months ago to which we
invited all registrants to discuss the findings of the Illinois report. We hope our
seminar developed many means by which a manufacturer can make his label more
readable and attractive to the user. We have also contracted the University of
Illinois to conduct another study, this one devoted to investigation of the value of
non-verbal symbols (such as faces or traffic signs) on pesticide labels.
Our Office of Public Affairs offers to the public many publications
regarding the role of this Agency in pollution control and the role the concerned
citizen can play in this vital area. We have just issued a new pamphlet directed
to the consumer describing the regulations of pesticides; these pamphlets are
available for public distribution.
In closing, I would like tp thank you again for your interest in our program
and for helping make today a success.
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OVERVIEW OF WORLDWIDE PESTICIDE RESEARCH
Morris Cranmer, Ph. D*
Welcome to the second day of this symposium. I believe this day will
produce some conversation and insight into the problems before us. My name
is Morris Cranmer. I'm Director of the National Center for Toxicological
Research. The National Center is in Jefferson, Arkansas. Contrary to some
persons' opinions, we do not conduct mega-mouse experiments like in the
commercial. I want to thank Dr. Axelrod for making it possible for me to
participate in this program. I certainly have had a long-time interest in pesti-
cides research and our laboratory, hopefully, will impact considerably on some
of the dilemmas that are facing us in coming to grips with the problems of
safety evaluations, especially with respect to environmental chemicals which,
of course, include pesticides as a major class.
The National Center for Toxicological Research is a national resource.
Its original charter was constructed to be a mechanism by which various Federal
agencies could cooperate in problems which impacted especially on their regu-
latory mission. Currently the Environmental Protection Agency and the Food
and Drug Administration are jointly sponsoring the center; however, NCTR, as
a national resource, must also be responsive to the university community in
providing access to certain research opportunities that might not exist in the
parent universities, in stimulating graduate education in toxicology, providing
a mechanism for bringing distinguished foreign scientists to the United States to
work on special areas of toxicology, and to eventually provide an interface by
which the Industrial community can work hand in hand with the academic commun-
ity and the government community in solving some of these problems which are
*Director, National Center for Toxicological Research
Preceding page blank
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so important not only to our economy, our standard of living, and our health
but Indeed to the health of the world.
Our topic today is "An Overview of Worldwide Pesticides Research. ? What
might be included in pesticides research? Certainly pesticides research in-
cludes compound development, field tests, safety evaluations, prospective and
retrospective evaluations of the sociological, economic, and health impacts,
ecological consequences, and marketplace competitivenesses of pesticides.
We are fortunate today to have speakers to discuss each of these topics
from the vantage points of the United States government, the academic community,
and industry. We are especially fortunate to have several distinguished repre-
sentatives of the international community to add an absolutely essential perspec-
tive to our deliberations. The earth is a closed system and what we in the
United States do or do not do impacts extensively on the rest of the world.
Research findings, if correctly translated, are perhaps the commodity
most Immediately and directly applicable to all parts of the world's family of
nations. Research findings, both sociological and economic, and alternate con-
trol strategies peculiar to the United States, however, at times can and have been
tragically applied to other countries.
The paradoxical pursuit of the pristine purity of absolute safety for
synthetic compounds and the near passive acceptance of the consequences of
certain naturally occurring compounds is symptomatic of our current inability
to deal with the concepts of acceptable risks versus costs and benefits of control
strategies. Equally vague are differences in approaches to voluntary versus .^.
•??••.'•>•-:
involuntary risks and exposures. i^ifi
The attempts to solve a simple equation, including costs, benefit, and
risk, will be unsuccessful since the units are not equatable. A more appropriate £§|
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procedure will be the simultaneous solving of several equations with similar
units, with a final social synthesis.
I see in the program that we will continue discussing today and to-
morrow, the opportunity to foster the cooperation of all segments of the toxico-
logical community toward improving our regulatory approach to solving our
problems.
I would like to draw on two examples, not from the pesticides industry
and not from EPA, to avoid an outbreak of napkins being thrown at me, but from
equally relevant situations existing in the Food and Drug Administration, a
sister regulatory agency to EPA.
Examples that I might offer would include, for instance, cyclamate
and DES. If we might explore the cyclamate problem very quickly. Cyclamate
was a compound which, from the viewpoint of FDA, was an abused compound;
certain components of society used excessive amounts of this material. Certain
advertising practices promoted the use of this compound in extraordinarily high
quantities. Cyclamate was on the GRAS list, which is a peculiar situation which
does not require certain types of toxicological information to be provided as in
the registration of a new food additive.
The evaluation of cyclamate produced a toxicological controversy which,
in the opinion of the then current Commissioner of FDA, required the removal
of cyclamate from the generally accepted as safe list. This does not necessarily
mean that it said the compound is toxic. It simply means it can't be generally
accepted that it's safe, but indeed a controversy raged over this compound and
indeed continues today.
We have here an abuse of the compound. We have a toxicological
controversy with inadequate information to completely or unequivocally resolve
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this controversy . We had a legislative mandate which was inflexible. Here all
components of society interacted to produce a situation which resulted in a
legal resolution to a problem that, hopefully, science could have impacted on
had the information been forthcoming in a timely way.
What was the result on the health of the nation as a result of this de-
cision ? There was a considerable shift from the use of cyclamate to saccharine.
Now indeed the safety of saccharine is in doubt. The question before us is
"Was the public health interest served by concentrating the exposure of our
population to a single compound or a few compounds from various compounds
that might have been available?" In other words, a suggestion that a considera-
tion of a regulatory impact might have been beneficial. What total risks, in
other words, are Involved?
Now let us review the DBS controversy. Here Is a situation which Is
indeed controversial. We had the Bureau of Drugs, which can apply special risk-
benefit type of analysis, approving the day-after pill, which would result in 5
dally 50-mllligram treatments with dlethylstllbestrol. We had the Bureau of
Poods responding to another component of the same law, suggesting that the
Commissioner remove the dlethystllbestrol approval because of certain residues,
two or three parts per billion, of dlethylstilbestrol In two or three percent of the
livers that were analyzed.
If one does a quick calculation of how much liver you would have to eat
in order to equal one day-after pill regime, It comes up to about a million or so
pounds of liver. On the surface there seems to be to me a slight discrepancy
between the risk and benefits that might be applied through these two parts of
the same law.
What could be the side results of this particular decision? As you
diethylstllbestrol was used to promote the growth of livestock animals. There's
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some debate as to the efficiency of this growth-promoting process; however, let's
say that one-eighth of the soybeans that would be necessary to be consumed would
have been saved if dlethylstilbestrol was still used.
The Congressional Record contains testimony that says it cost the
population of the United States about a half a billion dollars directly because of
this decision. Half a billion dollars is roughly the equivalent budget of the
National Cancer Institute. I wonder if the benefit from the research of the
National Cancer Institute is equal to the risk that was eliminated by the banning
of diethylstilbestrol ?
However, when we eliminate diethylstilbestrol, we increase the con-
sumption of soybeans internally. That makes less soybeans available for export.
When there are fewer soybeans available for export, there are fewer hungry
people in other countries that are going to get the soybeans. In addition, short-
ages adversely affect our balance of payments.
As you know, our balance of payment impacts on the ability to buy
expensive foreign oil which is low in sulfur. More oil which is higher in sulfur
requires either scrubbers to remove the sulfur or more sulfur dioxide in the
air. One might conclude that the people in Los Angeles are going to have more
emphysema because of soybeans in the Midwest.
It is an interesting web of involvement that one might begin to develop.
How about the diethylstilbestrol situation ? Where can we point the blame ? The
farmers misused the compound. Certain misuses were identified. There's
no doubt about that. There were legal arguments that got into the situation as
early as 1958 and even before that, which further complicated the situation.
There's no doubt that diethylstilbestrol is a human carcinogen, but it
was massive doses of the compound which produced this effect. It is also equally
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clear that the Bureau of Drugs considered it to be safe for day-after pill treatment
under proper supervision. We had only incomplete toxicology provided either by
the Federal government or by industry. The controversial dose response studies
that were done by Gass are yet to be repeated or explained. The impact of
viruses in terms of the development of mammary cancers is yet to be completely
explained. There was a regulatory error by the Food and Drug Administration
which was reversed by the courts and then, of course, there was the law that
we had to respond to which was basically an all or none philosophy. As I see it,
each component of society was involved in this particular dilemma; again I think,
an example of where we might begin to work together.
In short, all or none, nonscience, no choice, simple solutions, and
adversary legal atmospheres are rarely best for society. I might ask whose
risk, whose benefit, whose cost? I think the speakers later on this morning will
address this. From conversations with them yesterday and last night, I know
that a number of the points that they will bring out will be provocative.
Unfortunately, our approach to the accumulation and dissemination of
• »
additional data has been no news is good news. Take DDT for example: We
have no adequate mechanism for establishing the relative significance of a mouse
hepatoma and the exceptionally expansive data base on the safe human use
experience.
We must, in my opinion, construct a concert of mutual trust, cooperation,
and understanding if we're to speak to these problems, and indeed this symposium
:/';
is to address mechanisms to approach this problem.
^."^
Paramount, I believe, in this process is the promulgation of strategies |
which encourage and reward the collection of data by all sectors of the community iI
relevant to the protection of health and of the environment. And this strategy '$
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must accept that the process of collection of this data will include the discovery
of some adverse effects while at the same time providing a better total under-
standing.
I think that it is completely obvious to everyone in this room that our
greatest national contribution is not our jet planes and not our computers and
not our ability to get to the moon, but our renewable natural resource, agricul-
ture. When one considers if you added up all the cancer deaths that have ever
occurred in the United States from the time there has been a United States, it is
less than those deaths which can be attributed to malnutrition and starvation in
the world each year. A perspective is definitely needed.
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WORLDWIDE PERSPECTIVES
OF PESTICIDE RESEARCH
Frederick Coulston, Ph. D. *
Mr. Chairman thank you very much. I'll try to be provocative but I don't
feel that way so early in the morning. Our good friend Dr. Axelrod and other
people, it's a pleasure to be here. I was given a topic of which I know a little,
or should say I know little about it, but we'll try to develop the topic.
I have prepared nothing formal and so we will just have some fun and if
you get really provoked, just raise your hand and we'll have a little discussion
and that might be more fun than looking at a few slides.
Yesterday I counted the use of the term "benefit-risk ratio relationship"
42 times and then gave up. It was said 42 times and I had the impression that
some people knew what it meant and some people didn't know what it meant. I
think I'll take just a few minutes before I start and let's play with that phrase a
little bit. Then I'll get on to this world prospect topic, but it is part of the total
picture.
Risk to what? It's a risk to a hazard and if this is not considered in this
context, then you don't have anything but words. If I stand here and tell you I
have a compound extremely useful to man, that we must use it, but that it is one
of the worst teratogen I have ever seen for rats and mice, what would you do?
Would you allow such a compound to be used? But if I also tell you that for dogs
and for monkeys and for man, there is no evidence that it had ever been a teratogen,
then what would you do? You see this is the concept, the true concept of risk to
hazard. How does the animal data predict to man and which species is best.
It's a hazard obviously to mice and rats. The compound I'm talking about
* Director, Institute of Comparative and Human Toxicology, Albany, New York.
125
Preceding page blank
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is aspirin — common, ordinary aspirin that I'm sure a third of the people in this
room took this morning.
I could develop this further but the question of cyclamate came up this
morning. I don't want to be on a pesticide program talking about drugs and food
additives. That wouldn't be right, but yet this is another perfect example of what
I am saying. Cyclamate was never used as cyclamate. In use, it was always
mixed with saccharine; so if cyclamate is declared and banned as a carcinogen,
the fact is that we never did prove whether cyclamate or the little bit of saccha-
rine caused the problem. The point is, we then switched to saccharine. Now
saccharine is accused of producing tumors. What do you do now with saccharine?
In a similar fashion about diethylstilbestrol, just let me add this. The
reason that the FDA finally tried to de-list it, was because a substitute was avail-
able. I think this is a very important point; that you don't try to ban something
useful and needed or restrict its use, unless a very substantial, good substitute
for it exists, so that you don't hurt agriculture or the people or the economy.
There is a good substitute for DES approved by FDA; these are new non-steroidal
estrogenic lactones, which have been very successful in replacing diethylstilbestrol
in most cases.
Now to come back to this benefit-risk business. It's a widely overused
term. I first heard the term used in 1952 by that grand old man, the father of
modern toxicology, Arnold J. Lehman, who was at the Food and Drug Administra-
tion at the time. He used to talk to me about this benefit-risk concept. Actually
not enough credit is given to the role that the Food and Drug Administration played
in those early days when we were shaking off the concepts of pharmacology and
biochemistry and betting to grips with the multi-disciplinary approach to the
problems of safety evaluation, which included pathology, excretion and distribu-
tion of the chemicals, etc. Such great men as Leahman, Fitzhugh, and A. A. Nelson,
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understood the multidisciplinary approach which developed modern toxicology.
They knew that the benefit-risk relationship depended on a good understanding of
the hazards involved in terms of the intended use of the chemical. In other words,
they knew that the risk must justify the hazard.
Now I'm going to switch to the subject that I'm supposed to be talking
about.
In the world today, because of regulatory decisions that have been made,
the research in developing new compounds worldwide as pesticides has changed
dramatically. When the so called "chlorinated hydrocarbons" were in trouble,
such as dieldrln, DDT, the big, major research companies in the world made an
obvious decision. They said, we cannot work any longer on substitutes for DDT
or on other chlorinated hydrocarbons because even if we found a good one, we'd
never get it through a regulatory agency or, the extremists among the environ-
mentalists would hound us to death because of the possibility of build up in the
environment, disregarding any good benefit to risk relationship for the intended
use of the chemical.
Consequently, there is not, to my knowledge, a major chemical or pharma-
ceutical company in the world working on true substitutes for DDT or its
related compounds. To me this is a tragedy because, as is being learned today
in research, these substances are not so persistent in our environment. The
work that's being done today in Germany in Professor Korte's laboratory clearly
indicates that under the conditions of let's say 50,000 feet up in space, DDT,
dieldrin and other compounds, are completely converted to carbon dioxide and
water in three weeks, if placed in an environmental situation that mimics the
atmosphere. On land it requires about three times as long.
In other words, they have made equipment in which they have exposed the
various compounds to ultra-violet light. Photo chemistry is not a new science.
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It's been known for a long time, that some chemicals change drastically when
exposed to light, air, temperature and humidity. Korte and his colleagues have
shown that the rate of change of DDT to carbon dioxide and water is about four
percent a week when the DDT is placed on a plate and exposed to ordinary tempera-
ture, light, and humidity.
In other words, it would disappear eventually. Now someone very wisely
said yesterday that something must happen to DDT because we're not all full of
DDT. It is well known that DDT disappears from the surface of the earth and I
think now we're beginning to understand some of the reasons why. Under certain
conditions, it is possible for DDT to disappear as carbon dioxide and water.
This is research that LJ in process and was presented in part at the
IUPAC meetings in Helsenki. I think many concepts about the bio-degradeability
of chlorinated hydrocarbons will be changed. The late Henry Hurtig clearly
demonstrated that some of the so called bio-degradeable OP compounds are not
so bio--iegradeable. Some parts of the molecule persists for long periods of time,
sometimes even as long as we thought DDT did. So what is the trade-off here?
Now ril show you a few slides.
What I'm trying to get across to you is that in this whole concept of
research, we should not be limited to the carbonates and to the OP compounds.
Hopefully somebody someday will make a break-through and find a new type of
chemical moiety that would be beneficial and as harmless to man as are DDT and
dieldrin.
I've talked to a lot of people recently about the attractants and one of the
leaders in this field, recently in Helsenki, told me that to use them alone is hope-
less. The attractants will not do the job unless you use an insecticide with them
such as DDT. I'm not advocating a return of DDT, please. I agree wholeheartedly
with the WHO statement made I think in 1969 at the joint FAO-WHO committee,
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that DDT should be phased out as soon as an adequate substitute can be found. No
one wants to use a chemical that may harm some aspect of the fauna of the world,
and from a toxicologist's view point, we don't know what the storage of DDT in
our body means. Is it good for us or bad for us? There is no evidence either
way. There's no argument about this, but the trade-off is the question — the
benefit-risk is the argument.
Now this leader in the field of attractants said to me, if only we could use
a little DDT with the attractants, it would make a great difference. If we could
take a plot in the forest, say one mile square, and attract the gypsy moths to the
plot and just put the DDT on that plot, then we possibly could achieve our purpose.
If you could strategically place these attractants plus the DDT in plots throughout
the forest, you might accomplish the control of the insect without spraying the
forest completely with DDT. These plots could be observed and studied from all
aspects. You can even cover it with a screen to keep the birds out if you want.
In other words, this idea of using conjointly, certain pesticides with
attractants or juvenile hormones is a good one and the concept should be pursued.
I was told that he could not get permission to try this concept. He could
not get permission to use DDT. Use your own judgment. He and his colleagues
should be given the opportunity to try their ideas because I believe it would help
solve a difficult problem, threatening our great forests.
So in essence, I've told you about some of the pesticide research going on
In the world. There are traps and all kinds of other devices. There are the
viruses. There are the bacteria. There's no great hope that these will do a large
v
job. They may be useful in very specific areas but speaking, worldwide, it's
hopeless to even conceive of the use of these systems at the present time.
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Certainly in a country — in the developing countries, DDT still will be the
pesticide of choice for a long time, provided there hasn't been a development of
resistance. If they can for 30 cents, take care of about 30 hectares of land, they
are going to use DDT because they have to grow food as economically as possible.
If they use DDT, it's going to come right back on us. You've got to realize what
you're doing when you say, let's restrict this or ban that. You've got to watch
where the winds blow, very literally.
So much then for the worldwide research in the few minutes I have. I
wish I could have gone into more detail because it's a problem very dear to my
heart. The biggest problem with the OP compounds right now, is the question of
demylination, or in general, neurotoxicity. Some of the OP compounds are com-
pletely safe when used as directed, others are not. In our institute in Albany, we
have a very extensive program just trying to figure out why demylination occurs
with certain OP compounds and not with others. This is not federally supported —
it's not government supported. It's a case, where industry on its own has said,
we need to solve this problem, help us out. This type of support for research is
both desirable and commendable.
What is the problem worldwide? Let's have the first slide.
SLIDE 1
TABLE IV. WORLD PRODUCTION OF ORGANIC CHEMICALS. 1970 (4)
Grind total (10> I)
ORGANIC CHEMICALS -
Manufactured
Solvent!
Detergents
Pesticides
Gaseom base chemicab
Miscellaneous
1950 1970
7 63
WORLD PRODUCT10I
(10*0
10
1.5
1
7
1985 Release into environment. 1970
250 20
M
Natural sources (10* t)
Methane 1600
Terpene-type hydrocarbons 170
Lubricating and Industrial oils 2-5
130
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This slide (1) shows the worldwide production of chemicals as of 1970. You
can see the grand total here in metric tons, ten to the sixth metric tons, and this
would represent the amount that probably gets back into the environment. This is
a guess, but a very —• very substantial one made by people who know what they're
doing. These figures are all sophisticated guesses too, but we have an idea of
approximately how much solvents are made, and detergents, and notice that the
figure for pesticides represents a very small amount of chemical as compared to
the other organic chemicals. Also, on this slide is a very startling figure to me.
The terpins hydrocarbons that are formed from trees are greater than the total
amount of pesticides used, by many times. This is more of a problem worldwide
than worrying about relatively small amounts of pesticides. If I were an EPA
research administrator, I'cl be putting my money on research aimed at finding
out what these terpins do biologically because they are one of our natural problems.
SLIDE 2
TABLE v. ORGANIC CHEMICALS WILL REMAIN THE LEADER
Chemical product classes: Estimates for 1970. 75. 80
made in 1969 (SJ
Shipment!. 10' US dollars (1969)
Key chemical product classes
Chemical and allied product!, total
Alkalies and chlorine
Industrial gases
Industrial organic chemicals
Industrial Inorganic chemicals
Plastics and resin material]
Synthetic rubber
Man-made fibres
1970
54. 4
0.86
0.71
8.29
5.13
4.81
1.25
3.76
1975
78.8
1.25
1.05
13.26
7.64
7.03
1.67
5.71
1980
114.4
1.86
1.55
20.95
11.46
10.41
2.29
8.64
131
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In this second slide, we have tried to project into the future what may
happen in 1975 and 1980 to the total production of organic chemicals, based on
1970 figures. These are slides that were prepared for the International Atomic
Energy Agency and they're based on extremely good information. Here again,
you can see that the industrial organic chemicals are the ones that will continue
to increase. The total production of everything in organic and allied chemicals
will go up very substantially, all in this decade.
SLIDE 3
TABLE II. GLOBAL CONCENTRATION OF THE ORGANIC
CHEMICALS, IF UNCHANGED AND DISTRIBUTED
EVENLY OVER LAND SURFACE
Land surface of the earth 140 x 10' km'
Volume of oceani 1.3x10'km'
Weight of the atmosphere 5.1 x 10B t
Total organic chemicals production (1973) ~ 100 x 10* t
Basis of calculation: no breakdown, dispersion of total amount on or in one medium only
Dispersion over total land surface 100 mg/m' (~ 7 kg/ha)
or with penetration Into 10 cm thick soil layer 2. S ppm
Dispersion in ocean volume 0.8 x 10"4 ppm
or in 1 m thick layer 0.3 ppm
Dispersion in atmosphere volume 0. 02 ppm by weight
Slide 3. Here is the slide that I think is the most fun because it tells you
a great deal and gives you a chance to speculate. The total land surface of the
earth as shown in this figure is 140 times ten to the sixth square kilometers.
These are synthetics; organic chemical production, 1973, and no breakdown, no
dispersion of total amounts or anything else. This is just calculating what would
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happen if you just took the total production and spread it out on the earth. It
comes out to 2.5 parts per million,: if you have a ten centimeter, fixed soil layer.
Now I'm supposed to talk about world problems, so here is some of the
problem. In the ocean volume, a one meter thick layer, it will come out to . 3
parts per million, and dispersion in the atmospheric air, . 02 parts per million.
SLIDE 4
TABLE III. GLOBAL CONTAMINATION FROM PESTICIDES.
NITROGEN FERTILIZERS AND. FOR COMPARISON,
ORGANIC CHEMICALS
Land surface of the earth
14 i 10' ha
Agriculture (a)
Pastures (p)
Foresu (f)
1.4 » 10' ha
3 x 10' ha
4 x 10' ha
Input to soil per year
(no conversion, no evaporation'or leaching)
Pesticides
Nitrogen fertilizers
Total organic
chemicals
World production
(10s t/yr)
1
10
100
kg/ha in are
locally
2-4 0
70 3
1
l of use
globally
12 (a/p/f)
4 <•/?>
KO (a/p/f)
When distributed over
total land surface
(kg/ha) (mg/m1)
0.07 7
1.1 no
7.0 700
Slide 4. I Just want to give you some idea of what we're talking about.
These are the problems. Now, if you take pesticides as used today and talk
about global contamination from pesticides, you come up with this figure. If
you assume a land surface of agricultural lands, pastures, forests as these
figures here do in hectares, and if you also consider that no conversion of the
chemicals happened, then you find if you come down to this part of the slide that
fi
the world production of organic chemical 100 x 10 metric tons a year in total
133
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6 fi
and 1 x 10 is pesticides, and 15 x 10 nitrogen fertilizer. Now these are figures
that are kind of fun.
If you go to this column, you will see that when pesticides are distributed
over the total land surface, you come up with a figure of seven milligrams per
square meter of land surface, or, putting it the other way, .07 kilograms per
hectare. Nitrogen fertilizers are much more, while the total organic chemicals
produced are, in general, almost another order of magnitude.
So the pesticide problem is not really so great as compared to the total
amount of chemicals that we are actually putting on the earth each year. In my
opinion,, with the research that's being done now in many laboratories, the pesti-
cide safety problem of residues can be very soon explained on the basis of bio-
degradeability. And remember, these figures are presented with no conversion,
no evaporation, no leaching, so that we're talking about the best total figures of
use that can be put together.
SLIDE 5
EVOLUTION OF ANIMAL EXPERIMENTATION AND
PREDICTABILITY OF TOXICITY IN MAN
I. A rot or two. on odd rabbit, o f *w mice
2. Numbers of rot* increased via statistics; dogs com* in, rabbits
out, cots score*
3. Further increase in numbers of rats, also dogs, also mice
4. Mar* species, monkoys. marmosets, chimps, guoil. pigs, fowls
9. Tim* of testing incroasod. 10 days. 3 months. 6 months. 2 years.
7 years. Ufa spans
6. Multigenerations tests. Corcinogenesis. mutigonesis. teratogenesis
7. More strains of many species, inbred, outbred
6. Count the dead, weigh the organs, examine histologicqlly
9. Biochemistry, cellular and subcellular effects. Radioisotopes
10. Trial by ordeal in man
134
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Slide 5. Having briefly defined what the world problem is — having talked
a little bit about benefit-risk, let me just review with you very briefly what
decision-making has to do with the benefit-risk ratio. This is a history of toxi-
cology. It begins in 1940.
In 1940, it was possible to get a drug or a food additive cleared at the
Food and Drug Administration in Washington, D. C., just by studying the chemical
in a few rats, a few rabbits, an occasional dog, with a little pharmacology. A 30
day experiment in rats was sufficient and you got clearance as to safety of the
chemical. Not efficacy. I'm only talking about safety evaluation here.
Then we soon learned, beginning in World War II, in the 1940 - 1946 period,
that this wasn't sufficient. So, we began to increase the numbers of animals. We
used statistics, we used more dogs. We couldn't even get a cat in Chicago, where
I worked. They were all being used up by research laboratories of one sort or
another. We Increased the numbers of animals, because of the lack of our assur-
ance of safety. We began to use all kinds of species; as early as 1935 — I was
using rhesus monkeys for these kind of toxicity studies and, during the war,
they were used extensively. Now we have the chimps and other non-human pri-
mates.
Then the uncertainty of these procedures led to this marvelous extrapola-
tion that if two years isn't enough to decide whether it's safe, let's make it seven
years, let's make it ten years; so we kept increasing the number of years and now
you finally have life span studies of animals. You do multi-generation studies and
carcinogenicity, mutagenic, teratogenic experiments. We use strains of strains
and strains of species. We in-bred them: we out-bred them. We count the dead
ones and we weigh the organs and we examine them. We do bistro-chemistry
and electron microscopy and bio-chemistry. Now we're in the insides of the cells,
studying the sub-cellular organelles. But, in the final analysis, you've got to go to
135
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man, because we just don't know how to predict completely from animal data to
human response. We're learning.
SLIDE 6
PREDICTABILITY SCORE OF DRUG REACTIONS
FROM ANIMAL STUDIES
REACTION
PREDICTABILITY
Direct toxteity to on orqon system
Safety factor
Intended drug action
Undesirable (wrong organ, biochemical
Hemotytic reaction*
Drug or metabolite storage
Yes
Limited
Yes
Yet. through we of
large doses
Usually
Yes
The next slide (6) shows you the kind of things we can predict and this is
very important in considering your benefit-risk ratios.
Ordinarily you don't go to man to find out if the animal tests were right or
not. In many cases, we do go to limited studies In man even with pesticides and
food additives to make sure of the safety evaluation based on animal studies.
Remember my good friends, you put 220 million people at risk based on animal
data. This would never happen with a drug, of course, because you do some
human trials. Your information as to predictability must be even better than
with drugs, and unfortunately, it often isn't. So what do you do? That's your
136
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dilemma. We try to figure out something to do; but we'll help.
The point is, we have a very good record in predicting these sorts of toxic
effects; direct toxicity to an organ system, safety factors, intended drug use,
undesirable long range organ effects, which is quite common in carcinogenesis
studies, hemolytic reactions and then the metabolite storate, and so on.
SLIDE 7
PREDICTABILITY (cont.)
REACTION PREDICTABILITY
Individual humon rooctivity Mo
Pf««Ki«ting potholoqlc ttot* producing od»tfM tfftct Mo
lotrogtnic offocts No
Undosirod «ff«ct« not drug rolatod No
Undosirod action requiring contributing iatroganic~
factor No
iHtOf fOTOIICO With d0tOR80 ItltClMMMIV
Intorfaronco with nutrlont obtorption
Toxic tfftct on fetus
Alltrgy
idiosyncrasy
No
No
No
No
No
PnotoMmttitation No
Slide 7. But where we are almost completely lost is in all of these things
I've listed; individual human reactivity. Remember this is predictability from
animals to man and here's where we can go wrong. We don't know anything about
pre-existing pathologic states producing adverse effects. We don't use sick
animals in our animal studies. We have very few real models of disease anyway,
in most instances, except in the parasitic type infections and micro-biological
infections, in general. We don't have a good model for high blood pressure and
137
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how do you know the pesticide isn't going to affect high blood pressure. You see,
we don't have a good model so the toxicologists have to worry about this a little
bit. Eventually the pharmacologists, I'm sure, will help us out. The key thing
down here is toxic effect on the fetus.
We have no certain way yet to predict teratology from animal to man. We're
hopeful that the monkey model helps a little more than most studies. I remind
you that thalidomide never affected the rat or the mouse, completely worthless,
and if we had stipulated the use of rodents in guidelines, we would have missed
the danger of thalidomide anyway. Be very careful with your guidelines is all I'm
saying. In fact, if I give you any advice this morning, do not make guidelines that
are too detailed and restrictive.
Every one of those companies that is sending you material, have experts
who know what tests to do; then you can judge whether he did it right or not. You
don't have to have guidelines that are so restrictive they stop the development of
scientific thinking. I often go abroad and I find in some countries that they are
using guidelines that the FDA put out in 1954 that are wrong by today's thoughts.
Guidelines should change almost every day, anyway.
If I tell you now there is no test for mutagenesis acceptable to everyone, to
most scientists that I know of, including those at the FDA, how are you going to
establish guidelines then for mutagenesis, except to say, please fellows, do some-
thing. Let us see what you do. Maybe they'll develop a new test.
What's the guideline for teratogenesis? Are you going to ask for three
generation, four generation? I don't know. As far as specific guidelines for
carcinogenesis, forget it. Last week in Saratoga — and there are at least four
people in this room who heard the discussions — some of the most eminent path-
ologists and cancer research men in the United States said, throw the mouse test
out. It's essentially worthless in predicting carcinogenesis to man. If you want
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the names of the people that made this statement, I'd be delighted to give them to
you later; but their remarks will be published, anyway.
Now I'm not suggesting to throw the mouse test out. I'm trying to say,
understand the mouse, but don't base decisions on whether a chemical produces a
hepatoma only in a mouse, but rather on the fact that it does or does not in a rat
and in a dog and in a monkey and in man. If the hepatoma only occurs in the mouse,
you've got a problem.
The whole problem with the carcinogenesis of chlorinated hydrocarbons in
mice literally depends on the differences between strains of mice. In some there
may be established a no effect level and a dose response relationship. In 1969,
some in the audience will remember that the WHO-FAO group on pesticide residue
made a statement that we could have a no effect level and a dose response curve to
a teratogen.
Many members of that group agreed that this statement could also apply to
a carcinogen. One man objected strenuously, and by the way, that one man now
has changed his mind and he agrees with what I am saying. We did say, however,
in '69, that more research must be done to establish whether a no effect level can
exist for a carcinogen and whether a dose response curve is possible. The answer
is that with DDT, with phenobarbital, with dieldrin, with mirex, this is so. If I
could just leave this message with you, I'll be happy. If you take a low level of a com-
pound which may only cause a hepatic-parenchyma! cell to hypertrophy — to get
bigger — you exercise a muscle, it gets bigger, drink a lot of salt or a lot of
water, your glomerular cells get bigger, you eat a lot of fat and your hepatic cells
get bigger. In other words, this is a normal, physiologic process of how the body
handles a chemical and metabolizes it, passes it on in a form that it can be excreted.
But if you keep pumping into the liver day after day, a large amount of chemical
then the cell cannot handle it and the cell gets bigger — and the cell gets bigger —
and the hepatic liver cell may now be two to three times its normal size, and you
139
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keep pumping the chemical in, what do you expect? The cell will die.
Now either the cell is replaced by another normal hepatic cell or it may be
replaced by an abnormal one and hyperplasia may occur. When you get hyperplasia,
you can get hepatic nodule formation, and you can get true carcinomas, but why
shouldn't you expect this ? What darn fool would keep pumping chemicals to the
cell at high levels that the cell cannot handle. If I had a big balloon and I blow air
in it and I fill it to its normal size and then I blow it twice the size and then I try
to blow it four times the size, it will burst, and that's exactly what you're doing
when you're pumping in these chemicals during these long term, life-time studies,
keeping the dose constant at high levels. You say, oh eureka, I found a tumor.
Why shouldn't you find one ?
I heard a prominent controversial FDA scientist on television this morning.
She has just written a book stating that many common food additives should be
banned. She said there are many people who believe one molecule will cause a
cancer. Well this may be true. A few molecules could cause a cancer, if it's a
primary carcinogen, but the chlorinated hydrocarbons we're talking about, DDT,
dieldrin, and phenobarbitol, are not primary carcinogens. At low level dosages,
a no effect level can be established; nothing happens in the animals, even in
highly susceptible mice, that's the point; a no effect level and a dose response
relationship can be established.
Now if I had to consider a nitrogen mustard, it could very well be that
100 molecules could cause cancer because these are highly potent carcinogens.
You must recognize you don't throw everything in the same pot and say, oh I got
a tumor, therefore it's cancer. This is not the correct way to look at it. You
must separate in your thinking those chemicals that change cell structure and
identities from those that mechanically are stored in excess in cells.
140
-------
I'm going to go very fast on the slides because I'll try to finish in two
minutes.
SLIDE 8
Dietary Intake of Pesticide
Residues relative to a.d.i
aldrin * dieldrin
0.6
heptachlor « heptachlorepoxide /16
tindane
D.D.T+ D.D.E* D.D.D
dlcofol
car bar yl
malathlon
parathion
dlazinon
inorganic bromide
Vsoo
VIA
'/250
1/20
Vsoo
Vsooo
Vzooo
0.4
Duggan, Lipscomb 1969
This slide (8) presents a very important point I want to make. This is an
old slide of our good friend, Dr. Dugan, Many people object to these kind of
calculations based on the ADI and the amount of chemical that's found in the bread
basket. But somebody talked about it yesterday and I thought there was a point
to be made; here is such a slide.
As far as I know, the ADIs of any pesticide in food has never been exceeded
except for one year I think somewhere around this time (1969) or a year after,
when the residue of dieldrin equalled the ADI in the market basket survey, but to
my knowledge, it never has been exceeded. Now, if this is true, why are we
141
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paying all this attention to safety -- why are we so concerned about a lot of these
pesticides that are being used properly for their intended use in agriculture ? If
they're being used properly, then this is the outcome, our food is safe. If our
food is safe, then maybe we're spending too much of our effort and time worrying
about some of the things we heard about yesterday. Maybe we have reached the
point of thinking that safety depends on. a safety overkill with hundreds of times
safety factors; safety factors for what - mice or men!
As far as the public is concerned, men like Dr. Lu (WHO) arid Dr. Turtle
(FAO) and the people of the FDA have their jobs. We mustn't forget that over the
years they protected all of us. This is all I'm trying to say. To my knowledge,
we have never exceeded ADIs for pesticides in the bread basket studies done in the
USA.
Question: Are those average figures or maximum?
Mr. Coulston: No, these are average I'm sure, but it doesn't matter. Go
on to the last slide. (9). Now here — here's an example of the whole benefit-risk
relationship.
SLIDE 9
"I cortainly will not tike a bite. How do I know it lint hill of
chlorinated hydrocarbon!, btnzant hoiachlorld*, or organic phoiphatn."
142
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This is Adam and Eve in the early days of mankind. Now Eve offers
Adam an apple. Now he must decide the benefit risk relationship. What would
have happened to the human race if he had answered as in the caption, "I certainly
will not take a bite of the apple. How do I know it isn't full of chlorinated hydro-
carbon, benzine, hexachloride, organic phosphates, tec." I think this kind of
sums it all up. Thank you very much.
DR. COMMONER: I'd like to make a few comments on a number of speci-
fic points that have been made by Dr. Coulston and then make some general
comments.
First, let's take the slide that dealt with the daily intake of various pesti-
cides and as I recall, the highest value relative to the acceptable level was 0.6.
I asked Dr. Coulston whether that value was an average and apparently it is. What
does that mean? That means that among a large population in which the average
is six-tenths of the acceptable daily intake, there must be some proportion of
people who are getting more and some who are getting less. In other words, that
average does not really inform us adequately about the risks confronted by indi-
viduals in the population.
What we need to know is the frequency distribution curve. If that curve is
anything like the corresponding ones for other environmental agents, it will have
a log-normal form, tailing off to the high side. As a result, a significant propor-
tion of the population would be getting more than the acceptable daily intake. On
another point, I think that it is scientifically unacceptable to judge the environ-
mental impact of any material by dividing the amount disseminated in the entire
planet by the surface of the earth. For example, one slide showed that the
world average deposition of nitrogen fertilizer is 1.1 kilos per hectare, yet in
the state of Illinois, the rate of application is 100 times higher than that.
143
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Exposures to nitrate levels in surface waters derive from that actual deposition
rate and not from the world average.
DR. COULSTON: Sir, I didn't invent it. I told you where the slide came
from. It came from the International Atomic Energy Agency. Anyway, the slide
is ten to the sixth metric tons.
DR. COMMONER: Now let me comment on the question of carcinogenesis.
Take, for example, a problem that troubles many people, — that a carcinogen is
often active in one test species and not in another; that mice, for example, tend to
be more responsive to carcinogens than rats.
We now understand the reason for the differential response of test species
to carcinogens. The key observation is that what we call the carcinogen is almost
always not the active material. Rather, it is first metabolized, very often but not
necessarily in the liver, to yield the active material. For example, one of the
most potent carcinogens, AAF, is a very active carcinogen in the rat, but is in-
active in the guinea pig.
However, it was discovered that N-hydroxy AAF is produced in the liver
of AAF-fed rats and that is the active carcinogen. When this AAF metabolite was
injected into a guinea pig, tumors were produced. What does this mean about the
carcinogenic hazard to man?
We need to ask: To what degree do the bio-chemical properties of the
human liver resemble that of the guinea pig or the rat, and what variation in these
properties occurs among different individuals? There is now evidence that the
enzyme system that acts on carcinogens is genetically determined in man so that
there are genetic differences among people, which may very well explain the
differential response of people let's say to smoking.
144
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The reason why mice are so sensitive to carcinogens is that the strains of
laboratory mice have a much wider genetic variability than rats. Strains of mice
can be selected that are extraordinarily sensitive to carcinogens simply for the
reason that we have a wider spread of genetic variation in the available animals.
I only want to make one final comment. I've been very impressed in this
meeting with the opportunity for the people in the commercial field to come in
contact with the thinking not only of EPA personnel, but also of people in the aca-
demic world. It's clear that the decisions are going to have to be made in the
.commercial world.
I should like to suggest that the industry will be misled about the nature of
pesticide problems unless the points such as those I have just discussed are care-
fully considered.
DR. COULSTON: Dr. Commoner, let me just say this. I don't disagree
with anything you say. This has been going on for 20 years„ We who are in this
field of toxicology have considered everything you've said and we think we under-
stand toxicology. I'll say this then, I'm being very conciliatory, I don't think you
listened to all my points with an open mind, but that's all right. Arnold Lehman
(the grand old man of toxicology) used to say, you too can be a toxicologist in two
easy lessons, each ten years long.
145
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THE ROLE OF THE WORLD HEALTH ORGANIZATION
IN PESTICIDE RESEARCH
Frank C. Lu, M. D. *
WHO'S role in pesticide research falls into two distinct areas: One con-
cerns public health uses and the other, agricultural uses.
Some human diseases are transmitted by insects and other vectors.
Examples of important diseases of this type are malaria and schistosomiasis,
which affect millions of people in the world. One useful measure to control such
diseases is to reduce the relevant vectors by the use of pesticides. WHO, in
collaboration with research scientists in industry, governments, and universities,
has tested many potential pesticide chemicals. The relative values of these
chemicals are assessed with respect to their effectiveness against the vector,
their toxicities in laboratory animals, and their health hazards to the users and
the exposed population.
WHO'S activities in the other area need a bit more elaboration because they
are not directly concerned with research, but they contribute, nevertheless,
significantly in an indirect way.
First of all, I would like to point out that WHO'S objective is the attainment
by all peoples of the highest level of health. In order to achieve this objective,
WHO has a number of functions, one of which is the elaboration and promotion of
food standards. Because at an international level the supply of food is also a
matter within the competence of FAO, the two international agencies have estab-
lished a Joint Food Standards Programme. The principal organ of the Programme
is the Codex Alimentarius Commission. At present, the membership of the
Commission consists of 106 member states of WHO and/or FAO.
*Chief, Food Additives, World Health Organization
Preceding page blank 147
-------
The Commission is assisted by the Joint FAO and WHO Secretariat and
20 subsidiary bodies in carrying out its wide-ranging activities. The activities
are best shown by the organizational chart of the Commission (Figure 1). The
subsidiary bodies, also known as Codex Committees, fall into two main categories:
One deals with general subjects such as food additives, pesticide residues, food
hygiene, and methods of analysis and sampling; the other deals with groups of
specific food commodities. As the Commission has to deal with many subjects,
it has established criteria to determine the priorities. The criteria for general
subjects and commodity standards are listed in Figures 2 and 3 respectively.
In both cases the protection of the health of the consumer is the prime criterion.
A commodity standard contains the following provisions: scope, descrip-
tion, essential composition and quality factors, food additives, contaminants,
hygiene, weights and measures, labeling, and methods of analysis and sampling.
Limits for pesticide residues are not included in the commodity standards but
constitute separate standards.
The procedure for the elaboration of Codex standards is as follows: The
Commission decides that a standard should be elaborated and sets up a Codex
Committee or entrusts the elaboration to some other body. The Codex Committee
or other body produces a draft, which at this stage is a "proposed draft standard."
It is circulated to governments for comments and may be considered and further
amended by the appropriate coordinating committee in the case of a regional or
group of countries proposal. Otherwise, the "proposed draft standard" will be
considered or further amended by the Codex Committee or other body. It is then
presented to the Commission as a "proposed draft standard" and the Commission
uses it as the basis for producing a "draft standard." This is sent to governments
for comments, and in the light of these comments and after further consideration
by the Coordinating Committee or Codex Committee or other body, the
148
-------
Figure 1
RULE IX
l.tel
JOINT FAO/WHO COMMITTEE
OF GOVERNMENT EXPERTS
ON THE CODE OF
PRINCIPLES CONCERNING
MILK AND
MltK PRODUCTS
^WORLD-WIDE GENERAL]
I SUBJECT CODEX
[COMMITTEES j
ADVICE FROM
OTHER BODIES
FAO/WHO EXPERT
COMMITTEE ON
FOOD ADDITIVES
FAO/WHO JOINT
MEETING ON PESTICIDE
RESIDUES
FAO/WHO CODEX
ALIMENTARIUS
COMMISSION
1^ SUBSIDIARY BODIES 1
OF THE |
1 COMMISSION .
I L 1
I RULE IX I
I I.(W.I. |
I -,
WORLD-WIDE
COMMODITY CODEX
COMMITTEES
^ FAO/WHO
SECRETARIAT
EXECUTIVE
COMMITTEE
COCOA PRODUCTS
AND CHOCOLATE
(Switzerland)
SUGARS
(United Kingdom)
PROCESSED FRUIT
AND VEGETABLES
(U.S.A.)
FATS AND OILS
(United Kingdom)
EDIBLE ICES
(Sweden)
DIETARY FOODS
(Fed. Rep. Germany)
FISH AND FISHERY
PRODUCTS
(Norway)
MEAT
(Fed. Rep. Germany)
MEAT HYGIENE
(New Zealand)
PROCESSED MEAT
PRODUCTS
(Denmark)
RULE IX I
l.lbl.J. I
! REGIONAL
CO-ORDINAIINC
COMMITTEES
EUROPE
AFRICA
U.N.E.C.E. COD€X I
AUMENTARIUS GROUPS]
LOF EXPERTS j
FRUIT
JUICES
QUICK FROZEN
FOODS
JOINT FAO/WHO FOOD STANDARDS PROGRAMME
-------
Figure 2
Criteria Applicable to General Subjects
Consumer protection from the point of view of health and fradulent practices.
Diversification of national legislations and apparent resultant impediments to
international trade.
Scope of work and establishment of priorities between the various sections of
the work.
Work already undertaken by other international organizations in this field.
Type of subsidiary body envisaged to undertake the work.
Figure 3
Criteria Applicable to Commodities
Consumer protection from the point of view of health and fradulent practices.
Volume of production and consumption in individual countries and volume and
pattern of trade between countries.
Diversification of national legislations and apparent resultant impediments to
international trade.
Amenability of the commodity to standardization.
Number of commodities which would need separate standards indicating whether
raw, semi-processed, or processed.
Work already undertaken by other international organizations in this field.
The type of subsidiary body envisaged to undertake the work.
150
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Commission reconsiders the draft and adopts it as a "recommended standard."
This is sent to governments for acceptance and is published in the Codex
Alimentarius as a Codex standard, when the Commission determines that it is
appropriate to do so in the light of the acceptances received.
Following this elaborate procedure the Commission, with the assistance of
its subsidiary bodies, has already adopted a number of Codex standards (Figure 4)
that have been translated, printed, and transmitted to the governments of member
states for their consideration for acceptance. In addition, the Commission has
elaborated a number of methods of analysis and codes of practice. These are
listed respectively in Figures 5 and 6. Additional standards, methods, and codes
have been adopted by the Commission, but these are being translated and/or
printed before submission to the governments.
Figure 4
List of Recommended CODEX Standards Issued To-Date to Governments
for Acceptance, February 1974
Labeling
CAC/RS 1-1969 -General Standard for the Labeling of Pre-packaged
Foods
Pesticide Residues
CAC/RS 2-1969 -Tolerances for P. R. - 1st Series
CAC/RS 35-1970 -Tolerances for P. R. - 2nd Series
CAC/RS 43-1971 -Tolerances for P. R, - 3rd Series
Fish
CAC/RS 3-1969 -Canned Pacific Salmon
CAC/RS 36-1970 -Quick Frozen Gutted Pacific Salmon
CAC/RS 37-1970 -Canned Shrimps or Prawns
CAC/RS 50-1971 -Quick Frozen Fillets of Cod & Haddock
CAC/RS 51-1971 -Quick Frozen Fillets of Ocean Perch
151
-------
Figure 4 (continued)
Sugars
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
Processed
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
4-1969
5-1969
6-1969
7-1969
8-1969
9-1969
10-1969
11-1969
12-1969
54-1971
-Wl
-Po
-So
-De
-De
-Gl
-Di
-La
-Ho
-Po
Fruits and Vegetables
13-1969
14-1969
15-1969
16-1969
17-1969
18-1969
42-1970
-Ca
-Ca
-Ca
-Ca
-Ca
-Ca
-Ca
Edible Fats and Oils
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
19-1969
20-1969
21-1969
22-1969
23-1969
24-1969
25-1969
26-1969
27-1969
28-1969
29-1969
30-1969
31-1969
32-1969
33-1970
34-1970
-Ge
T_J
ino
-Ed
-Ed
-Ed
-Ed
-Ed
-Ed
-Ed
-Ed:
-La
-Re:
-Pr
-Ed
-Ma
-Oil
-Mu
-Powdered Sugar (Icing Sugar)
-Soft Sugars
-Dextrose Anhydrous
-Dextrose Monohydrate
-Glucose Syrup
-Dried Glucose Syrup
-Lactose
-Honey (European Regional Standard)
-Powdered Dextrose (Icing Dextrose)
-Canned Tomatoes
-Canned Peaches
-Canned Grapefruit
-Canned Green Beans & Wax Beans
-Canned Applesauce
-Canned Sweet Corn
-Canned Pineapple
General Standard for Fats & Oils not Covered by
Individual Standards
Edible Soya Bean Oil
Edible Arachis Oil
Edible Cottonseed Oil
Edible Sunflower Seed Oil
Edible Rape Seed Oil
Edible Maize Oil
Edible Sesame Seed Oil
Edible Safflower Seed Oil
Lard
Rendered Pork Fat
Premier Jus
Edible Tallow
Margarine
Olive Oils
Mustard Seed Oil
152
-------
Figure 4 (continued)
Edible Fungi
CAC/RS
CAC/RS
CAC/RS
38-1970 -General Standard for Fungi and Fungus Products
39-1970 -Edible Dried Fungi
40-1970 -Fresh Fungus "Chanterelle" (European Regional
Standard)
Quick Frozen Fruits and Vegetables
CAC/RS
CAC/RS
41-1970
52-1971
-(
-(
Fruit Juices
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
CAC/RS
Foods for
44-1971
45-1971
46-1971
47-1971
48-1971
49-1971
63-1972
64-1972
Special Dietary
-i
-(
-(
-]
-i
r
-(
-<
Uses
CAC/RS 53-1971
-Quick Frozen Peas
-Quick Frozen Strawberries
-Apricot, Peach and Pear Nectars
-Orange Juice
-Grapefruit Juice
-Lemon Juice
-Apple Juice
-Tomato Juice
-Concentrated Apple Juice
-Contrated Orange Juice
-Foods with Low Sodium Content (Including Salt
Substitutes)
153
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Figure 5
List of Recommended International Codes of Practice, February 1974
CAC/RCP 1-1969 -General Principles of Food Hygiene
CAC/RCP 2-1969 -Canned Fruit and Vegetable Products
CAC/RCP 3-1969 -Dried Fruits
CAC/RCP 4/5-1971 -Dessicated Coconut and Dehydrated Fruits and
Vegetables Including Edible Fungi
CAC/RCP 6-1972 -Tree Nuts
Figure 6
List of Related Recommended Texts Sent to Governments, February 1974
CAC/RM
CAC/RM
CAC/RM
CAC/RM
CAC/RM
CAC/RM
1/8-1969
9/14-1969
36-39-1970
32-1970
33-1970
42-1969
-Methods of Analysis for Sugars
-Methods of Analysis for Fats and Oils
-Methods of Analysis for Processed Fruits and
Vegetables
-Standard Procedure for Thawing of Quick Frozen
Fruits and Vegetables
-Standard Procedure for Cooking of Quick Frozen
Vegetables
-Sampling Plans for Prepackaged Foods (AQL 6.5)
154
-------
WHO and FAO have been convening joint meetings on pesticide residues since
1961. The current series of Annual Joint Meetings of the FAO Working Party and
the WHO Expert Committee on Pesticide Residues began in 1966. The agenda of
the Joint Meeting is usually drawn up on the basis of the recommendations of
the Codex Committee on Pesticide Residues, which is attended not only by dele-
gates of governments but also by representatives of industrial concerns and of
international organizations. Once the list is drawn up, it is sent to the manu-
facturers of pesticides to solicit published and unpublished data. Attempts are
also made to search the open literature. The information so collected is
reviewed and summarized by temporary advisers to WHO; their working
papers are sent to the manufacturers who submitted the data. The manufacturers
are, in general, extremely cooperative in reviewing the working papers and in
making comments which are given full consideration by the Expert Committee at
its meeting. On the basis of the original data and the temporary advisers'
papers, a second set of working papers is prepared by the members of the
Expert Committee. All these papers are circulated to the members before the
meeting. *'
At the meeting, a set of monographs is prepared. Each monograph contains
summaries of the relevant data, comments on the data, a toxicological evaluation,
and a list of further information required or considered desirable. The toxicolog-
ical evaluation of a pesticide for which adequate information is available will lead
to the establishment of an acceptable daily intake for man. This figure is
expressed in terms of milligrams of the chemical per kilogram of body-weight. In
cases in which the information is not fully adequate, a temporary acceptable
daily intake is established for a period of 3 to 5 years, and the further informa-
tion that is required is stated. In certain cases, the further information is
considered desirable although not essential in the establishment of an acceptable
daily intake.
155
-------
The task of the FAO Working Party is to review the "residue data." This
includes the use pattern, the residue resulting from supervised trials, the fate of resi-
dues, the methods of residue analysis, and the national tolerances. On the basis
of these data, the Working Party recommends limits for residues of pesticides
in specific food commodities. The residue data as well as the recommended
tolerances are also included in the monographs.
In addition to the monographs, the Joint Meeting also prepares a report
during the meeting. The report contains the main decisions and recommendations
as well as matters of a general nature. There are, in addition, two annexes: One
lists the acceptable daily intakes and the residue limits proposed, and the other
lists the further work required or desired. Sometimes other annexes such as a
glossary are included to provide additional information concerning specific
subjects.
The relationship between the various organizations concerned with the
evaluation and control of pesticide residues and the impact on pesticide research
are shown in Figure 7. The toxicological and related data, as well as the residue
data are provided by research scientists to the national authorities, such as the
Environmental Protection Agency. At an international level these data are
collected by WHO and FAO for use by the Joint FAO/WHO Meeting on Pesticide .
Residues. The recommended acceptable daily intakes and the tolerances from the
Joint Meetings are transmitted to the Codex Committee on Pesticide Residues,
which elaborates draft Codex tolerances. After the views of member states and
other international organizations have been received, these are reviewed by the
Codex Alimentarius Commission. Following the procedure as described above,
156
-------
Figure 7
en
-q
c
/^To>
V^dat
*.
c-colog-caT^,
|
Research Scientists
in
Academia, Government, Industry
H^ NATIONAL AUTHORITIES \+
WORLD HEALTH
ORGANIZATION
(WHO)
Request for \^
information J*
\
^ Residue data J
1
FOOD 6 AGRICULTURE
ORGANIZATION
(FAO)
Joint Meetings
WHO ! FAO
Expert ' Working
Committee i Party
•
-C
— -•
/Acceptable dalivN
^Intakes ^^/l
Tolerances, etc.
CODEX COMMITTEE ON PESTICIDE RESIDUES
/'Draft CodexN
V^tolerances ./
CODEX ALIMENTARIUS COMMISSION
X^Reoommended'
(^Codex tolerances
ded'N
ances^
GOVERNMENTS
Enforcement
Cprotection^N
of health }
CONSUMER
RELATIONSHIP BETWEEN THE VARIOUS ORGANIZATIONS CONCERNED
WITH THE EVALUATION AND CONTROL OF PESTICIDE RESIDUES
-------
the Codex Alimentarius Commission eventually adopts these tolerances as
recommended Codex tolerances. These are then sent by the Directors-General
of WHO and FAO to the governments of member states for their consideration
for acceptance. Once a government has accepted the Codex tolerance it is men
obligated to enforce the tolerance. The enforcement will ensure the protection
of the health of the consumer, allow the proper use of pesticides in agriculture,
and facilitate trade of food.
In reviewing the toxicological and the residue data, the Joint Meeting may,
on the other hand, consider that the information available is inadequate. In such
cases the further information required will be transmitted to the research
scientists in the industry, government, and universities to promote the develop-
ment of relevant information.
Dr. FREDERICK WfflTTEMORE: I should like to make just one comment
with respect to Dr. Lu's description of the work of the Expert Committees and its
relationship to the Codex Committee. And that is that at the time the monographs
and the reports are prepared by this Joint Meeting, they are sent to all member
governments of the two organizations. They are also sent into the Codex procedure,
and there was one rather critical figure that he gave there of 103 member govern-
ments of the Codex Commission. However, it's my understanding that within the
Codex Commission, the member governments which are participating actively in
the work of the Committee on Pesticide Residues are a much smaller number,
possibly on the order of 45 or 50. This has a rather grave implication with respect
to the worlwide scope of these recommendations because many of the governments
which are not participating actively in the work of the Codex Committee on Pesti-
cide Residues receive these recommendations from the Joint Meeting and in many
158
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instances incorporate these recommendations into their national legislation. This
will lead to a false sense of security, so to speak, unless these other recommenda-
tions are properly handled through the Codex Committee on Pesticide Residues.
There are many countries which are affected by this procedure other than those
who are actively participating in the Codex procedure.
DR. F. C. LU: Dr. Whittemore is absolutely correct in his statement that
the Codex does not cover all the member states and not all the countries in the
world. I did not emphasize this particular point for the simple reasons that first,
we're short of time and secondly, I am hopeful that there will be more governments
participating more actively in the Codex program.
I remember at the beginning of the Codex program there were only 39
countries and those were practically all in Europe. Now this has been extended
throughout the whole world, including all the continents, so that I think the direct
influence of the work of the Joint Meeting on the member states will gradually
diminish and the importance of the Codex Program will increase. I hope
Dr. Whittemore would agree with that.
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THE ROLE OF THE FOOD AND AGRICULTURE ORGANIZATION
IN PESTICIDE RESEARCH
Edgar E. Turtle, Ph. D. *
I had reservations in accepting the invitation to speak on this subject. This
is because the primary task of FAO is to help member countries, and particularly
developing countries, in the production of food and other agricultural commodities,
whereas the conduct of scientific research is not specifically charged to the organ-
ization.
Emphasis On Field Development Activities
Pursuant to these objectives much of the assistance given by the Organi-
zation in the control of pests of agriculture during recent years has been through
field development projects. These have been funded by the U. N. Development
Programme and other bodies and technically supervised by internationally re-
cruited specialists who operate under the general guidance of Headquarters Divi-
sions in Rome. A large part of the activity within these field development projects
should be regarded purely as extension or advisory work. The extent to which
they are engaged in research varies widely according to the native and immediate
objectives of the project.
As examples, there are projects designed to give guidance on the official
registration and control of pesticides which include no experimental work; there
I
are projects which fall under the Integrated Pest Control Programme which aim
to work up methods for controlling specific pests and to demonstrate the pro-
cedures of integrating chemical with biological approaches to the control of pests;
there also are projects, such as that for finding acceptable alternative insecticides
for the control of locusts in which the activity is entirely research in content.
"Pesticide Specialist, Food and Agriculture Organization
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This is an area of interest that warrants further study and possibly cooperative
action on a national or international basis. Unfortunately we in FAO can only use
persuasion to engender work on such items since, until now, we have not been
successful in approaches to funding bodies to sponsor research work on such items.
Hopefully, the new initiatives covered by the Resolution passed at the Bellaglo
Conference will cover this problem.
Pesticides in The Integrated Pest Control Programme
Although It would be misleading to list the Integrated Pest Control Pro-
gramme specifically as part of the "FAO Pesticides Programme," which relates
to the programme as set up after the 1962 Conference, it would be equally mis-
leading to omit mention of the programme in any outline of FAO's interests in
research with pesticides. Thu programme was launched at a symposium held
in Rome in October 1965. It is supported by a panel of experts formed in 1966,
which reviews principles and elaborates procedures for promoting interdisci-
plinary programmes for the integrated control of major pests based on ecological
considerations. Particular attention has been paid to developing procedures on
crops such as cotton, on which excessive quantities of pesticides have often been
used. In these developments, pesticides are regarded as components In pest
management systems, rather than eradicants of pests as in the older conception.
This opens up new perspectives and criteria in assessing the value of new pesti-
cides which, of course, include studies of the advantages and problems involved
in the introduction of narrow-spectrum compounds.
For further development of these themes, reference should be made to the
various reports of meetings of the expert panel and also to the recently issued report
of the Conference on Ecology in Relation to Plant Pest Control held in Rome in
December 1972.
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The few chemists employed In these field projects are engaged almost
entirely in advising on procedures, Including laboratory methods for detecting
and measuring residues; that is, in helping to provide background technical know-
how, rather than in implementing research programmes.
Technical and Research Contents of the Pesticides Programme
These references to field support activities have been located at the open-
ing of this statement to draw attention to their importance in relation to the primary
aims and objectives of the Organization. They must be fully taken into account in
the formation of lines of policy by the relevant technical divisions.
In their broad principles these lines of technical policy must meet the
wishes of the member countries. In the case of pesticides this was first expressed
in an intergovernmental conference in 1962. Details of the programme result
substantially from consultations with specialists, individually or in meetings
arranged for this purpose. These meetings may be of formally established work-
ing parties, panels, or committees, or they may be organized on an ad hoc basis.
As for the field projects, the involvement of the expert groups directly in
matters of research varies widely from one to another. No group is constituted
or funded specifically to undertake or to sponsor research. The following comments
indicate the manner in which various ongoing activities engender or stimulate re-
search in the pesticides field.
Of the three Working Parties of Experts set up with the launching of the
pesticides programme in 1964, that group on Official Control of Pesticides is
charged with providing guidance on registration and other procedures of official
control. It has issued general guidelines and is now mainly engaged in issuing
standard specifications. This latter activity involves the evaluation of evidence
more than the initiation of new research.
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The Working Party on Pest Resistance to Pesticides has undertaken a
general survey of the occurrence of resistance among agricultural pests. Quite
recently it has sponsored a worldwide special survey of resistance to pesticides
among post-harvest pests of cereals. It has also provided technical support for
a series of publications of standard methods for investigating for the occurrence
of resistance in field populations. Currently a new manual on the subject is being
prepared by a specially appointed consultant.
The Working Party on Residues of Pesticides has met jointly with the WHO
Committee of Experts annually since 1965. It has evaluated data relating to the
occurrence and toxicology of residues of some 130 pesticides and made recommen-
dations for acceptable levels in foods for many of them. The recommendations
from these Annual Joint Meetings provide the basis for intergovernmental dis-
cussions with the Codex Alimentarius Commission.
When the information reviewed by the experts is considered to be insuf-
ficient for any scientific or other reason, recommendations are withheld or, with
minor deficiencies, are proposed only on a temporary basis. In these instances
o
the nature of the deficiency and the kind of research required Is recorded In the
published report accompanied by the period after which It Is Intended to review
the position. These periods are set so as to provide a reasonable time for under-
taking the necessary research and in the hope that new data will have become
available for the subsequent reevaluatlon. In many Instances — and this par-
ticularly applies to those in which companies have a continuing patent coverage —
additional data have become available and it has been possible to make new rec-
ommendations or to remove the "temporary" qualification. In some instances
however — and this applies particularly to some of the older common pesticides —
new data to meet current criteria have not become available.
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These activities have recently obtained encouragement from the U. N.
Environment Fund, which is currently supporting a project of preliminary studies
which, hopefully, should lead to the wider adoption of these principles in the
control of pests in developing countries.
Environmental Impacts of Increasing Use in Developing Countries
It seems certain that increasing quantities of pesticides will undoubtedly
be used in developing countries for some years to come. This is partly due to
the rapidly increasing demands for food production in the developing countries
and partly due to the fact that the introduction of new techniques of pest control
and, indeed, of new pesticides is inevitably a fairly slow process. This means
that there will be a continuing need to provide support for safe practices in use
and for the study of and avoidance of environmental problems where possible.
For some years, we have had ongoing programmes related to the occurr-
ence of residues of pesticides in food. This takes the form of the Annual Joint
Meetings of the Working Party on Residues on Food, and support has been given
in various projects designed to help developing countries to measure and control
residues in their foods. Until recently we have had no funds and no panel of
experts specifically concerned with the occurrence of residues and with their
effects elsewhere in the environment. Recently, however, the U. N. Environment
Fund has accepted our proposal for initiating a coordinated programme aimed in
the first instance at investigating possible environmental problems arising from
known uses of pesticides in developing countries. We are planning to launch this
programme at a meeting to be called in Rome early in 1975.
Future Plans and New Initiatives
What of the future! First, it must be recorded that within the limits of
our resources we hope to continue with the above mentioned activities. They
adhere to the general objectives set by governments 12 years ago at the 1962
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Pesticides Conference. This was to promote safe practices and to raise technical
levels of application as a means of taking maximum economic and social advantages
while studying problems and taking avoiding actions whenever the need is shown.
At the same time, in the light of the problems still, if not increasingly,
being encountered In the control of both agricultural and public health pests, we
feel that new comprehensive and coordinated efforts are needed to ensure that the
necessary resources are mobilized and used effectively to Implement new initi-
atives for solving pest problems on an international basis. We feel that there is
an increasing array of knowledge, In the form of knowledge of ecological require-
ments for controlling given pests and a variety of new materials. But increased
research and practical development resources will be needed if the problems are
to be overcome within a reasonable period.
These views were discussed at a Rockefeller Foundation sponsored con-
ference in Bellaglo, Italy In April 1974, when proposals were drafted for Inter-
national coordination of developments In the plant protection area with special
emphasis on pesticides and alternative chemical programmes.
The proposal Included the suggestion that there should be a secretariat
housed with FAO and with units In WHO. It was formally passed to the Director-
General of FAO and In July of this year was approved In principle by the FAO
Council (I.e., the Governing Body), subject to the need for further elaboration.
It Is envisaged that this will be done during the coming year. As the proposal,
which has been tentatively described as an "International Programme for Control
of Pests Affecting Agriculture and Human Health," Is open for general examination,
It Is timely for me to draw your attention to it at this symposium.
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The objectives as stated in the original proposal are: *
1. To provide a method of mobilizing in a coordinated way the best world-.
wide talent in the various specialities related to control of pests of agriculture and
human health with focus on developing the soundest programmes and jointly initiat-
ing the required actions to solve these increasingly pressing problems.
2. To mobilize the required financial and human resources required for
the level of sustained effort required to accomplish these objectives.
3. Provide a means of influencing to the maximum extent possible the
policies and attitudes of governments, industries, and the general public to ensure
the necessary support and understanding required to obtain the proper implemen-
tation of the programmes of pest control deemed desirable.
4. Provide a mechanism for developing the body of knowledge and infor-
mation required to enable the introduction of chemicals and control procedures
into the human environment with an adequate insurance of environmental safety
without unnecessary delay and expense.
5. To develop an effective international research network to obtain the
necessary information and act as a source of data on the nature of pest problems
in the different ecosystems important to man, and evaluate and develop the param-
eters required for effective control systems.
6. Provide the means for discovery and development to the use stage of
new chemicals and devices which fit the requirements of control operations either
directly through this programme or in cooperation with the world industries,
*Taken from the program proposal adopted by resolution at the Bellagio Conference,
April 1974.
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and provide the means for licensing or assisting industries on a mutually
advantageous basis to introduce products useful in pest control which would
not normally be developed by unassisted commercial endeavor.
7. Stimulate research on products and devices now in common use to
determine how they can be used more efficiently and safely in pest control pro-
grammes.
8. Provide the basis for a training network which can provide the number
and quality of people trained adequately to provide the required manpower for the
various components of pest control programmes from research to operational
aspects.
9. Provide a source for obtaining consultation and suitable personnel for
technical assistance programmes being provided for governments and to provide
assistance to industries for obtaining the information required to make sound
decisions.
10. Provide mechanisms to ensure maximum rapid exchange of information
and personal discussion among and within the various groups dealing with or
dependent upon pest control.
The organizational structure is also referred to in the following manner:
The programme Is designed to provide an international secre-
tariat operating under the authority of a governing board to develop
with the assistance of a series of advisory committees compre-
hensive and coordinated programmes to be carried out through
research contracts and agreements or other procedures to imple-
ment coordinated programmes in the fields of pesticide toxicology,
"pesticide chemistry, physiology and biochemistry, environmental
impact, international registration standards, and appropriate bio-
logical groups designed to develop the requirements for the type of
basic pest control programmes required.
In each of these areas programmes may include research, train-
ing, technical assistance and advisory or consulting services.
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Developing methods to expedite the rapid exchange of information
should be included in the responsibility of the programme.
The secretariat would be comprised of an executive secretary
and coordinators for each of the programme areas. The programme
budgets and activities including the secretariat would be the re-
sponsibility of a governing board. The programmes and budget
proposals for each of the areas would be developed by advisory
committees working with the area coordinator. A key element
in the programme development and evolution in each area would
be an annual meeting of participants in each area to present their
findings to the advisory committee and assist the advisory com-
mitte in development of programmes and budgets.
In addition to these various programme areas, there would also
need to be facilities to handle patents, contracts and licenses.*
From the above Indication of the present discusslonal status of these pro-
posals, it Is obviously not possible to give you any firm assurances regarding the
future programme of our Organization in this field other than a continuation of
that covered by the earlier part of this paper.
Finally on behalf of FAO, I must express our grateful thanks to the En-
vironmental Protection Agency for the Invitation to this symposium, both for the
purpose of hearing of the plans of the Agency and of being able to present this
paper on our programme. Although the implementation of our intentions must be
contingent on our obtaining the necessary funding resources, I can assure you as
a staff member of the Plant Protection Service of the Plant Production and Pro-
tection Division, that we do propose to press our efforts along the lines indicated.
"Program proposal adopted by resolution at the Bellaglo Conference, April 1974.
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U. S. PARTICIPATION IN CODEX
Lowell E. Miller*
The Codex Alimentarius Commission came into being in 1962, 12 years
ago. In 1963 the Commission, at its first session, established the Codex
Committee on Pesticide Residues (CCPR) with the responsibility to propose
international tolerances for pesticide residues in specific foods. Since that time,
the CCPR has met in seven sessions, the last in February 1974.
There are now about 1,000 proposed tolerances at some stage in the Codex
process. Approximately 100 of these have been formally submitted to member
countries for acceptance. Another 140 proposed tolerances will soon be
recommended to member countries for acceptance as a result of the actions
taken at the July 1974 meeting of the Commission. Obviously, the wheels of
Codex have been grinding.
Yet today in 1974 blunt questions are being asked about the future of Codex.
Questions such as: Will Codex "get off the ground"? Will Codex live up to its
high promises? These questions are prompted, I think, by the fact that while a
great many tolerance proposals are in the Codex process, the Codex pesticide
residue work has yet to produce observable results; Codex has not yet demon-
strated that countries will agree to or accept a significant number of pesticide
residue tolerances.
It goes without saying that the United States has a great concern for the
future of Codex (and when I refer to "Codex," I want to make clear that I am
referring to the work of Codex as it relates to the establishment of international
tolerances for pesticide residues in foods). The United States has always strongly
supported the principles of the Codex Alimentarius Commission. We have also
*Asststant for Legal and Regulatory Affairs, Office of Pesticide Programs,
U. S. Environmental Protection Agency
171
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voiced strong support for the work of the CCPR. But we have never really come
to grips with certain key questions which must be answered before we can fully
participate in the Codex work.
And we in the United States are not alone in this situation. I find that the
questions we have been trying to resolve are the same questions being grappled
with in other countries.
I do not intend this morning, however, to talk about the participation of
other countries in Codex. Rather, I would like to discuss U. S. participation In
Codex — specifically, to Identify the questions and to discuss what we have done
to answer these questions and where we go from here.
First of all, a few background remarks about Codex:
The Codex Alimentarius Commission is an international body concerned
with the development of international food standards, including maximum limits
for pesticide residues in food. The Commission was established to implement
the Joint Food Standards Program of the Food and Agriculture Organization of
the United Nations (FAO) and the World Health Organization (WHO). Membership
in Codex is made up of those members of FAO and WHO who have notified the
organizations of their desire to be members of Codex. At present, approximately
100 countries are members of Codex.
The purposes of the Commission, broadly stated, are to protect the health
of consumers and to ensure fair practices in the food trade.
The work of the Commission is carried out through various committees,
each chaired by one of the participating countries. A number of Codex Committees
have been established to elaborate standards for various major food commodity
groups (e.g., milk and milk products, fats and oils, sugars, meats, fish and
fishery products). Other committees deal with particular problems associated
with the commodity groups (e.g., food additivies, food labeling, food hygiene,
methods of analysis and sampling, pesticide residues).
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Maximum residue limits for pesticides (tolerances) are developed through
a 10-step procedure. This procedure gives member countries an opportunity
to review and comment on tolerance proposals at various stages of the process.
In essence, there are three distinct phases of the Codex work.
FAQ/WHO Joint Meeting
The principal scientific work Is carried out by experts appointed by
the Directors-General of FAO and WHO and Is supported by a permanent
secretariat. The experts come together In an annual meeting (Joint Meeting) to
discuss the results of their evaluations of assigned compounds and to prepare
appropriate recommendations. Chemicals are reviewed by the Joint Meeting on
the basis of priorities recommended by the Codex Committee on Pesticide
Residues. Toxicological ard residue data and information on appropriate methods
of analysis may be submitted to the Joint Meeting from any country. The Joint
Meeting, upon the basis of the information available, proposes tolerances,
temporary tolerances, or practical residue limits for the pesticide. A mono-
graph on each chemical is prepared by a member of the Joint Meeting. In
addition, reports of the Joint Meetings are published. These reports, together
with an abbreviated version of the monographs, set forth the bases for the Joint
M eeting p ropos als.
The Codex Committee on Pesticide Residues (CCPR)
The CCPR provides the forum for discussions among countries on the
proposed tolerances. Countries are invited to submit written comments on the
proposals at steps 3 and 6 of the Codex procedure. The detailed consideration
of tolerance proposals and written comments, however, occurs at the CCPR
sessions. At CCPR sessions, countries are expected to indicate concurrence or
nonconcurrence on each tolerance proposal. It was made clear at the last
session of the CCPR (February 1974) that in cases in which a country did not
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concur with a proposal, that country was expected to give a specific reason
for the nonconcurrence. It was also made clear that a different national
tolerance, in Itself, was not considered a sufficient reason for nonconcurrence.
Countries are expected to give the basis for any objection supported by data.
Commission Recommendations for Acceptance
The end result of CCPR work Is the forwarding of tolerance proposals
to the Commission with recommendations that the proposals be submitted to
member countries for acceptance as international tolerances. When the
Commission concurs with CCPR actions (step 8), the proposals are formally
submitted to member countries with the request that the Commission be notified
of their acceptance in accordance with the General Principles of the Commission
(step 9).
It is at this point that we come to the core question in the establishment of
international tolerances: What is meant by "acceptance" of a Codex proposed
tolerance? Asked another way, what commitment does a country make when it
"accepts" a Codex proposal?
But these are questions which are not only relevant to the end step of the
Codex process when proposals are formally submitted to countries for
acceptance; these are questions, it seems to me, which must be resolved before
a country is in a position to give full consideration to a tolerance proposal at
the earliest step in the Codex review process (step 3). How can a country
determine what its position is with respect to a proposed international tolerance
at any step until it has also determined what "acceptance" of such tolerance
means ?
The Codex General Principles define "acceptance" and set form the pro-
cedures for the acceptance of Codex proposals. At the last meeting of the Codex
Alimentsrius Commission, held in July 1974, a new and separate acceptance
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procedure was established for pesticide residues. Under these procedures, there
arc three types of acceptances.
1. "Full acceptance" which means that a country agrees to apply the Codex
tolerance to both imported and domestic food.
2. "Limited acceptance" which allows a country to apply a Codex tolerance
t .
to imports only. Under "limited acceptance," however, a country may not apply
a more stringent (lower) tolerance on imports. This is a new type of acceptance
and is intended to make it easier for countries to recognize good agricultural
practice in another country. It also makes it clear that a country may (a) recog-
nize a higher tolerance for imported food than for domestic food and (b) accept
a pesticide residue tolerance on imported commodities while, at the same time, .
it restricts or prohibits tho use of the pesticide in its own country. ,f
3. "Target acceptance" which allows a country to indicate its intention to •' •
give full acceptance or limited acceptance to a Codex tolerance after a stated
number of years.
In the United States, there are three agencies which are vitally concerned ••"•'•'
with the Codex acceptance procedures — FDA, USDA, and EPA. EPA would seein :
most heavily involved since EPA has the responsibility to establish pesticide - * •'->'
tolerances under our national statutes. FDA and USDA enforce these tolerances.
USDA is also concerned because of its responsibilities for foreign trade in
agricultural commodities. • '•'..»*
•'; .. %
In recent months, representatives of these three agencies have had dis-
cussions concerning the U. S. position on acceptance of a Codex tolerance. Two
basic tenets have emerged from these discussions:
1. Before a Codex proposed tolerance may be accepted, it must be deter-
mined that the Codex tolerance fully complies with the requirements of our
: t \
national law and a regulation establishing such a tolerance must have been
promulgated. In short, the establishment of a tolerance under national law is
a condition precedent to our accepting a Codex tolerance.
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2. At present, we will not operate on a so-called two-tolerance concept;
that is, we will not establish differing tolerances for imported and domestic
foods. However, we do not want to foreclose the possibility of considering the
establishment of a different tolerance for an imported commodity in a specific
situation if circumstances warrant.
The application of these tenets to our Codex tolerance review work seems
clear.
We in EPA will review each proposed Codex tolerance to determine
whether it complies with the requirements of U. S. law, giving full recognition
to the U. S. position, as stated at the last meeting of the Commission, that the
United States will strive to give "full acceptance" to as many as possible of the
proposed tolerances recommended by the Commission for acceptance.
When the Codex recommended tolerances differ from established U. S.
tolerances, we will review each proposal from the standpoint of determining
whether changes can be made In the U. S. tolerance level. In all possible cases,
action will be initiated under U. S. statutes to make the U. S. tolerances consis-
tent with the Codex proposals. When the United States cannot accept a Codex
proposal for reasons of good agricultural practice In this country or for human
health reasons, the reasons for our nonacceptance and the data upon which our
decision Is based will be fully set forth.
We also support the principle that would allow a country accepting a Codex
tolerance to apply such tolerance to Imports only, while prohibiting or restricting
the use of the pesticide domestically. We will follow this principle. It is important
to recognize that the establishment of a tolerance for a pesticide chemical and
the registration of the pesticide for use are two related but separate actions.
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Codex proposed tolerances fall into four categories as they relate to U. S.
tolerances:
1. The Codex proposed tolerance is the same as an established U. S.
tolerance. Here, of course, there is no problem and we can accept the Codex
proposal without further review. The United States has formally accepted those
Codex tolerances now at step 9 that correspond to U. S. tolerances.
2. The Codex proposed tolerance is lower than the U. S. tolerance. Here
the question is one of analysis of all available residue data to determine whether
the U. S. tolerance can be lowered in accordance with good agricultural practice
in the United States.
3. The Codex proposed tolerance is higher than the U. S. tolerance. Here
the question is one of safety. In my opinion, the United States must be willing to
raise U. S. tolerances to a higher Codex level if such can be supported scientifically.
The United States cannot accept only those Codex tolerances which are equal to or
less than a U. S. tolerance. If we expect other countries to recognize good agri-
cultural practices in the United States, we must do the same in the absence of a
determination that the higher tolerance cannot be justified for human health reasons.
4. The proposed Codex tolerance is for the residue of a pesticide not
registered for use In the United States. Here as indicated before we can and, as a
matter of fact, have established tolerances even though the pesticide Is not regis-
tered for the use in question in the United States.
Finally I would like to make some personal observations:
While Codex has been criticized for its cumbersome procedures and for its
lack of visible accomplishments, I believe that significant work has been done in
the CCPR in the last few years. The problems have been identified and discussed;
differing views have been aired; a real effort has been and is being made to make
the work of Codex more effective. I believe that we will see real progress in
the work of Codex in the years immediately ahead.
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I am, therefore, optimistic about the future of Codex. I say this for two
reasons in addition to what I have Just said. First, I believe there is a realization
in all countries mat we are, in the words of one CCPR delegate, at "pay day."
Countries can no longer dodge the question of formal acceptance of an international
tolerance; we are being forced into demonstrating what our commitments to the
principles of Codex are. Second, I came away from the last session of the CCPR
with the distinct feeling that it was the mood of the session that Codex must work
and that it can. This feeling was in large part due to the firm and able leadership
of our Chairman, Dr. Pieters of the Netherlands. It was also due to the
expressions of many of the delegates with whom I talked, that the objectives of
Codex can best be achieved on a global rather than regional basis and that national
policies with respect to the regulation of pesticides should not present irreconcil-
able differences with the objectives of Codex.
QUESTION: Is there not a basic difference in what Codex calls a tolerance
and how we establish our tolerances In terms of the residue base data? That is,
we are required to establish tolerance based on the highest residue levels that we
find In a prescribed try. Now I get the impression — I can't remember what they
call It in Codex, you probably will — that that's not necessarily the case for Inter-
national tolerance. Is the number that Is quoted necessarily representative of
the absolute maximum when used as directed ?
MR. LOWELL MILLER: We could have a long discussion about the differ-
ing philosophies In the so-called high-tolerance and low-tolerance countries. Part
of the difference arises because of our law. Our tolerance procedures are man-
dated by statute. Under our law, any food that exceeds the tolerance level Is
adulterated. In my opinion, we cannot establish a tolerance on a mean batch
concentration and excuse violations that are over that mean. But this Is a philo-
sophical question which I don't think we have time to get Into right now. We can
discuss It later.
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QUESTION: Mr. Miller, I recall a comment from you and also Dr. Lu
with regard to accepting tolerances based on domestic production as well as
import, but neither of you commented on considering these same tolerances with
regard to exported foods and it seems to me this is a very important picture.
In exporting from here to Europe there may be no problem, but in many
cases we are exporting to the lesser developed countries where frequently they
have no ability to monitor and the like. Yet it seems to me that we should be
establishing the same sort of levels in enforcement in export as well as import,
although this may cause a little problem as far as control in monitoring.
MR. MILLER: If I understand your comment, this is one of the big
advantages, as I see it, of the Codex work. One of the main advantages is that
developing countries which do not have the expertise to do the work themselves
get the advantage of the Codex work.
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SOME PREREQUISITE CONDITIONS FOR THE DETERMINATION
AND EFFICIENT REALIZATION
OF THE ALTERNATIVE CHEMICALS PROGRAM
IN SOME EUROPEAN AND DEVELOPING COUNTRIES
Radojica Kljajic*
Introduction
I deeply appreciate the honour that has been conferred upon me by the
invitation from the Environmental Protection Agency (EPA) to deliver this
presentation, with the opportunity thus provided for a free expression of views
upon some fundamental aspects in connection with pest management and the
rational use of pesticides, i.e. the Alternative Chemicals Program.
Dr. John Buckley said yesterday that we did not start from zero, namely
from the beginning in the field of the rational use of pesticides. He's absolutely
right, but how great are the varying distances from zero in different countries ?
In the United States, like most developed countries, the distance from zero is
much greater than the distance from zero reached in non-developed countries.
Due to the time limit, I would like to draw your attention to a few questions,
starting with definite problems that have been worrying most of the European
countries, as well as some of the developing countries. First and foremost, from
my own country which has very different climatic conditions, different types of
soil, and by its economic progress presents the picture of "a miniature world. "
In this respect, most of the problems, as well as the means of solution, are different
or of a different character. Because the problems are numerous, exceptionally
complex, and interrelated, their solutions must have an organized and constant
character, and realization of the procedures must be coordinated by united action.
Depending on the problem, the action should be of local, regional, national, and/
or international character. The rational use of pesticides and environmental
* Director, Department for Pesticides, INEP, Faculty of Agriculture, University
of Belgrade
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safety has become an everyday preoccupation bothering so far not only the scientists,
producers and applicators of pesticides, competent specialists and responsible
government officials, but also the whole community.
Why the Alternative Chemicals Program ? Is it because of a few persis-
tent insecticides, or because compounds ten times as expensive should replace
them, or because we are not quite sure what should be used as replacements ?
Could the reason be very high toxicity or inadequate efficiency, or the unknown
long-term effects, or the existence of a great number of alternative compounds with
a high number of formulations, or some other reason in the chain of dilemmas. The
problems with pesticides are so innumerable and so constant that both the public
and certain specialists often make statements such that pesticides should simply be
prohibited or that very soon their replacement might be expected by other 'Harmless"
methods.
It is difficult to escape the impression that due to the pressure of
non-informed persons or due to our desperation to achieve some immediate effects,
we often lose the basis for objectivity. We direct our activities mainly to the
consequences and not to the causes of the basic and fundamental problems, although
being important factors of contemporary mankind they strike us directly.
Pesticides and Food. Feed, and Fiber
Topping the list of mankind's problems today is the provision of sufficient
quantities of food and other vital needs for a constantly increasing population. To
be sure, food has been the greatest of man's preoccupations from the remote ages.
It has been the potential motive for all disagreements, disputes, conflicts, and ruins
of many nations. The fact that there are nearly 2 billion starving or food-deficient
humans is overwhelming. This number equals the total world population of 50 years
ago. Although in the developed countries it appears as if hunger has disappeared,
it has never so expressly threatened humanity. There are only 10 countries with
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an excess of food supplies, the United States with approximately 50 percent.
The perspective of further food deficiency during the coming years — there
will be about 7 billion people — is no less fantastic than a vision of an increasing
abundance.
In short, when we talk today about an energy crisis, thinking first of oil, we
must not neglect to consider the significance of the shortage of food, another
important source of energy. This should be particularly stressed because the
total area on which the world population exists is mainly constant which means
that production will have to be intensified by all available means, and we will have
to recognize that the byproducts and uncontrolled application of some production means
may imperil the existence of man.
To what extent the solution of these problems could be simplified depends
primarily on the direction of mankind's efforts. In particular it depends on its
scientific, technical, and technological achievements, as well as on the engagement
of all social and economic factors which may contribute to any extent toward an
organized solution, such as this Symposium.
Various pests actively and persistently cause a decrease in food production
by one quarter, one third, or even one half or more. That means that every fourth,
third, or second farmer works for the existence of such pests. In fact, they represent
the only "competitors " to humanity in the production and utilization of raw materials
and the production of other goods. Their constant presence during the process of
production, storage, and traffic drastically decreases an enormous food potential.
For these reasons, pest control has the character of a constant and
continuous fight, with man and numerous useful organisms on the one side and
over 15 thousand harmful biological agents on the other side. In order to lessen
the losses in this continuous "battle, " man has been employing the most up-to-date
scientific, technical, and technological achievements. Man does so not only to
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diminish the quantitative and qualitative losses, but also to fight the insects,
rodents, and other pests in urban settlements and recreational localities.
Due to the fact that the "enemy" acclimatizes to new conditions, man is
also forced to develop his strategy and tactical measures and weapons against pests,
keeping in mind the presence and necessity of saving the normal growth and
development of a great number of useful organisms within various ecosystems.
Chemical Methods as Part of the Other Pest Control Methods
The thesis on eradication of harmful species cannot be accepted as a
scientific basis. In most ecosystems, some harmful species are always present.
Any measures applied in agriculture, forestry, animal husbandry, food industry,
hygiene, urban settlements, and recreation centers directly or Indirectly affects
biological agents, thus intensifying or preventing their appearance and harmful
effects.
Therefore, numerous and different methods have been applied in this
respect which can be grouped as biological, mechanical, physical, and chemical.
Biological Methods
These include the selection and/or creation of resistant varieties of
species and the regulation of their cultivated growth in order to remove or to
inhibit the appearance and spreading of pests. In some cases antagonistic phenomena
produced in the laboratory or industrially are used against individual enemies —
predators, parasites, and their metabolites.
It is usually understood that under biological methods only part of the
definition, the creation of resistant varieties, is considered. I believe, however,
that this is inadequate and scientifically untenable, since the selection and creation
of resistant species and hybrids in plants and animal species, as well as the regu-
lation of their cultivation, is being widely applied with exceptional significance.
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Logically, in such cases failures are possible but they should not be
exaggerated and their positive effects should not be neglected. In cases of
antagonistic phenomena, reverse actions should be undertaken. Since
practical application is not as widespread at present as the use of resistant
species, potential effects of placement in ecosystems could be exceptionally
significant. The question is in genetic manipulation, which could be more
dangerous for ecosystems than some toxic or persistent pesticides.
Mechanical Methods
By man's activity and the use of certain tools and technical means,
biological agents may be directly destroyed, ecological conditions made unsuitable
for their development and propagation, or in the case of their appearance, their
harmful effect diminished.
This group of methods has been widely applied and is found to be of
exceptional importance in a variety of areas including soil preparation, early
planting of crops, destruction of crop residues, tillage, destruction of volunteer
plants, mechanical harvesting, etc.
Similar to crop residues after mechanized picking, all other measures
and procedures, as well as solid waste accumulation and bad sanitation conditions
in urban settlements can be the source and/or stimulus for propagation of rodents,
insects, and other pests.
Physical Methods
By means of electromagnetic waves of different energy, i. e., thermal,
electric, sound and ultrasound, visible and ionizing radiations,direct or indirect
control is being carried out, or at least such ecological conditions are realized
in which harmful organisms cannot develop.
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The opinions related to this group of methods are often different,
resulting in underestimation and neglect of their significance and role. They
are rather widely represented by disinfection; sterilization; pasteurization;
temperature regulation in storehouses, cooling houses, and refrigerators; moisture
regulation, etc.
Chemical Methods
By means of the application of different compounds and their combin-
ation, pests may be controlled either directly or indirectly. Since mechanical
methods and most of the biological and physical methods are actually agrotechnical,
zootechnical, or some other measure or procedure which does not guarantee success,
there is a necessity for intervention by chemical methods.
It should be emphasized that the further progress of science, techniques,
and technology will contribute to the discovery of some new methods and to the
development of the existing ones in all four groups of methods. Only by correct
choice and application can these give, with the least effort and risk, the most benefit.
Accordingly, each of these methods, including chemical, must be rationally
applied, as should be the case with other achievements of mankind.
Choice of Pesticides and the Alternative Chemicals Program
Certain benefits in food and other goods production, as well as
successful vector control could not be imagined without pesticides. However, the
protection of food stocks and other goods with poisons is a two-edged sword, which
is very efficient in the hands of instructed, trained people, both otherwise very
dangerous or even fatal. Isn't this also the case with other numerous achievements
of our civilization?
The general impression is that our activities, especially in some
European and developing countries, have not been adequately concentrated in this
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direction. We have probably been occupied too much and too long with discussions
on DDT and other persistent insecticides, although it is somehow logical, as
they are persistent and their pathways can be relatively easily traced. Meanwhile,
what about the hundreds of other compounds and potential problems which are
present or ready to appear with their short- or long-term effects, which are
of exceptional importance for their choice and application. They are easily
diluted, less persistent, and more difficult to trace, but this does not mean that
exponential consequences of pollution of the air, water, soil, and living organisms
and the effects on some ecosystems are automatically solved. Beyond numerous
papers on this subject, our knowledge is sparse and not really adequate. Let me
mention the problem of resistance.
It is a well known fact that all living organisms have the ability to
adapt to changed environmental conditions. This is actually the basis of the
evolution of living organisms. Accordingly, resistance is a general biological
phenomenon and the intake of toxic matters including pesticides into the biosphere is
a significant ecological factor. Resistance, up to the present, has been established
in insects, mites, fish, rodents, pathogens, and weeds. The acquired and inherited
properties are in question. In this respect, the phenomenon is exceptionally
complex, not only from the scientific but also from the practical point of view. On
this occasion I will mention only three examples:
It is known that the potato beetle, Leptinotarsa decemlineata, after
7 to 14 generations multiplies its resistance to DDT 10 times in comparison to a
normally sensitive population. It has been evaluated that control is not efficient
if the index is higher than 3.
In my Department, the resistance of the Colorado potato beetle to 6
insecticides was investigated in Yugoslavia, and it was established that the index
approximates 88.2, namely the Id-p line runs up to 1.47 in normally sensitive
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and up to 0.69 in highly resistant populations. Our laboratory experiments
showed that the resistance index in resistant populations was as high as 389.
In the house fly, Musca domestica, the resistance appeared after 30
generations. During the following 41 generations it is unchangeable, and after
that it gradually decreases. Even in this case the genetically disturbed population
becomes rapidly resistant to new insecticides. However, the problem is even
more complex owing to the possibility of cross- and multi-resistance.
The ancient dream of the plant pathologists and agriculturists was to
get systemic fungicides. This has finally been achieved. The problems of
serious resistance were not known before in this field. Recently, there have been
cases that after 1- or 2-year applications of certain compounds, some resistant
biotypes appeared. For example, powdery mildew, Sphaerotheca spp, to Ethrimol,
a number of species, including Botrytis spp., to Benomyl, and similar cases.
These phenomena may have serious implications. Therefore, in the planning
and realization of the Alternative Chemicals Program, due attention must be paid
to the problems of resistance such as early detection, previously checked intro-
duction of new compounds in determined fields, constant control and timely
replacement with other compounds, and successive application.
It is important to stress that the application of some other chemical
methods such as the application of attractants, repellents, bait, sprays, juvenile
hormones, etc., carries in itself certain complexities and potential complica-
tions which make us responsible not only for application, but also for propagating
the perspectives and orientation.
Factors Influencing the Efficiency and Toxicity of Pesticides
The rational choice of alternative chemicals cannot be realized without
an awareness of the basic factors influencing the efficiency and toxicity of pesticides.
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Namely, the complex and complementary activity of pesticides may be stipulated
or it may have a reflexive effect with the whole series of factors of abiotic and
biotic character.
In order to be cognizant of the complex action of pesticides and to
minimize contamination of the air, water, soil, and living organisms, as well as
to achieve the most successful suppression of harmful organisms, it is necessary,
at least in short, to point out the basic groups of objective factors. This is
important because it could help in the work of establishing the causes and no
less in determining the consequences of a non-rational application of pesticides.
Among the factors on which the synchronized program of the application
of pesticides should be based are the following:
1. The basic characteristics of plants and animals, such as the genotype
and phenotype characteristics of the species, varieties and hybrid plants, namely,
the species in all stages of growth and development essentially affect the ripening,
adhering, retaining,and degradation of pesticides on the surface of an organism.
They affect as well the degree of penetration, translocation, decomposition, and
transformation into other compounds, which are sometimes even more toxic than
the pesticides themselves.
2. Pests react specifically to the activity of pesticides because of
the various phenotype and genotype characteristics of each species or its lower
biological category in all stadiums or development phases. The choice of
pesticides must be scientific as well as its concentration, the applied amount,
and the method of application. This is especially important in regard to the
need to know its mode of action and the appearance and disappearance of resistant
forms.
3. Physicochemical and technological properties of pesticides (the
structure of the active substance and ingredients, their compatibility, solubility,
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evaporation, hygrosoopy, viscosity, the size and shape of particles, electrostatic
potential) have an impact upon the dispersion of pesticides in space and upon the
specific toxicity toward each pest individually or an entire plant species.
4. Mechanical and technical characteristics of equipment (e.g.,
motion, speed, effectiveness of mixing suspensions and emulsions, the con-
struction and shape of dispersion, pressure, velocity of particles, equipment
temperature, and other characteristics) act on the uniformity of pesticide
dispersion in space, pesticide effectiveness, and toxicity.
5. Climate and microclimate factors — air represents the largest •
part of the environment around the organism we are protecting, the biological
agents we are holding back, and the pesticides we are applying. Therefore,
humidity, temperature, air speed and direction of movement, and atmospheric
pressure have a great effect on both the dispersion and the dynamics of degradation
•
and transformation, as well as on the growth and development of cultivated
organisms and pests.
6. Soil is the basic recipient of the direct or indirect stocking of
pesticides. Its characteristics, such as pH value, contents of organic matter,
sand, clay, ion-exchange ability, biokinetic relations, and others, also have a
complex impact both on migration and degradation of pesticides, i. e. the degree
of their toxicity, and on the growth and development of plants, various useful
organisms, and pests. Although the above factors are presented in my paper
separately, they are nevertheless necessary to mention in regard to efficiency
and toxicity, and therefore have to be adequatly treated and solved*
For a clear understanding of these numerous factors which are
very complex and interrelated, we can use a layman's interpretation by intro-
ducing symbols.
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The production, distribution* and application of each pesticide may be
regarded as the "movement of a vehicle" along a traced road from the industrial
production, stocking, distribution, application in protecting the food fund 'food,
feed, and fiber), from preparing seeds and soil to the harvest or picking time
respectively, then to stocking, manufacturing, and consumption. The "vehicle"
moves in definite forms to the organism that is being protected, where it stays for
a short time, holds the existing pests back with more or less success, sometimes
even affects the living processes of useful organisms, turning them into other
forms, interacts with other compounds, decreases or increases toxic properties,
and/or continues its "trip" through the plant and animal products and water to man.
Since these traced roads or rather "road networks" are jammed
with a large number of completely different pesticides and related compounds
in the environment from other sources with which they can interact, the creation
of "roads" and "vehicles" must be scientifically elaborated and constructed
of good materials. At the same time, traffic regulators must be entrusted to
trained and qualified persons who will work and study hard and constantly, and pay
full respect to all engaged, irrespectively of the "section" they are in. The
activity of the "traffic" must be based on synchronized, regulated, and coordinated
programming. Otherwise, the "trip" of pesticides will have to follow either an
unfinished "network" or only certain '^sections" using bad "vehicles" and will
become a "traffic chaos."
Importance of Education
Although we are generally aware of the great importance of education,
there is an impression that we do not have enough strength or that we do not pay
enough attention to these problems.
We are witnesses or participants at numerous national and international
meetings in Europe and with United Nations Agencies and are exposed to a great
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number of scientific publications on general or very specific scientific problems,
which is exceptionally positive. However, this is not the case with education
problems. The work to reform our educational plans and programs concerning
all the grades of education, has not yet found its adequate place. But the
consequences are man-sized. I shall quote some examples. The application
of herbicides increases from year to year. In Yugoslavia, for example, it has
Increased more than five times in the last 10 years (1964-1973). In Finland in
1973, herbicides made up 90 percent of all applied pesticides in active ingredients.
Also, in this country, the monetary value of herbicides sold was 58 percent, that
of insecticides, rodenticides, etc. was 36 percent, and the value of fungicides
was 6 percent. The proportion of herbicides increased continuously, being
20 percent in 1957, 38 percent in 1965, and 50 percent in 1968.
ij Illustrations similar to those in Yugoslavia and Finland could be quoted
from other European countries as well. However, because of the main orientation
on the problems of insecticides, especially on persistent ones, our knowledge
about the potential short-term or long-term effects of herbicides is absolutely
insufficient. Among the non-informed people the idea has been formed that herbicides
are almost completely harmless and that they cannot have visible bad effects.
From year to year, there is a constant increase in the consumption
of pesticides by town inhabitants in gardens, small fields, as a hobby or extra
earning, in flats, recreation centres and other places. How much do they know
about pesticides ? Often not very much or nothing. There are even tragicomic
cases when some people use spray in order to kill only 1 or 2 files, mosquitoes,
or some other insects to protect a few pots of flowers, or to spray the bedroom, •
bed linen, and what is even worse, their own body, to protect themselves from
the mosquitoes.
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With regard to the fact that the population is very heterogeneous
according to the degree and profile of education, they are often inclined to
experiment and to Introduce innovation, but they underrate invisible danger
at the moment. Therefore, their training is more complicated than that of
applicators, users, and farmers whose lives directly depend on production.
The production in which the pesticides are used, such as vineyards, amounts
to 35 to 40 percent of annual expenses.
It is hard to expect, however, more prominent progress in the
field of education, as the students of agriculture as well as forestry gain little
information about the prerequisites of the rational application of pesticides and
even less on environmental safety. The students of medicine, veterinary science,
economy, law, sociology, etc. are informed about this even less.
A special problem during education is an insufficient humanitarian
base of professional orientation. That is why with some future specialist there
is an intensified craving for material effects, often only for a short period.
This short sightedness and this blindfolded egoism which is governed by the
motto "after me a disaster," could present irreparable damage to the ecosystems
in which the man lives.
Finally, it is necessary as quickly as possible to pay maximum
attention to educational problems from the point of the rational use of pesticides
and environmental protection and safety. This should be carried out at all
levels, from kindergarten children to post-doctoral students, including various
short courses for the education of adults regardless of their function — par-
liament, government authorities, university professors and teachers, journalists,
lawyers, medical doctors, and others if their activity has or can have any Influence
on solving the problems of the rational use of pesticides and/or environmental
safety.
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It is an old proverb 'better prevent than cure" and that holds good
for pest management and the rational use of pesticides too.
DR. ARNOLD ASPELIN: I would just like to comment on the need for a
broadened, multidiscipllnary approach to the international efforts such as have been
discussed today. Throughout these sessions I've gotten the feeling that social and
economic values were not addressed very squarely. Maybe this was done subconsciously
or even consciously in some cases. It is not too difficult for me to understand why
we can't get agreement among nations on numbers such as under Codex. Economists
and other social scientists might well be able to provide some useful insights into
some of these issues which apparently are being handled mostly by physical and life
scientists who early on got into the pesticides area. So I would just like to make
an appeal for a broader social science approach to some of these things.
Dr. CHARLES KRISTER: Professor Kljajic, since you brought it up, I'd
like to take advantage of the opportunity to extend either your comments or perhaps
clarify some of the remarks about benomyl. Was this a laboratory test in which
resistance occurred, or was it actually resistance out in the field? Was this a
field plot where resistance occurred or was it a laboratory screening in which
resistance occurred ?
DR. RADOJICA KLJAJIC: The cited examples have been taken from the
literature and are related to the results obtained both in vitro and in vivo. .
DR, KRISTER: Two comments that I would like to offer. One is that in
our experience out in the field where resistance has occurred, the resistant
organisms were actually there in the field. Secondly, where there has been problems
in connection with use of benomyl on any particular crop, the resistance can be handled
by a combination of maueb and benomyl, or alternate treatments of benomyl and maueb.
Does this confirm what has been found in your experience ?
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With regard to the fact that the population is very heterogeneous
according to the degree and profile of education, they are often inclined to
experiment and to Introduce Innovation, but they underrate invisible danger
at the moment. Therefore, their training is more complicated than that of
applicators, users, and farmers whose lives directly depend on production.
The production in which the pesticides are used, such as vineyards, amounts
to 35 to 40 percent of annual expenses.
It is hard to expect, however, more prominent progress in the
field of education, as the students of agriculture as well as forestry gain little
information about the prerequisites of the rational application of pesticides and
even less on environmental safety. The students of medicine, veterinary science,
economy, law, sociology, etc. are informed about this even less.
A special problem during education is an insufficient humanitarian
base of professional orientation. That is why with some future specialist there
is an intensified craving for material effects, often only for a short period.
This short sightedness and this blindfolded egoism which is governed by the
motto "after me a disaster, " could present irreparable damage to the ecosystems
in which the man lives.
Finally, it is necessary as quickly as possible to pay maximum
attention to educational problems from the point of the rational use of pesticides
and environmental protection and safety. This should be carried out at all
levels, from kindergarten children to post-doctoral students, including various
short courses for the education of adults regardless of their function — par-
liament, government authorities, university professors and teachers, journalists,
lawyers, medical doctors, and others if their activity has or can have any Influence
on solving the problems of the rational use of pesticides and/or environmental
safety.
193
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It is an old proverb "better prevent than cure" and that holds good
for pest management and the rational use of pesticides too.
DR. ARNOLD ASPELIN: I would just like to comment on the need for a
broadened, multidlsciplinary approach to the international efforts such as have been
discussed today. Throughout these sessions I've gotten the feeling that social and
economic values were not addressed very squarely. Maybe this was done subconsciously
or even consciously in some cases. It is not too difficult for me to understand why
we can't get agreement among nations on numbers such as under Codex. Economists
and other social scientists might well be able to provide some useful insights into
some of these Issues which crrparently are being handled mostly by physical and life
scientists who early on got into the pesticides area. So I would just like to make
an appeal for a broader social science approach to some of these things.
Dr. CHARLES KRISTER: Professor Kljajic, since you brought it up, I'd
like to take advantage of the opportunity to extend either your comments or perhaps
clarify some of the remarks about benomyl. Was this a laboratory test in which
resistance occurred, or was it actually resistance out in the field? Was this a
field plot where resistance occurred or was it a laboratory screening in which
resistance occurred?
DR. RADOJICA KLJAJIC: The cited examples have been taken from the
literature and are related to the results obtained both in vitro and in vivo. •
DR. KRISTER: Two comments that I would like to offer. One is that in
our experience out in the field where resistance has occurred, the resistant
organisms were actually there in the field. Secondly, where there has been problems
in connection with use of benomyl on any particular crop, the resistance can be handled
by a combination of maueb and benomyl, or alternate treatments of benomyl and maueb.
Does this confirm what has been found in your experience ?
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DR. KLJAJTC: The cited examples, including benomyl, are illustrations
of the complex and complicated problems of the resistant pests not only to the
"first" but also to the "second" and "third generation" of pesticides. My point
was that the application of every new and old compound must always be under
continuous scientific supervision.
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NATIONAL ENVIRONMENTAL PESTICIDE MONITORING PROGRAM
Dr. William S. Murray*
Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) as
amended, the Environmental Protection Agency (EPA) is responsible for
designing and implementing a National Pesticide Monitoring Plan. A plan is
currently in the review stage, but an existing National Pesticide Monitoring
Network has been operating for several years and is coordinated by an interagency
body called the Monitoring Panel of the Federal Working Group on Pest Manage-
ment. In addition to EPA, the agencies represented on this panel are the Food and
Drug Administration which is responsible for monitoring food and feed, the
Department of Agriculture which is responsible for monitoring red meat and
poultry, the Fish and Wildlife Service of USDI which monitors freshwater fish
and various birds, and the Department of Defense which has its own monitoring
program on military reservations.
The other environmental components are being monitored by the Environ-
mental Protection Agency. They include air, freshwater, estuaries, the oceans,
soil, crops associated with the soil, and numan tissue. These programs are the
direct responsibility of the Ecological Monitoring Branch in the Technical
Services Division of the Office of Pesticide Programs.
During this talk, I will describe our monitoring systems and special
projects capability.
All monitoring systems operate through three basic phases:
• Field collection of the samples
• Laboratory chemical analyses of these samples
• Analysis and interpretation of the data
*Director, Technical Services Division, Office of Pesticide Programs, U. S.
Environmental Protection Agency
Preceding page blank
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I will use the National Soils Monitoring Program to describe each of these
three phases and then only describe the field collection phase for the remaining
systems, since that is the only different phase among the programs.
The National Soils Monitoring Program
The National Soils Monitoring Program was designed to collect statistically
valid samples from the nation's cropland, noncropland, and urban areas. A
total of 13,300 sites In the cropland and noncropland areas were identified, with
1/4 of this number to be sampled each year. The design proved too ambitious for
the available resources and noncropland is no longer sampled. The number of
cropland sites sampled since the program was instituted has ranged from 1500 to
1700 per year. Since the program has not been able to consistently cover the
whole nation, a new modified design will be developed for FY1976. To date,
*
cropland soil has been sampled in 45 states; noncropland soil has been sampled
**
in 28 states; and 37 standard metropolitan statistical areas have been sampled
for our urban soil monitoring program (Figure 1).
Soil samples are collected using a soil core 3 inches deep by 2 inches in
diameter. A cropland sampling site is usually made up of 10 acres with 50 soil
cores collected over that 10 acres on a 5 x 10 grid. In the urban areas, this is
modified to use a 50 x 50-foot plot and a 4 x 4-grid.
After the soil samples have been collected, they are screened three times
v
through 1/4-inch mesh screening and a 2-quart subs ample is taken. Equipment
is carefully washed to ensure that there is no possibility of cross-contamination
between sampling sites. For each site a map is made to enable us to go back to
*A11 but Montana, Kansas, Texas, Alaska, Hawaii
'""'All but Alabama, Arkansas, California, Colorado, Florida, Louisiana,
Minnesota, Mississippi, Missouri, Nevada, New Mexico, North Dakota,
Oklahoma, South Carolina, South Dakota, Utah, Oregon, Montana, Kansas,
Texas, Alaska, Hawaii
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Figure 1
Urban Soil Sampling Sites
KY 70 FY 71 (confd) FY 7H
Bukerafleld, Ca. Grand Rapids, Mich. Des Moines. Iowa
Camdcn,N.J. Greenville, Mass. Fitehburg, Mass.
Houston, Tex. Sikeston, Mo. Lake Charles, La.
Manhattan, Kan. Portland, Ore. Pittsburgh, Pa.
Miami, Fla. Philadelphia, Pa. Reading, Pa.
Milwaukee, Wis. Charleston, S.C.
Salt Lake City, Utah Memphis, Tenn. FY 74
Waterbury, Conn. Richmond, Va. Evansville, Ind.
Cheyenne, Wyo. Greenville, S.C.
FY 71 Pittsfield, Mass.
Mobile, Ala. FY72 Tacoma, Wash.
Wilmington, Del. Baltimore, Md. Washington, D. C.
Honolulu, Hawaii Gidsden, Ala
Sioux City, Iowa Hartford, Conn. FY 75
Augusta. Maine Macon, Oa. San Francisco, Ca.
Newport News, Va. Pine Bluff, Ark.
Gary, Ind.
Durham, N. C.
Springfield, 111.
that site 4 years after the original sampling to take trend data. For cropland
sites, in addition to a soil sample, a crop sample is collected when available.
The following information is also obtained from the farmer:
• The crops grown on the site in addition to those sampled
• Irrigation used, if any
• The number of inches of irrigation
• Pesticides used
• Crop the pesticide was used on
• Formulation that was applied
• Pounds of active ingredient applied
• Method of application
After the sample has been collected in the field, it is sent to our central
receiving laboratory at the Mississippi Test Facility. Here the samples are
analyzed using primarily gas liquid chromatography. There is also a wide range
of confirmatory instruments available for use, including atomic absorption
spectrophotometry, liquid chromatography, and mass spectrometry. I'll go into
more detail about the laboratory itself shortly.
After the chemical analyses have been completed, the resulting data are
returned to the branch headquarters in Washington where they are statistically
analyzed using either small desk-top computers such as the Hewlett Packard,
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9100-B, or larger computer support programs. Presently all five of our monitor-
ing programs are computerized.
The National Estuarine Monitoring Program
The objective of the National Estuarine Monitoring Program is to determine
pesticide levels in fish in estuaries. Approximately 113 estuaries are sampled
for two trophic levels of fish: herbivorous and carnivorous. Collections are
made twice a year. Sampling teams attempt to collect only young of the year,
since mis age group indicates the current contamination load in the estuary.
The samples are shipped to the Pesticide Monitoring Laboratory at Bay St. Louis,
Mississippi for analysis.
Originally, this program sampled crustaceans and shellfish, which are good
indicators of recent contamination. They are, however, able to purge themselves
of residues within a fairly short period of time. Since insufficient resources
were available to continue the program of monthly collections of shellfish, the
program was redesigned in FY 1972. Fin fish were selected since they retain
pesticide residues longer, are mobile, and are therefore a better overall Indicator
and integrator of pesticide pollution in an estuary.
The National Human Tissue Monitoring Program
The purpose of the Human Monitoring Program is to determine, on a
national scale, the incidence and level of exposure to pesticides experienced by
the general population and to identify changes and trends in these parameters
when they occur. Pesticide residues and their metabolites mat are detected
reflect man's total exposure to these chemicals and his physiologic ability to
handle them. This program was initiated in 1967 by the Pesticides Programs,
Communicable Disease Center of the Public Health Service, and was transferred
to the Environmental Protection Agency upon its creation in 1970.
The major thrust of the program is the collection and chemical analysis of
samples of human adipose tissue. These are obtained through cooperating
pathologists in 75 collection sites selected according to an experimental design
in the conterminous 48 states (Figures 2 and 3).
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Figure 2
National Human Monitoring Program
Collection Sites by State
FY 1975
Alabama (6)
Mobile
Tuscaloosa
Arizona (8)
Phoenix
California (9)
Bakersfield
Glendale
Lakewood
Long Beach
Los Angeles - 2
National City
San Francisco
Colorado (8)
Denver
District of Columbia (5)
Florida (5)
Hialeah
Panama City
Tampa
Illinois (3)
Chicago - 3
Oak Park
Indiana (3)
Evans ville
Indianapolis
Iowa (4)
Iowa City
Kansas (4)
Salina
Wichita
Kentucky (6)
Louisiana (7)
New Orleans
Maryland (5)
Baltimore
Massachusetts (1)
Boston
Pittsfield
Westfield
Worcester
Michigan (3)
Bay City
Detroit
Wyandotte
Minnesota (4)
St. Louis Park
Missouri (4)
St Louis
Nebraska (4)
Omaha
New Jersey (2)
Hoboken
New York (2)
Buffalo
Jamestown
New York City - 7
Troy
North Carolina (5)
Charlotte
Winston-Salem
Louisville
201
Ohio (3)
Cleveland
Columbus
Mansfield
Parma
Toledo
Oklahoma (7)
Enid
Oklahoma City
Oregon (9)
Eugene
Pennsylvania (2)
Erie
Hazelton
Philadelphia
South Carolina (5)
Anderson
Greenville
Tennessee (6)
Kingsport
Memphis
Texas (7)
Dallas
El Paso
Houston
San Antonio
Utah (8)
Salt Lake City
Virginia (5)
Norfolk
Petersburg
Washington (9)
Tacoma
Wisconsin (3)
Beloit
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Figure 3
Chemicals Detectable In the National Human Monitoring Program
Multi-Residue Analysis of Adipose Tissue
Chemical Limit of Detectablllty in PPB
o,p'-DDE 20
p.p'-OOE 10
o,p'-DDT 20
p.p'-DDT 20
p.p'-DDD 20
a-HCH 10
B -HCH 20
Y -HCH (lindane) 10
6-HCH 10
Aldrln 10
Heptachlor 10
Heptachlor epoxlde 10
Dieldrln 10
Endrln 20
Mirex 100
Oxychlordane 20
Trans nonachlor NA*
Polychlorinated blphenyl 800
Hexachloroben.".ene 4
*Not available at this foe
' A proportionate stratified sampling design is followed for selection of cities
from which samples are collected. The number of cities needed in each census
division is determined based on the total population in that division. This type of
design provides data which are representative of the general population. For
each collection site, an annual sample quota reflective of the demographic distri-
bution of that particular census division is established.
Adipose tissue collected by cooperating pathologists is from postmortem
examinations and from specimens previously removed during therapeutic surgery.
Information recorded for each tissue sample analyzed includes age, sex, race,
height, weight, pathological diagnosis, occupation, and geographic residence.
Since the objective of the program is to reflect the pesticide burden in the general
population, samples are not collected from victims of known or suspected pesticide
poisonings, from chronically ill patients, or from patients institutionalized for
extended periods.
All analyses are conducted by contract laboratories using only methodologies
specified by the program. These laboratories are equipped with gas-liquid
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chromatographs with electron capture and other detectors. They are required to
maintain acceptable performance levels in the Interlaboratory Quality Assurance
Program moderated by EPA's Pesticides and Toxic Substances Effects Laboratory.
This laboratory also provides technical consultation for the analytical portions of
the program. All samples are analyzed for selected chlorinated hydrocarbon
insecticides and polychlorinated biphenyls using a multiresidue approach. This
procedure is capable of detecting metabolites as well.
Other human substances such as urine, blood, and milk are collected
for analysis to detect some of the newer classes of pesticides. Currently a
special project measuring organophosphate insecticide metabolites in urine is
underway. I'll discuss that further in a moment.
The National Water Monitoring Program
A National Monitoring Plan for monitoring pesticide residues in fresh
water was published in the June issue of the 1971 Pesticide Monitoring Journal.
This plan had never been implemented. However, a cooperative program was
eventually worked out between the U. S. Geological Survey and the Environmental
Protection Agency, which was initiated in the fall of 1973. The Geological Survey
collected the water samples at 132 sampling sites in 17 major river basins. We
conducted the chemical analyses. Originally the design called for four water
samples and two sediment samples to be collected each year from each station.
However, only one paired collection of sediment and water was made in the first
year of sampling. In FY1975, all planned collections will be undertaken.
The National Air Monitoring Program
When one considers pollution in air, pesticides do not usually come to
mind as being the primary pollutant. However, in certain situations such as
during the height of the spray season in the Wenatchee Valley, pesticides in air
can be a serious problem.
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The National Monitoring Program for Pesticides in Air, which was in
existence from 1970 through 1972, detected low levels of a large number of resi-
dues.
The sampling device which was used in that program was an impinger
system. Basically, with that system, an air stream was bubbled through an
ethylene glycol solution and the pesticides contained in that air stream were par-
titioned into the ethylene glycol. Under consideration for the future air program
is a high volume air sampler. The advantage of the high volume air sampler over
the impinger sampler is that it is a simpler machine, easier to operate, and it
samples a larger volume of air to impinge pesticides onto a substrate. Therefore,
the analytical sensitivity required to support this air sampling device is much
less. In order to determine the best method of sampling air, both these instru-
ments are currently undergoing extensive field evaluation. Upon completion of
this study, the national air program will be redesigned and reinstituted.
The Ocean Monitoring Program
The oceans are generally considered an important sink for many persistent
pollutants, and to date there has been no systematic monitoring of the oceans for
pesticide residues on a continuing basis. The National Marine Fisheries Service
approached us, suggesting that a cooperative program might be established
between their organization and the Environmental Protection Agency. Basically,
they agreed to supply ship time and collect fish samples at sea; our Agency would
then do the chemical analyses and supply other monitoring support. Knowing that
the Agency could not afford to pay the cost of ship time, we took advantage of this
situation. In FY 1974, fish samples were collected on six ocean cruises on both
coasts of the United States. The program at this time is viewed strictly as a
pilot program. Its effectiveness will be evaluated and further decisions will be
made as to whether it should be continued and possibly expanded.
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Feed Monitoring
As mentioned earlier, the Food and Drug Administration is responsible
for monitoring feed. However, after the episode with dieldrin contamination of
chickens this spring, we were approached by Or. Axelrod who suggested that a
comprehensive pesticide monitoring program be established for animal feed and
feed components. When FDA was contacted by Ecological Monitoring Branch
representatives, they proposed an expanded cooperative feed monitoring program
between FDA and EPA. This has been agreed to in principle by both agencies;
negotiation of the actual details is still ongoing. Very tentative plans are for the
collection of 750 samples in FY 1975, with an increase to 1,000 in FY 76; these
samples would be analyzed at our MTF Monitoring Laboratory.
MTF Pesticide Monitoring Laboratory
This is an appropriate point to make additional mention of the Pesticides
Monitoring Laboratory located near Bay St. Louis, Mississippi at the old NASA
Mississippi Test Facility. At this modern laboratory of ours, there are an
additional 24 persons including 10 chemists who provide the chemical support for
the soil, water, and estuarine system, as well as for the various Special Ecological
Projects. This amounts to an incoming sample load of about 6,000 samples per
year and well over 12,000 analyses. Most samples are routinely analyzed for
chlorinated hydrocarbon and organophosphate pesticides including the following.
I'll try to add trade names where they may be helpful (Figure 4). For cropland
soil, arsenic and trlazine analyses are also conducted. Heavy metal analyses
for lead, cadmium, arsenic, and mercury are being run or will be performed
on estuarine samples and urban soil samples.
In the future we hope to add a multiresidue method for carbamates. Such
a method is now under investigation and development by our supporting research
laboratory.
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Figure 4
Compounds Routinely Monitored for Organochlorine Compounds
T
Alachlor (Lasso )
Aldrin
Benzene Hexachloride
Captan
Chlordane
T
Chlordecone (Kepone )
Chlorinated Phenoxy Esters
T
Chlorobenzilate (Acaraben )
DCPA (DacthalT)
DDT's (o,p'-DDT;p,p'-DDT'
o.p'-DDE; p,p'-DDE; p,p'-TDE
Dicofol (KelthaneT)
Dieldrin
Dithianon (Dicarbonitrile)
DMC
T
Endosulfan I (Thiodan )
Endosulfan II
Endosulfan Sulfate
Endrin
Endrin Aldehyde
Endrin Ketone
Heptachlor
Heptachlor Epoxide
T
Isobenzan (Telodrin )
Lindane
Methoxychlor
Mirex
Ovex
PCB's (Polychlorinated Biphenyls)
PCNB (Pentachloronitrobenzene)
T
Propachlor (Ramrod )
T
Terpene Polychlorinates (Strobane )
Toxaphene
T
Trifluralin (Treflan )
Organophosphorous Compounds
Azinophosmethyl (Guthion )
T
Carbophenothion (Trithion )
T
Chlorpyrlfos (Dursban )
T
DEF (Degreen )
T
Demeton (Systox )
Diazinon
T
Dloxathion (Delnav )
T
Disulfoton (Di-syston )
Dyfonate
EPN
Ethion
Ethyl Parathion
FolexT)
Malathion
T
Methyl Demeton (Meta-systox )
Methyl Parathion
T
Phorate (Trimet )
T
Ronnel (Korlan )
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The recent addition of automated gas chromatograph injection equipment
should allow the laboratory to increase its production. We are currently in the
process of getting this equipment geared into our routine production.
Special Ecological Projects
In addition to the ongoing ambient monitoring networks, we also conduct
studies we refer to as Special Ecological Projects. In the past, these were
short-term monitoring studies on particular residue problems, initiated as a
result of regular monitoring operations or at the request of another office within
the Office of Pesticide Programs.
A study of the herbicide propanil and its metabolites in rice and rice soils
exemplifies this type of effort. The metabolite TCAB has a similar chemical
structure to that of a carcinogen and has been detected in rice soil as a result of
normal use of propanil. This metabolite, an azobenzene compound, had been
shown to form in laboratory tests in soil, but had never been detected from actual
field usage. All samples have been collected for this project and they are awaiting
chemical analysis at MTF. This study was initiated at the request of the Criteria
and Evaluation Division.
Another special project is the study of the incidence and levels of organo-
phosphate insecticide metabolites in human urine after a mosquito control
application. Before and after aerial spraying in Dover, Delaware, urine samples
were taken from people residing both in the target area and in a peripheral area.
These samples are presently being analyzed. This type of human monitoring is
of special public health interest, since the population of treated areas is
unavoidably and directly exposed to the insecticides.
One proposed study for the spring of 1975 is a cooperative irrigation
study with the Bureau of Reclamation, which is responsible for providing Federal
aid to irrigation systems. This study would address problems associated with the
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fate and movement of pesticides in irrigation water and should provide valuable
data for both agencies. The design of the study has not quite been initiated, but
samples of water, sediment, soil, crops, and fish will probably be collected.
This project will also impact on EPA's new water legislation as certain large
irrigated areas are considered point-source polluters in terms of pesticides.
Our staff members were primarily responsible for the design and subse-
quent coordination of the collection of samples for the several phases of EPA's
dioxin monitoring effort during FY 1974. In addition, the MTF Pesticides
Monitoring Laboratory ran the extractions of the samples for this project. Branch
personnel were also involved in evaluating the Forest Service's monitoring pro-
gram for the DDT spray project against the Douglas-Fir Tussock Moth in the
Pacific Northwest.
In the past year, the definition and scope of our special projects capability
has been expanded to encompass more situations requiring pesticide monitoring
expertise. Our appraisal of present and future monitoring requirements indicates
that a continuing and increasing demand will be made of the capacities of our
current networks and our special projects. With changes in pesticide technology
and use patterns, our monitoring program will be shaped to continue to be
responsive to Agency needs. In the future we anticipate that monitoring activities
will extend into the following areas.
1. Experimental Permits — The responsibility for monitoring experimental
permits is usually placed upon the Industry or organization making the application.
However, in certain cases, the Agency may find it to its advantage to conduct
monitoring activities either in addition to or in cooperation with the organization
seeking the permit.
2. Emergency Pesticide Use — Monitoring programs would be involved
with requests to the Agency for the use of pesticides on an emergency basis under
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section 18 of the amended law. We would provide technical surveillance over
such applications in terms of ecological effects.
3. Classification and Reclassification of Pesticides — Data from both our
continuing surveillance system and special short-term projects will be used in the
classification and reclassification of pesticides as required by the amended law.
4. Litigation Proceedings — Monitoring information from our established
networks and from special studies continue to be useful for fact-finding, cancella-
tion, and suspension public hearings.
5- Alternative Chemicals Program — Planning for monitoring input into
this Agency program has been underway since its creation. The monitoring
requirements of this program will be varied.
6. Operational Surveillance — Surveillance monitoring does not fall into the
classic definition of pesticide monitoring; it is an area in which we have only
recently become involved. It centers around the development of methods and plans
to oversee special pesticide applications to ensure that these conform to Agency
requirements and environmental impact statements.
Use of Data
Yearly summaries of all the programs and most special projects are
published in the open literature and in internal reports by EPA. The data generated
by our numerous monitoring projects is actively utilized in the Agency and by
others. Data have been requested by parties on both sides for use in the ongoing
pesticide litigations on mirex, aldrin, dieldrln, and mercury. Our personnel have
testified as expert witnesses in several fact-finding, cancellation, and suspension
public hearings.
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In addition, requests for data are received from universities, chemical
companies, and offices of state and Federal government. Since last January,
nearly 300 written reprint requests have been received, mostly from state govern-
ments. A considerable number of inquiries for information and advice are
handled by our personnel.
Most of our findings have dealt with residue levels in various media. Now
that the programs have been conducted for several years, we will be examining the
data to detect changes and trends in pesticide use and residue levels. Also, the
addition of graphic support should aid in conducting and displaying results of
these comparisons. All comparisons will, of course, have to be statistically
based, but visual displays should be particularly helpful to a variety of users of
our data.
The five EPA National Pesticide Programs and those of other agencies need
to have the data from their systems integrated to determine what relationships
exist. The feasibility of such a project is now under investigation in our Agency
as an independent review, and a final report will be completed this winter.
DR. R. R. WHETSTONE: You have discussed monitoring pestidice residues.
Will the program include monitoring of phenomenon rather than pesticides, such
as photosynthesis in the ocean ?
DR. WILLIAM MURRAY: I would like to believe that this lies just ahead.
Certainly we're in the process of making the transition from monitoring residues
to monitoring residues and determining what they mean, in other words, effects
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monitoring. I think what you're referring to is just around the corner. It is going
to require some additional expertise on our staff and some additional support, but
this is certainly very important to us.
QUESTION: There are two questions I'd like to ask. One, have you noticed
any change in trends in amounts of DDT in humans since it's been phased out, and
if not is that to be analyzed as a part of your program? And second, in the case of
the propanil are you taking both plant samples and soil samples from the same
sites ?
DR. MURRAY: The latter answer is yes from both sites. The former
question is a little bit more difficult, and there's an opportunity to get into trouble
here in oversimplifying. Nevertheless there has been a small drop in the amounts
of DDT in the average person's body. The reason I'm being a little careful here
is because it depends on a number of factors including geographic location and some
other demographic parameters, i.e., age, sex, race. So the answer is really
quite complicated, and I'm not prepared to give it in any more detail.
MR. TOM BLUE: With respect to the soil monitoring program and the
collection of data from the farmers as to the types of pesticides used and so forth,
over what time frame do you collect these use data and relate them to what's in
the soil sample ? And do you analyze for all of the chemicals applied over that
time period ?
DR. MURRAY: The soil monitoring program has been going on for 5 years.
To answer your last question, I did read, very briefly of course, the kinds and
numbers of pesticides for which we analyze the soil samples.
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PESTICIDE RESEARCH
IN THE U. S. DEPARTMENT OF THE INTERIOR
Jerry R. Longcore*
I appreciate the opportunity to attend this Symposium on the Alternative
Chemicals Program and to participate in this overview of pesticide research.
In the following, I will present a brief resume of the various agencies of the
Department of the Interior that are engaged in pesticide studies.
The Department's efforts in pesticide research are primarily concerned
with two areas: (1) to evaluate pesticides in the laboratory and the field for their
toxicity, sublethal effects, and hazards from specific uses to fish, wildlife, and
the environment and (2) to gather data required for registration of specific
chemicals — chemicals that are necessary to meet the responsibilities of many
of the land management agencies of the Department.
First, I would like to discuss the pesticide efforts in the Fish and Wild-
life Service and then touch upon the efforts in other agencies of the Department.
Fish and Wildlife Service
Department research efforts in the above mentioned areas are carried
out primarily in the Fish and Wildlife Service, which, in addition to pesticide
research per se, has the responsibility for animal and bird damage control and
thus needs suitable control agents (chemical or otherwise). Wildlife damage to
agricultural crops in some geographical areas Is extensive; fruit and cereal
crops are especially affected. A number of compounds are utilized In the Federal
Fish Hatchery Program, and many other Service agencies need chemicals for
vegetation control or other pest control problems. Under the Fish and Wildlife
Act of 1956, the Service also has the responsibility of Investigating the effects
of polluting substances on fish and wildlife.
*Staff Specialist, Pesticides and Pollutants, U.S. Department of the Interior
Preceding page blank 213
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Because many of the Department's chemical needs are in the so-called
minor-use category (i. e., expected use too small to interest industry in
registering a chemical for a particular use), it must register chemicals through
its own or cooperative efforts with other agencies or industry.
The main laboratories involved in pesticide research and the general
thrust of the research are as follows:
FISH CONTROL LABORATORY
La Crosse, Wisconsin
SOUTHEASTERN FISH CONTROL
LABORATORY
Warm Springs, Georgia
GREAT LAKES FISHERY
LABORATORY
Ann Arbor, Michigan
SOUTHEASTERN FISH CULTURAL
LABORATORY
Marion, Alabama
FISH-PESTICIDE RESEARCH
LABORATORY
Columbia, Missouri
DENVER WILDLIFE RESEARCH
CENTER
Denver, Colorado
Registration of chemicals for fishery
management.
Evaluation of hazard of pesticides to
fish and the aquatic environment.
Registration of chemicals for fishery
management.
Determination of pesticides in Great
Lakes fish.
Evaluation of the effects of pesticides
In fish.
Evaluation of hazards of pesticides in
aquatic environments.
Evaluation of hazards of pesticides in
aquatic environments.
Registration of chemicals for manage-
ment (primarily herbicides).
Evaluation of hazards of pesticides to
wildlife.
Registration of animal damage control
chemicals.
Registration of bird damage control
chemicals.
PATUXENT WILDLIFE RESEARCH Evaluation of hazards of pesticides to
CENTER wildlife.
Laurel, Maryland Registration of bird damage control
chemicals.
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While laboratories collect data for registration, they also obtain informa-
tion on hazards related to the use patterns for which the registration is sought.
However, the Wildlife Research Centers at Denver and Laurel and the Fish-
Pesticide Laboratory at Columbia do most of the studies of the effects of
pesticides on non-target organisms and the environment. In addition to the
laboratories mentioned, 20 Cooperative Wildlife Research Units and 25
Cooperative Fishery Research Units are located at 26 universities and supported
by the universities, the state agencies, and the Fish and Wildlife Service. A
limited number of pesticide studies are conducted at these research units.
The above has covered the why and the where of the pesticide research
in the Fish and Wildlife Service. The question of what is being done can best
be depicted by examples of the two major research thrusts, registration and
ecological evaluation of effects on non-target species.
Registration of Chemicals
Efforts related to obtaining registration data encompass a variety of
studies. These investigations include but are not limited to toxicology,
chemistry, efficacy, uptake and elimination, degradation and identification of
metabolites, and residues.
Examples of chemicals now under study for use in fishery management
include TFM (3-trifluormethyl-4-nitrophenol) with Bayer 73 <2'5-dichloro-4'-
nitrosalicylanilide), a lamprey larvicide; antimycin (an antibiotic substance
produced by Streptomyces spp.), a fish toxicant; certain herbicides (simazine,
diuron, endothall, and dlquat); and Thanite (terplnyl thiocyanoacetate), dylox,
and a number of other compounds, including some used as drugs or therapeutics.
Current efforts in the registration of animal control chemicals include
work on zinc phosphide for control of prairie dogs on rangeland, jack rabbits
(agricultural crops), pocket gophers (crops and forests), voles (agricultural
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crops), ground squirrels (rangeland), and rats (sugarcane); Mestranol, which
Is used as a repellent for white-footed mice In forestry management; and
medroxyprogesterone acetate (a reproductive Inhibitor), which Is needed for
deer control In certain park areas.
Compounds being studied to alleviate bird damage Include avitrol
for blackbird control in sunflowers, sweet corn, sorghum, and field corn;
and methlocarb for blackbird control in sprouting field corn, rice, and wheat
and for control of bird damage In cherries, blueberries, and grapes. Certain
wetting agents are being evaluated for population reduction of blackbirds at
undesirable roost sites. In an attempt to discover species differences that
may be exploited for control purposes, chemical metabolism by liver mlcrosomes
Is being studied In the red-winged blackbird.
Evaluation of Pesticide Hazard
Our evaluations of pesticide hazard to non-target species are based on
broad ecological field Investigations supported by controlled laboratory
experimentation. Included In these studies are certain standard bloassays or
tests of acute toxicity. Current and continuing ecological investigations of
wildlife Include studies of problem chemicals In sensitive and/or especially
exposed species such as black-crowned night herons, other herons, brown
pelicans and associated seablrds, bald eagles, ospreys, bats and Insectivorous
birds, and waterfowl. Ecological studies also Include evaluation of specific
uses of certain chemicals such as toxaphene on rangeland, endrln on pine seeds,
and aldrin and furadan in rice culture.
Laboratory experimentation on the effects of pesticides on reproduction,
behavior, enzyme systems, and on pesticide kinetics (accumulation and loss)
and lethal residue levels are conducted with a number of avion species: mallards,
black ducks, bald eagles, kestrels, bobwhlte quail, coturnix quail, pheasants,
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starlings, red-winged blackbirds, cowbirds, grackels, ringed doves, and
homing pigeons. Experimental colonies of barn owls and black-crowned night
herons will be ready for pesticide studies this coming year.
The following selected research highlights may give an indication of
the variety of studies and elucidate the scope of this pesticide research.
These examples of research findings are typical of work being done at the
Patuxent and Denver laboratories.
Kelthane, an organochlorine acaricide structurally similar to DDT,
increased mallard embryo mortality when females were fed a diet containing
low levels of the pesticide. Mercury (methylmercury) was found to adversely
affect reproduction of mallards, black ducks, and ring-necked pheasants; it
has been found to be highly persistent in duck tissues, but after the moult the
body residues drop conspicuously. Aroclor 1242, when fed in the diet, caused
a thinning of coturnix quail egg shells.
New pollutants have appeared in bird tissues; octachlorostyrene and
related isomers have been identified from a bird sample, and hexachlorobenzene
(HCB's) is occurring in bird and fish species.
Studies of bald eagles found dead in the field have revealed that
enough dieldrin has accumulated in the brain of some individuals to cause
death.
Studies of DDE in free-tailed bats indicate that young bats obtain much
of their DDE via the nursing female's milk. Mortality of young free-tailed bats
reposed in a Texas cave was shown to have been from starvation and not from
pesticide poisoning.
Oxychlordane (a metabolite of chlordane), when tested in several
species of blackbirds, was nearly as toxic as dieldrin; it was accumulative
and persisted in the tissues.
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Parathion, when fed to quail after they had been fed methylmercury,
was found to be more toxic than when used alone. This indicates the potential
problem of multiexposure of organisms to pesticides and other pollutants.
Multienzyme analysis has shown toxicant-specific responses to Ingested
chemicals, and for some enzymes, dose-related responses. Enzymes were
studied in starlings and the chemicals Morsodren, DDE, Aroclor 1254, and
malathion were evaluated.
Our research on pesticides in aquatic organisms, which is carried
out primarily at the Fish-Pesticide Laboratory and its field stations, is done
on those chemicals that meet the following criteria:
1. Pesticides (or other chemicals) that have established uses, either
terrestrial or aquatic, which are considered to be aquatic contaminants already
in the environment.
2. Pesticides that are being considered for aquatic use in resource
management. This research is often in the form of gathering data for registra-
tion.
3. Chemicals that are being commercially registered for uses with
high potential for producing aquatic contamination. These are frequently new
chemicals or new uses of existing chemicals that are being developed for
commercial application.
The goal of the research is to unravel the obscure and subtle over-
all effects of pesticides on aquatic ecosystems. To do this requires a multi-
disciplinary approach involving a team of scientists. The scope of the work
encompasses the following:
1. Acute and chronic toxicity of pesticides to fish and aquatic
organisms.
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2. Influence of environmental factors on toxicity.
3. Bloaccumulation and blotransfers of pesticides in segments of the
aquatic food web.
4. Toxic interaction of pesticides.
5. Pesticide-induced pathology in fish.
6. Effects on metabolism, growth, behavior, nutritional state, and
hormonal response of fish.
7. Influence of pesticides on hatching success of fish.
8. Determination of enzymatic modes of action of pesticides.
9. Pesticide behavior in water, mud, fish-food organisms, and fish.
10. Development of analytical methods for pesticides and associated
industrial pollutants.
The following research highlights on this aspect of the work may serve
as examples to further illustrate the varieties of the research performed:
Guthion and leptophos were the most toxic of a group of 32 pesticides
tested on freshwater fish. A dinitrophenol herbicide, dinoseb, was more toxic
(10-100 ug/1) than most herbicides.
Toxaphene at 10 to 32 ug/1 delayed midge emergence and appeared to
inhibit mating.
Changes in alkalinity of pH 7.5 to 9 increased the toxicity of some
pesticides substantially; for example, zectran toxicity increased 25-fold.
Endothall accumulation was below detectable limits (20 ng/g) in rainbow
trout at 1 or 12 hours after application at practical rates to an artificial stream.
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Hepatic microsomal preparations from channel catfish metabolized
di-n-butyl phthalate to phthalic, palmitic, oleic, and stearlc acids, which were
identified by GO-MS and radiolabeled standards on TLC.
The highest organochlorine residues in eggs from striped bass collected
from females in spawning migration from the East coast were 10-fold those which
have been causing problems in salmon in Sweden.
As mentioned above, some research on non-target species Is being done
at the Great Lakes Fishery Laboratory. Studies here include surveys of mercury,
the DDT complex, dieldrin, and PCB residues in the Lake Michigan fish; a survey
of lead in fish of the Great Lakes; effects of PCB's on uptake and storage of DDT
and DDE from water by the lake trout; baseline measurement of the enzyme
allantoinase in Great Lakes trout; and determination of the subcellular binding
or storage sites of contaminants in the lake trout.
About 10 of the Cooperative Wildlife Research Units and 5 of the
Cooperative Fishery Research Units are evaluating the hazards to fish of
dieldrin, PCB's, DDT, and mercury.
Through the Federal Aid in Wildlife Restoration Act and the Federal
Aid in Fish Restoration Act, certain monies are made available to the states
for related fish and wildlife restoration projects. A number of states have
utilized these funds to conduct pesticide residue surveys or limited research on
pesticides and other pollutants. For example, the California Department of
Fish and Game Is investigating the effects of certain herbicides on a big game
habitat supported by a Federal aid project.
Other agencies of the Department of the Interior that conduct or support
pesticide research include the Bureau of Reclamation, Office of Water Research
and Technology, and the National Park Service.
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Bureau of Reclamation
The Bureau of Reclamation has been involved for some time in research
on pesticides for the control of aquatic and ditchbank weeds and other pests in
irrigation systems. Early studies centered on finding effective methods of
controlling plant pests. New studies are concentrated on obtaining the informa-
tion necessary to register pesticides that are useful and safe. The Bureau is
continuing with research projects aimed at finding better pest control methods
and evaluating habitats produced by irrigation systems.
Bureau of Reclamation projects provide about 20 percent of the irriga-
tion in the Western United States. The pest control methods and the pesticides
developed and registered by Reclamation are used, not only in its own operations,
but by water user organizations that operate many of the Bureau's projects and
also by a number of private irrigation developments.
A considerable amount of information is necessary to register pesticides
for use on irrigation water distribution and drainage systems. Residue data
are needed for drinking water, agricultural crops, and fish and animals that
may drink the water or eat the irrigated crops. Because pesticide uses are in
the minor-use category, Reclamation must underwrite or share the cqst of
registration with other agencies.
The Bureau's main research facilities are located in the Engineering and
Research Center in Denver, Colorado. The center is fully capable of analyzing
for pesticide residues. Research Is conducted in cooperation with the Fish
and Wildlife Service and the Agricultural Research Service.. The Bureau of
Reclamation usually determines residues in water; the Fish Pesticide Research
Laboratory of the Fish and Wildlife Service obtains residues in fish; and the
Agricultural Research Service obtains residues in crops.
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Field studies are conducted on Reclamation projects at various field
locations which allow for collecting samples under varied field conditions.
The Bureau also has limited funds for research through their regional
offices. Studies are being conducted by the University of California at Davis in
cooperation with the Agricultural Research Service and state agencies. One
project is to evaluate the white amur as a method for weed control.
The Bureau of Reclamation is cooperating with the Fish and Wildlife
Service on studies of zinc phosphide for control of meadow mice and ground
squirrels.
Reclamation works closely with agricultural chemical companies to
obtain product registration either by conducting research that yields data that
the companies use for registration or by identifying informational needs relative
to registration.
The Bureau of Reclamation encourages studies through cooperative
agreements with the Environmental Protection Agency and other agencies, because
the registrations they obtain often have utility for many other Federal and non-
Federal agencies.
Office of Water Research and Technology
The Office of Water Research and Technology in the Department of the
Interior supports about 330 contract studies on water quality management and
protection. A number of these involve pesticide and other pollutants in aquatic
environments as related to water quality. The 1973 Water Resource Research
Catalog, volume 8, parts I and n, gives details of these currently supported
research contracts.
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National Park Service
, The National Park Service has a preliminary study dealing with arsenic
accumulation in a species of stone crab, which is being done at the National Park
Service's Science Center located at the NSA/Mississippi Test Facility in
Bay St. Louis, Mississippi.
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FROM INDUSTRIAL R & D TO THE MARKETPLACE
Edwin F. Alder, Ph.D.*
It is a pleasure to be with you this afternoon representing the National
Agricultural Chemicals Association. We are pleased to be able to include the
view of industry in this overview of worldwide pesticide research.
It seems appropriate that this pesticide symposium should be held here in
Denver where the first housewives' supermarket revolt over higher food prices
was staged several months ago — appropriate because our subject, pesticides
and their usage, has been a big factor in helping to keep expenditures for food in the
United States down to a lower percentage of total income than that in any other major
country in the world. But, as Professor Kljajic and others have pointed out today,
the worldwide demand for food is increasing. Even in this country, low food
prices and the luxury of surpluses appear at an end. And it will require the best
scientific efforts of industry, government, and the academic world to meet the
demands of the future.
Research and Development of a Pesticide
The purpose of my discussion today is not to justify pesticide usage, but
to acquaint you with at least a part of the research and development that goes into
a new pesticide, and to identify some of the major problems and issues facing
continued development of new, effective, and environmentally compatible pesti-
cides.
You have heard many times that it now takes $6 to 10 million and
7 to 10 years to find and develop a new pesticide. Let's see just what this
expenditure of time and money gets for us as consumers.
*Vice-President, Lilly Research Laboratories.
225
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The expenditure can best be summarized by the pesticide label. Each
pesticide label gives the chemical name of the pesticide, identities areas of use,
and provides application directions along with certain precautions or restrictions.
Behind the label is a huge research effort that has required the ingenuity and labor
of dozens of scientists, specialized equipment and laboratories, and literally hun-
dreds of tests to prove the efficacy and safety of the chemical in actual usage.
In its most elementary form, the development of a new pesticide can be
said to center on two areas: efficacy and safety. Efficacy data demonstrate that
the pesticide kills certain insects, controls certain plant diseases, or kills certain
weeds. Safety data demonstrate that the pesticide is safe to the applicator, others
exposed to the treatment, consumers of the products, the environment including
wildlife, birds, and fish, and the crop to be treated.
The requirements which may be necessary for registering a new pesticide
result In volumes of data. In the development of our company's major herbicide
product, the research results contained In 110 notebooks have been collected and
submitted to Federal government agencies during the past 11 years. The types of
data that must be developed can be roughly categorized as biological, toxlcologlcal,
environmental, and chemical with considerable overlapping and intermeshlng of these
categories.
Some of the biological parameters are shown In Figure 1. To have a
pesticide, first we have to find biological activity. This we do by screening
chemicals for the desired pesticidal activity. Once that Is in hand we determine
the rate range required for pest control. And we determine the method, the
technique of application — will It be applied to the soil surface, the foliage,
incorporated Into the soil or how? Through further field studies we determine
the spectrum of pest control, crop tolerance, chemical and physical compatibility
of the compound when mixed with other pesticides likely to be used In the same
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application, the half-life in soil and animals, the rate and method of dissipation
in the soil, the duration of biological activity (or the persistence), and the run-off
and leaching characteristics. In addition, in these field studies we observe any
effects on crops that follow in the crop rotation.
Figure 1
Biological
Screen for biological activity:
Insecticide
Fungicide
Herbicide
Growth regulator
Bate range studies for efficacious pest control
Application techniques:
Soil incorporation
Foliar
Soil surface
Determine through field trials:
Spectrum of pest control
Crop tolerance
Compatibility with other pesticides
Half-life
Soil dissipation
Duration of biological activity
Runoff and leaching
Crop rotation practices
Manage experimental permit program
Provide technical service to the user
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As development progresses we establish an experimental permit program
and eventually, after the product is on the market, provide technical service to
the user.
Figure 2 lists the types of toxicological data which may be required for
the establishment of a pesticide tolerance in food crops. The general types of
information are acute toxicity, subacute toxicity, and chronic toxicity along with
special studies.
Figure 2
Toxicological
Acute toxicity:
Oral LD Inhalation LC
Dermal LD Skin irritation
50
Eye irritation
Subacute toxicity:
90-day feeding
21-day dermal
21-day inhalation
Skin sensitization
Chronic toxicity:
Chronic feeding 2-year Including carcinogenic
evaluation
Three generation reproduction
Teratogenic
Mutagenic
Special studies:
Metabolism
Antidote
Neurotoxicity
Gastrointestinal irritation
Lung irritation
Toxicity interaction
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Acute toxlclty studies Include the obtaining of oral and dermal LDso in
mammals as well as eye irritation, inhalation, and skin irritation studies. Sub-
acute toxlclty includes a 90-day feeding study, 21-day dermal, 21-day inhalation,
and skin sensitization. Chronic toxicity studies include the 2-year feeding study
with a carcinogenic evaluation, 3-generation reproduction, teratogenic, and muta-
genlc studies. Special studies may include metabolism studies, search for an
antidote, determination of neurotoxicity, gastrointestinal irritation, lung irrita-
tion, and any toxicity interaction discernible.
Figure 3 depicts the kinds of investigations carried out to determine the
impact of pesticides and their degradation products on the environment. As
previously mentioned, research is required to determine the rate of dissipation
in the soil and the duration of the biological activity. The methods of degradation
(such as decomposition by light and microorganisms or chemical degradation)
are studied. Leaching studies determine Hie amount and rate of movement
downward and laterally through the soil with water. The amount of chemical
removed in surface run-off water must be determined, along with any adverse
effects that the chemical may have. The release of soil-bound material by
subsequently planted crops and the accumulation of the compound or its metabo-
lites In fish, mammals, and birds are studied.
The chemists' contributions are listed in Figure 4. The outline program,
of course, started with chemical synthesis and was followed by the preparation
of related compounds and studies relating to structure and activity, and culminated
in patent applications in various appropriate parts of the world. The chemical-
physical properties had to be established. Analytical procedures had to be
developed to find the chemical in plants, soils, and animals. It is the chemist
we look to to determine the metabolites - the breakdown or decomposition pro-
ducts — and he must determine the rate of breakdown in the soil or in the crop.
The stability of the product in the container must be evaluated to ensure that
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the product remains usable for foe length of time it is likely to remain in storage.
Various chemical manufacturing processes must be studied, with considerable
attention given to the process which uses the least expensive, most readily
available raw materials and which produces the most environmentally compatible
waste streams. The cost of production must be determined and procedures
eventually set up to monitor and maintain control of the quality of the chemical.
Figure 3
Environmental
Bate of dissipation in soil
Mechanicm of degradation:
Photodecomposition in soil and water
Effect on microorganisms
Effect by microorganisms
Degradation in water
Duration of the biological activity
Leaching studies
Runoff studies
Release of soil-bound material by subsequent plants
Accumulation of products in fish, rabbit, and bird
tissue
Only a part of the research required to establish the efficacy and safety
of a pesticide has been shown. New and improved techniques are constantly
being developed and will be used as soon as their dependability and relationship
to the real problems under study are established.
The comment was made yesterday that many of the current pesticides
were registered 10 to 25 years ago when requirements were much less stringent.
This is true, but for many of the major products, new indications of use and new
label claims have, in essence, caused the compound to be reregistered many
times over the years. At each label revision new research information has
been submitted. Thus, we have kept up an ever-improving technology base.
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Figure 4
Chemical
Chemical synthesis
Analog synthesis
Chemical structure-activity studies
Patent preparation and submission
Determine/develop:
Chemical-physical properties
Analytical procedures for plants, soils,
and animals
Biochemistry metabolite research
Decline curves for soil and crop
Different formulations - E. C., W. S.,
W. P. granules
Stability of different formulations
Chemical manufacturing processes
Cost of mar/ifacturing data
Chemical q/ality control measures
Status and Outlook of Pesticic'/j Industry R & D
What is the current st
the health and outlook of the ]
profile study carried out by I'
ducting pesticide research ar
tus of industry research and development effort,
jsticide industry? In 1970, there was an industry
VC. A questionnaire was sent to companies con-
development. Thirty-three of these companies
responded to a private accov/iting firm that assembled the data and attempted to
draw an industry profile. /
A few results from /iat study are shown in Figure 5. The 33 participating
companies reported $69.9 \ illion in pesticide research and development expendi-
tures in 1970 — an increaf / of 33 percent over 1967 expenditures, though much of
this increase was thought / be not research on new compounds but research to
maintain present productf /m the market.
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Figure 5
Pesticide RfcD Expenditures of Participating Companies
1967 1970 % Increase
1967-70
0
R&D Expense 52.4 69.9 33
($ Millions)
Figure 6 gives sonie measures of the time and effort required to develop
pesticides. These figures indicate that the surveyed firms applied 2,768 man-
years to pesticide R&D activities in 1970. One might view this as a measure-
ment that excludes the effects of inflation and simply sums up the human effort
applied.
Figure 6
Measures of R&D Activity in Participating Companies
Man- Years expended
Dollar expenditures
1967
2368
52.4
1970
2768
69.9
% Increase
1967-70
17
33
($Millions)
Another consideration (Figure 7) was the time required from pesticide
discovery to marketing and use. This was growing rapidly. The cost of discovery
and development of a marketable pesticide product was estimated at $5.5 million
in 1970 — up 60 percent from 1967. The combined opinion of surveyed companies
was that about 77 months are required to take a compound from discovery to
marketing _ an Increase of 28 percent in the time required since 1967. We
suspect that these rates of increase since 1970 will prove to be linear.
Another similar study to update me 1970 report has just been carried out
by NAC and will be available this fall. In addition, the EPA has commissioned a
study to attempt to determine the effects of FIFRA amended on industry research
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and development. From these two surveys, we should be able soon to obtain a
more up-to-date picture of the health of industrial research and development of
pesticides.
Figure 7
Industry Estimates of Typical Pesticide Development Requirements
% Increase
1967 1970 1967-70
Cost of discovery and development 3.4 5.5 60
($ Millions)
Elapsed time from discovery to
marketing (Months) 60 77 28
Number of compounds screened 5481 7430 36
for each new product marketed
You have heard from time to time of the companies that have dropped out
of the pesticide business, or dropped segments of R & D activity, or reduced
their overall scale of operations. Various reasons have been given for these
actions, with excessive government regulation one of the more prominently
featured reasons.
However, if you will examine carefully the companies that have gone out
of the pesticide business, you will find that some of them were scarcely ever in
it. They really didn't have the commitment to the kind of research and develop-
ment effort that is required to put a pesticide on the market. Some thought it
was a shortcut to profit and found out to their sorrow that a lot of patient money
is required to develop and market pesticides. Other companies became dis-
couraged when their present major products were in jeopardy for one reason or
another. Or, in still other cases, the pesticide business represented a very
small part of the company's overall business, and the company felt that it was
contributing a bad image to their major activities and therefore elected to drop
out. Whenever there has been substantial new technological activity in an indus-
try — whether it be automobiles, electronics, aircraft, plastics, drugs, or
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whatever — there has been a shakeout of companies. Some shouldn't have been
In the business In the first place, have recognized It, and have left. Others have
fallen behind and withdrawn. Others have merged or sold out and disappeared
from the scene. This Is certainly not an abnormal situation or necessarily an
unhealthy one. The pesticide industry Is no different in this respect from other
high technology Industries. We'll have some Nashes, Hudsons, and Packards
and even a few Edsels in the pesticide business.
But, as some of the companies have gone out of pesticide research In this
country, other foreign companies have come in. We now have an array of German,
Swiss, British, and probably eventually Japanese activities filling the gaps. We
have not seen any lessening in competition in this business. The state of compe-
tition in pesticide research and development remains quite healthy.
Future of Pesticide Industry R & D
As to the future, up until now some of us have viewed the situation
rather philosophically and simplistically and made some basic assumptions:
That people are going to have to eat; to eat we are going to have to grow more
food for more people; we are going to have to control pests; and the bulk of pest
control must be done by the use of pesticides. To have pesticides we must
have research. We must have research to maintain present pesticides on the
market and to introduce new and better materials to control resistant pests or
newly introduced pests around the world or to improve on the safety or environ-
mental properties of older, less desirable products.
As agriculture has grown and continues to grow increasingly Important
in this country (as It has in the past 2 years when countless millions learned for
the first time that groceries don't arise de novo in the grocery store) we have
assumed that all inputs for agriculture will likewise become more important and
that there is a place for industry in producing pesticides and in doing research to
bring new products on the market and that this will continue to be the situation
for many years to come.
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We In industry are not pessimistic about the future of agriculture, the
need for new technology in agriculture, or the contributions we can make to
agriculture, to the welfare of our country, and to the welfare of mankind. We
have felt that, over the long run, we are in a growth industry, one that is limited
only by our own innovative capabilities.
Pesticide Industry Concerns
So what are our problems? What are we concerned about? We have a
number of concerns, some growing and others diminishing in importance.
Perhaps the most serious threat to pesticide research over the past 2
decades may very well be certain new regulations now being promulgated. Some
of us had rattier naively thought that any regulatory hurdle put in our path could
be overcome by research -- that as long as regulations were administered fairly,
we could survive. Now we are not that convinced, primarily because our
capability to do research is being challenged as never before.
A specific grave concern, which is now fading, was the proposed regula-
tions on experimental use permits. These regulations as they were initially
proposed would have unquestionably curtailed our research effort, caused our
efficiency to decline, greatly increased the cost of doing research, and
lengthened the time for any payoff on research investment. If these regulations
had not been substantially modified, our research costs would have increased;
research would have, in part, been encouraged to move out of the country; costs
of pest control would have increased; and American agriculture and eventually
the consumer would have been the poorer for it. We are pleased to report that
the new draft of the regulations appears much more acceptable and we would urge
its adoption.
Another concern is the recurring notion that the government or some
"independent" contractor can do the job of researching and registering pesticides
better, or at least more honestly, than private industry. I would submit that no
individual really familiar with industrial research would challenge the integrity
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of the industrial scientists. I am proud of the integrity and responsibility shown
by the scientists in my company and in the companies with which we compete. We
as scientists are well aware that our data must be honest and must be scientifically
sound. Our work must stand up in the scientific community as well as withstand
the scrutiny of regulatory agencies, and It must stand the ultimate scrutiny* the
crucible of the marketplace. Remember that Industry scientists have received
•
the same basic training as "Independent" scientists, schooled In the same scientific
philosophy and Integrity, under the guidance of the same academic scientists.
We didn't lose the principles Instilled by such training just because we went to
work for Industry. Moreover, because of our motivation, we in the private
sector feel we can discover and develop pesticides more efficiently than any other
sector.
We have frequently hrard that Incentives should be offered to industry to
develop new and better pesticides. What Is Industry's feeling on Incentives?
Frankly, some of us run for shelter or look for the nearest exit when any
government group mentions providing incentives for us. By the time the
"Incentives" are brought forth, they usually turn into dis-incentives.
A good example of this is the compensation for use of data provision of
FIFRA amended. This provision was, we are sure, intended to be an incentive for
Industry. It is proving to be a headache to many of us in industry as well as in
government. For the record, we are, nevertheless, hopeful that the final regula-
tions will prove equitable and workable.
As a genuine incentive we have constantly pleaded for faster reaction to
registrations. We are confident that important steps are being made in this
direction. Recent reorganization of the Pesticides Registration Division to
institute a product manager system is indicative of EPA's interest in increasing
efficiency in the registration process. We are hopeful that these product managers
can work effectively between industry regulatory representatives and EPA review-
ers to decrease the time required to get registrations.
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We are always concerned in any review that recognition should be made
that each individual use of each compound must be considered separately.
Blanket condemnations and categorizations of compounds are not good science or
good economics and are very poor politics. Persistence per se should not be
equated with evil. Some compounds need to be persistent to be effective. Only
by looking at each intended use of each compound along with its chemical and
biological characteristics can sound judgments be made.
Another concern of industry is government grants for research studies.
The unknown is always feared. When research grants on our established products
are let and we read about them in the "Commerce Business Daily*" we are
naturally fearful. Why is this study being run? Were our submitted data inade-
quate? Are the contractors really familiar with the analytical or other techniques
that we have struggled wil-h for years? Does EPA know we have data on file that
answer these questions ? Why didn't they tell us ? How can we find out what's
going on? We would earnestly plead to be dealt in on the action. If there are
questions, let us present the information we have. Perhaps data have been lost
or misplaced. Any information EPA can provide us on the reasons for letting
a grant will be most welcome. If a compound is not really suspect, any
reassurance that can be offered will serve to strengthen our confidence in the
regulatory process and to dispel our fears that some precipitous action is under
way. Our request for more information is, we recognize, difficult to consis-
tently put into practice. It would, however, appear to be in accord with the
policy of openness in EPA which was expressed and reiterated yesterday.
Positive Aspects, Present and Potential
Well, what's going right? Actually, many of the concerns I have men-
tioned are diminishing as later draft regulations are forthcoming and better
communications and mutual trust are established. Other positive things are
happening.
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The efforts of the Criteria and Evaluation Division of EPA to initiate
studies through grants programs to develop new methodology to deal more
effectively with the "genesis" questions are laudable. We urgently need new
test methods to measure carcinogenic, teratogenic, and mutagenic potential. If
we could determine which compounds will likely present problems, we could
abandon them before we invest heavily in them, and we could then devote our
resources to safer compounds and greatly improve our efficiency.
We would further plead that for genesis evaluations to be really meaning-
ful they must relate to the use levels of the pesticide. We must get some concept
of dosage response into these evaluations. Long-term dosage of high levels of
pesticides to test animals does not represent actual exposure conditions in the
environment or necessarily yield useful data. Such evaluations work to the
severe disadvantage of compounds having low acute toxicities, when they are
tested at unrealistically high levels simply because long-term high dosage studies are
possible. As Dr. Coulston pointed out this morning, any time that we exceed the
capacity of the test animal to metabolize a compound in a long-term study we are
likely to encounter liver tumors late in its life cycle. Paradoxically, chemicals
that are highly toxic in single doses and potentially more hazardous to the
applicator may come into greater use because the acute risk, even though high,
can be measured and the long-term risk cannot. We would, therefore, make the
plea that the "maximum tolerated dose'1 be replaced by a dose level arrived at by
careful consideration of the test animal's metabolic capacity and the potential
residues.
A cooperative field tour training program is now being established. This
i
program, which has been enthusiastically supported by industry and EPA, is to
permit field tour training in industrial settings for individuals in EPA who review
applications for registration and who draft regulations and guidelines, and for other
key personnel. This will better acquaint them with techniques and programs used
by industry in the development of new pesticides and perhaps instill greater confid-
ence in the quality of industrial research. We are optimistic that it will provide
a greater understanding and appreciation of the roles of both industry and EPA.
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There has been considerable discussion in EPA and elsewhere about the
development of new pesticides and the maintenance of current pesticides cleared
for minor crops or for minor uses. Increased requirements for registration and
Increased costs of doing pesticide research threaten the continued flow of new,
safe, more effective pesticides for use on minor crops. We are pleased that a
temporary coordinator for minor-use pesticides has been appointed. We suggest
the following ways that industry can be encouraged to work on minor crops:
• Establish crop tolerances by commodity grouping.
• To avoid seizure liabilities, set tolerances for minor crops at
lexicologically safe levels rather than the maximum encountered
in tests.
• Accept data on performance and residues from selected major crops
to represent minor crops insofar as possible.
We realize that some aspects of these suggestions may require new law or new
regulations, but with these approaches we think the minor-crop problem could
be alleviated.
With some trepidation I will venture Into a controversial area to offer a
hopefully positive suggestion. Criticism is frequently directed to the selection
of test animals for extensive long-term studies and the subsequent extrapolation
of the animal data back to man. To help answer this criticism we suggest that
more frequent use be made of limited studies In human volunteers. Such investi-
gations, which are already commonly carried out In pharmaceutical research and
occasionally In pesticide research, elucidate the metabolism of a compound
administered to man. Human metabolic pathways can then be compared with
those of various animal species. A matching animal pathway will permit exten-
sive Investigation In that species and should correlate better with the events which
occur In man. We would echo Dr. Coulston's general admonition, however: Please,
no guidelines on this! At this time encourage It only and let us as individual com-
panies pursue this approach as we can.
The fact that we are having this symposium is, we feel, a healthy sign
and a positive action which we commend. Certainly the meetings that Drs.
Axelrod, Korp, and Buckley have held with the Research Directors Committee of
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NAC have been helpful and informative. Dr. Axelrod has patiently met with our
committee on several occasions, has taken our views and concerns on the
Alternative Chemicals Program into account, and has made a sincere effort to
keep us informed. The mutual understanding eventually developed is an example
of what can be done by cooperative endeavor and perseverance. Please keep up
this activity. Don't quit talking to us even if we disagree now and then.
Summary
In summary, we in industry feel pesticides are and will be essential to
food production and human health. We feel that the vast amount of work
presently being done on new pesticides does establish safety and efficacy. We
are attempting to monitor the pulse of the pesticide industry and feel that it is
still healthy. Additional information will be forthcoming soon.
We are concerned about various regulations being promulgated but are
encouraged by more recent drafts of some of these regulations. We reject
totally any accusation that industrial scientists lack integrity or objectivity. As
incentives we only ask that the regulatory system work as efficiently as possible
and that in any review of registered products, each use be looked at individually.
We urge that communications be strengthened to let us know if the safety or
efficacy of one of our pesticides is being questioned. We would greatly appreciate
help in developing reliable tests on genesis problems and urge that long-term
feeding studies be at realistic dosages that do not exceed the metabolic capability
of the test animals.
We are pleased that the cooperative field tour training program is getting
under way. We suggest some modification of requirements for minor crops. We
suggest that greater use of human volunteer studies would prove useful to compare
metabolic pathways prior to chronic toxicity studies; and we urge that all
communication lines among EPA, the academla world, and Industry be main-
tained and nurtured.
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RESEARCH AND SPECIAL CONSIDERATIONS:
NONAGRICULTURAL USE PESTICIDES
Mr. Melvln Garbett*
The homeowner, like the farmer, is faced with the problems of pest. But
unlike the farmer, the homeowner in most cases cannot identify his problems
and in most cases doesn't get the expert advice to give him the help he needs.
To most homeowners the whole concept of agriculture is a potted geranium. They
don't have the knowledge of a specific crop and the specific problems that can
occur. It's not a matter of "How do I control cabbage looper in my soybean field,"
but rather "My roses don't look so good, what can I do about it?" You ask, "What's
wrong with them?" "I don't know — something's been chewing at the leaves. " The
sales clerk at K-Mart may or may not be of help. And by the way, this is who
they often rely on for their help. Somebody has to provide solutions to their prob-
lems. State extension experts don't make house calls and we don't have enough
local clinics to prescribe solutions to their specific problems. So what's being
done to solve the homeowner's problems? Is industry participating? You bet it
is!
We have taken on that responsibility. However, specific recommendations
for specific problems are not the solution. The answer must be to provide pro-
ducts that do many jobs, offer broad-spectrum control with well defined, easy-to-
follow label directions. We have to make it easy, not only for the user, but also
for the person selling. Do you begin to see what we're up against? This is a
very unique area in pesticide development.
As the homeowner's problems differ from the farmer's, our research
efforts differ from those of agriculture. I'm not talking about spraying several
acres of cotton or soybeans, but a few square feet of lawn. I'm not talking about
aerial applications or row crop sprayers, but aerosol cans and 1-gallon Hudson
sprayers. I'm not talking about producing 100 bushels per acre, bat producing an
*Supervisor for the Garden and Home Research Department, Ortho Division,
Chevron Chemical Company
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environment of beauty. It Is a different ballgame and a ballgame requiring a
different set of rules — or another way of putting it — requiring special considera-
tions.
The way I see it, the EPA rules and regulations are designed to do one
thing: to prevent unreasonable adverse effects to man and the environment. As
a member of industry and a private citizen, I can say that we support that 100 per-
cent.
This support is reflected in our research efforts. Over the past several
years we have identified and developed solutions to the problems facing the home-
owner. As we put together products we are acting from a basis of knowledge, not
solely on the basis of the almighty dollar. G&H pesticides are not arbitrarily put
together. At Chevron, for example, we have a team of experts and experiment
station facilities throughout the country continuously developing new and safer
compounds, testing under controlled conditions, demonstrating under typical use
situations, continuously Improving products and making sure products continue to
do the job they were designed to do. Can the effective dosage be reduced? Can
we Improve on the solvent system? And Indeed, are they environmentally sound?
There's much work to be done on the older compounds and their effect on
the environment. It's agreed they need to be updated, but within a reasonable time
table. Let's not just simply discard them while determining their Impact. There
aren't really that many compounds available to the homeowner as It Is. The supply
has been greatly trimmed over the past few years.
Where are we heading? I hear stories about pest resistant varieties,
possibly In the role of plant disease control. Cultural control ? Biological con-
trol ? Perhaps. But they have their limits as you well know. Bacillus thurln-
glensls gives control of certain lepldopterous larvae, but how do you tell a home-
owner to apply between second and third larval Instar ? And some pests have few if
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any natural enemies, or those enemies do not act in time to prevent serious
plant damage. Integrated control makes more sense — to include chemicals
when needed but to use them sparingly and judiciously. The homeowner may never
have heard the term "Integrated Control." He's not aware of it, but he i£ using it.
He uses the pluck and squash method when he sees a caterpillar and sprays when
he sees numerous caterpillars or extensive damage. He's not on a spray schedule
like the farmer. The homeowner sprays intermittently, when needed, in small
amounts — in most cases no more than 3 to 5 gallons of diluted spray per applica-
tion and usually less. This again reenforces the fact that this is a different
business from that of commercial agriculture.
Another responsibility taken on by industry is to help the homeowner make
better use of the pesticides available to him. I can give you several examples:
• Easier to read and understand label directions
• Accurate applicators with automatic dilution ratios
• Pre-measured pesticides
Industry has the manpower and technology to provide better use of what we
have. And we must continue to use it.
At the same time we must utilize our manpower and technology in develop-
ing new compounds and products for garden and home use. Do I have to bring up
the tremendous pressures put on us by EPA to meet the requirements to register
new compounds ? An experimental permit to spray a rose bush! Data on Eastern
tent caterpillar must be separated from that of the Forest tent caterpillar and each
must be labeled separately! Approximately 50 percent of the label is taken up by
cautions and warnings, leaving only a small portion to label use directions, pests,
and hosts! Moreover, we're told that we can't recommend a particular product
for a use not on the label, regardless of whether It's registered or not for that use!
Don't get me wrong, cautions and warnings are Important, but do we need to label
our Sod Webworm Control with "This product is toxic to shrimp and crab" ?
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The enormous amounts of money and time required to meet these demands
go without mention. You've heard It over and over again, but it does lead to a
very Important point. As there's a risk-benefit factor in the use of pesticides,
there's also a risk-benefit factor in corporate decisions. Not too long ago, the
Vice-President of Ortho asked me a simple question: "Should we be in the G&H
pesticide industry 8 to 10 years from now or should we be looking into other ventures?"
Well, the idea that something like this entered his mind scared the heck out of me.
But risks such as product cancellation, alternate chemicals, relabeling problems,
and inventories are nothing but headaches to corporate management. With the
increased pressures from regulating agencies on our business, will management
continue to appropriate funds for research and development, expansion, facilities,
people, etc. ? Will they continue to support research and development for minor
crop uses with the risk being greater than the benefit? As I've already established,
it is a risky business. How much will corporate management take?
While millions of dollars are being sunk in a relatively high-risk venture,
the same dollars can often more safely be invested in the corporate stock or a less
risky endeavor such as the panty hose business. Over the past few years we have
seen several large corporations make the decision to "get out of the G&H pesticide
development business. Increased pressure on industry could cause additional com-
panies to make that same decision. Inevitably having an effect on those companies
surviving the pressures, It will lead to discouragement and a reduction In research
for new, better, safer chemicals which will meet the rigid standards required In
protecting the environment. What Is needed more than ever are Incentives. You've
got to give them to us. Incentives that will encourage research not discourage It.
In summary, I would like to briefly reemphaslze the four major points I
have covered here today.
1. We must recognize the fact that the use and development of garden and
home pesticides are greatly different from those of commercial agriculture.
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2. Industry can supply the manpower, facilities, and technology to
locate and solve the problems of minor crops, and we must continue to do so.
3. New and safer pesticides are needed for the future, and incentives
need to be provided to ensure they will be there.
4. And most important, let's be sure to protect the old while developing
the new.
MS. ROSMARIE VON RUMKER: I wonder if you could be a little more
specific on what incentives you would desire and how and by whom they should be
provided.
MR. MELVIN GARBETT: By incentives I guess I really mean encourage-
ment.
MS. VON RUMKER: Encouragement from whom — from the consumers
or from the governments or ...
MR. GARBETT: No, from the regulating agencies of EPA.
* •
MS. VON RUMKER: Well, by words or by what? How should . . .
MR. GARBETT: Okay, here's an example. For instance, we want to
provide the homeowner with easy-to-read and easy-to-follow label directions.
Presently when we label a product we have to label a specific insect for a specific
plant, such as aphid on rose. Now to do that with every insect on every plant
that we would like labeled, we would have to include an encyclopedia with the
product.
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So what I have proposed is that we can list in one column the insects where
we have efficacy data, and in then another column we can list the plants that are
attacked and where we have phytotoxicity data, rather than a particular insect
for a particular plant. As far as I'm concerned, and I think I can speak for the
CSMA, the ultimate label for garden and home use, is that "This product controls
Insects on your plants." We'll never achieve that, but it's a goal. This is the
sort of thing I'm talking about when I say "incentives" — an easing in regulations
that will encourage further development of garden and home pesticides.
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THE FUTURE OF PESTICIDE RESEARCH: A CHALLENGE
Leonard R. Axelrod, Ph. D. *
International research considerations began with discussions by Dr. Lu
and Dr. Turtle, and a broad spectrum of academia and government was brought
into play; Dr. Alder brought in tibe myriad of research needs of industry, not
only to comply with government regulations but also to contribute to the develop-
ment of new pesticides.
I should like to discuss the world of pesticide research, which to me is
an exceptional challenge, and I think I have the naivete of a newcomer to be able
to think in a rather broad spectrum of possibilities. I hope that when I'm finished,
you will be able to walk out and say to yourself, "Why that was perfectly
obvious." That would mean that we are thinking innovatively of the possibilities
for the future.
The introduction of biologically derived materials for the control of pests,
such as viruses, bacteria, juvenile hormones, growth hormones, pheromones,
parasites, and predators, represents the "new generation pesticides." For
these materials, "tomorrow is already here." Thousands of man-years have
been devoted to research on the development, synthesis, safety, and efficacy of
most of these instruments of control. Inevitably, many, if not most, will be
registered and incorporated into the arsenal of those who labor for the protection
and production of our food and feed, the agricultural community.
Today, however, I would like to go somewhat beyond the many so-called
"new generation pesticides." Today, I would like to voice some lateral thoughts
in an abbreviated synopsis primarily to provoke thoughts and discussion, because
"tomorrow is already here" in the need for innovative and lateral thoughts in the
field of pesticides.
*Dlrector, Criteria and Evaluation Division, Office of Pesticide Programs, U.S.
Environmental Protection Agency
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The fervent hope is that all concepts are "perfectly obvious" and that the
future of pesticides can be anticipated. Pesticides, however, are only part of the
story. An overall look at our civilization must be taken first to discern just
where pesticides fit Into the picture. The future of our society will be shaped by
many things.
It will be shaped by many different technologies which break down simul-
taneously; it will be shaped by many crises which will occur and which may be of
magnitude greater than that which has been coped with in the past.
It will be shaped by the fact that pollution and technology tend to grow
exponentially and in parallel, so mat critical problems and subsequent damage
may occur before cognizance of such damage is anticipated and is prevented.
It will be shaped by the interpretation of human values in our culture, the
unifying concern for long-term human survival.
It will be shaped by physical operational parameters for our planet, that
is, the ecological or housekeeping rules that govern human occupancy.
It will be shaped by the contextural interplay of fear, affluence, standards
of living, and population among our societies and nations.
It will be shaped by our evaluation of priorities in the utilization of energy,
human and physical.
It will be shaped by the availability and distribution of agricultural products.
It is the last point that is the primary focus of this discussion. Although
all the others impact directly upon how the goals are achieved and the priorities
assessed, it is my considered opinion that the field of pesticides as applied inter-
nationally must depend on a multlfaceted approach, innovatively, to the subject
of pest control, and that this approach must include new broad-spectrum fundamen-
tal scientific research in order to cope with the insects and plants that have
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genetically "tuned for survival" for more than a billion years; and I might say
that the rodents, which have not been here as long, have also contributed greatly
to the destruction of our food and feed.
Unfortunately, it is now the ebbtide of technology in areas of agriculture.
It was the years of 1940 through 1960 and the years at the turn of the century
which gave great advantage to the emerging agricultural community; from the
harvester machines and other mechanically complex systems to the serendipic
discovery of chemicals like DDT, the "panacea" of the agricultural world at one
time, as penicillin was to the pharmaceutical world.
Corn production has risen from 26 bushels per acre to 91, (somewhat
less — 76 — this year). Nevertheless, you can only produce so many bushels per
acre with our present technology. The bugs, the weeds, and the rodents control
20 to 25 percent of our produce.
It is time to look ahead on a broad-spectrum analysis which will require
human resources, funds, and above all, the capacity to think.
The following are some avenues of pesticide research for pest management
and are presented for your consideration and thought.
The insect has been here at least one billion years. The plants (algae),
interestingly enough, have been shown recently to have been here three and one-
half billion years. Their capabilities at a molecular level to survive and adapt
are legion. DDT was introduced about 1944 and this morning my colleague, Dr.
Fred Whittemore , tells me that by 1948 the housefly was resistant. As DDT was
used, it became obvious that more and more was necessary to control the pests
and that finally the resistance was at a point where it was neither economically
nor environmentally feasible to continue.
I submit the following:
1. The introduction of extremely toxic pesticides — pesticides that make
TEPP look toxicologically like jello. In the same package, however, the internal
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controls will be present simultaneously, perhaps by utilization of methods such as
microencapsulation and time-release systems for nullifying (detoxifying and
inactivating chemically) the hazardous effect of the active ingredient.
Footnote for the manufacturers: Please don't throw out the compounds
you don't have on the shelves.
2. Much has been said about the contamination of our soils, air, and
water with pesticides that have been applied unjudiciously in the hopes of a better
agricultural return. It is time to think about the development of chemicals and
techniques to inactivate the hazardous effects of pesticides already on the land-
scape and in the air and water — a definite public health mission.
3. It is time to consider the rhythms and cycles of the insects and plants
the circadian rhythms, the time clocks — diurnal, nocturnal, and crepuscular.
It is time to consider the reproductive cycles of insects, which are controlled
by time, weather, temperatures, and chemicals.
I suggest alteration in specific food selectivity by changing the plant (host)
metabolism, that is, the relationship between the almost parasitic dependence of
an insect species upon its selected food composition, including smell, taste, color,
and pH. If the insect wakes up at the wrong time, before the food is ready or
after the food composition has changed (e. g., sugar to starch) which represents
to the insect that special taste, smell, color, or pH, you have disrupted the
parasitic-host cycle relationship and that is a method of control. It is not an
accident that tomatoes are not attacked by the Japanese beetle but other plants
next to them are. It's also not an accident that plant leaves in the garden are
burned just by proximity to certain other plants in the vicinity.
5. On the other hand, the alteration of the insect's color and smell to
attract predators can also be utilized.
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0. I suggest the development of plant strains of nutritive value that thrive
upon presently considered air, soil, and water pollutants. We had an excellent
exposition by Dr. Kearny who discussed changing plant species for resistance to
insects. The metabolism of plants can also be altered to accept, as part of their
nutrition, such pollutants. We know about sulphur bacteria. In my own laboratory,
we had mold growing in pure sulphuric acid. It did not change the nutrient value
of that mold as far as its protein went. We examined it just out of curiosity one
day about 18 years ago.
Therefore, seek to clean the environment by the use of plants and animal
species that act as sumps for the pollutants and by the use of microbial and sub-
microbial evolved species to harvest these pollutants out of the fresh waters and
even out of the ocean. After all, there is no greater chemist or adsorbant than
life. There is no greater adapter than the genetic code. Use these changes to
destroy the pollutants by harvesting animal and plant life adjusted to thrive on
these pollutants.
7. Develop equational precepts that relate optimal energy expenditures to
crop growth and uses and to food chain goals. I think the economists might have
a place here, as well as the physical and biochemical scientists.
8. Perhaps what may also be necessary is the alteration of national
palates for nutrition rather than mere taste (e. g., "good" instead of "prime"
beef). This could require a reassessment of priority needs in our affluent
societies.
It is time for innovative thinking and discovery. It is time for young and
audacious minds to enter the field of pesticide research.
There are at present fine scientists and innovators in pesticide research,
but they are taken up by the innovations of yesterday and the pragmatism of today.
We need new people, products of the heritage of agricultural communities and
pesticide research, who will enter into mis fracas, into the challenge of pesticide
research.
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We cannot seek a panacea. There is no magic compound. Penicillin was
not magic and neither was DDT. They existed in a moment in time and all but
disappeared. We will not be able to use exclusively juvenile hormones or phero-
mones or viruses on 78,000,000 acres of corn or 17,000,000 acres of cotton.
The problems need broad-spectrum thinking and integration of thoughts, one with
the other, in the areas we've delineated and in many more, which I'm sure that
you've thought about. But the time to begin is now; it's really yesterday for
starting the process.
The discoveries of the 15th and 16th centuries were placed literally into
orbit by our space program. The equations developed for space were not by com-
puters, they were by thinking men in those earlier centuries. Even Dr. Einstein's
hypothesis of mass and energy published in 1905 was not proven until 1919. He
was lucky; that's a relatively few years in science for going from the "drawing
board" to the "proof and the pragmatic application of atomic energy today.
We are as someone in outer space — looking back; you see many problems
but they appear miniature, because none of us can see the particulars of the
whole or what the future will bring. The ideas you put forth today which will be
considered for life on this planet will also alter our ideas of how to deal with
these pesticide problems.
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PESTICIDES RESEARCH
IN THE ENVIRONMENTAL PROTECTION AGENCY:
INTRODUCTION
John L. Buckley, Ph. D. *
I'd like to welcome you to the last of our sessions here. What I want to
say at the outset is that we in EPA in the research area are kind of a diverse group.
We came from various places when EPA was formed, and we've had various
perspectives and various ways of doing business based on the different sections
of the government that we had been associated with. I don't want to make a long
history of this, but I do want to call your attention to the fact that one of the units
brought into the EPA was a single unit out of the Bureau of Commercial Fisheries
in the Department of the Interior All the rest of that Bureau went to the Department
of Commerce, but Tom Duke in Gulf Breeze, Florida came to EPA. The Federal
Water Quality Administration (FWQA) in the Department of the Interior also came
to EPA.
FWQA had a number of laboratories working on water pollution, and
among the substances that they dealt with were a number of pesticides. I would
like the record to clearly show that we don't look on pesticides in any general sense
in EPA as being pollutants, but when in fact they're in the wrong place or when in
fact the manufacturer's waste enters the environment, the pesticides like other
biologically active materials are pollutants.
The laboratories in EPA that came from FWQA that were associated in
some fashion or other with pesticides were the National Water Quality Laboratory
in Duluth, Minnesota, the Marine Water Quality Laboratory in Narraganset, Rhode
Island, and our Southeast laboratory in Athens, Georgia. The Athens laboratory
*Acting Deputy Administrator for Program Integration, U. S. Environmental
Protection Agency
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has continued, as has the Duluth laboratory, to deal in some fashion or other with
research on pesticides. The Athens laboratory has been working in terms of
measurement of methodology and in terms of fate of substances in the environment.
The laboratory in Duluth has been concerned with the effects of pesticides — the
acute and chronic toxicities to fish and other aquatic organisms for many years.
The laboratory in Cincinnati, which also came from that group, has been involved
in surveys of the presence of pesticides in water.
Another large unit concerned with pesticides research that came to EPA
was the group from the Food and Drug Administration. That included the Perrine
Laboratory, the Chamblee Laboratory, and the Wenatchee Field Station.
In addition to these rather discreet units, there were some others which
impinged in one way or another and are sometimes forgotten. The National Center
for Toxicological Research was invented, if you will, by the Secretary's Commission
on Pesticides, which was chaired by Emil Mrak. When EPA was formed the
Executive Branch concluded that It would be well for that concept to go forward, but
for the funding and support of Its programs to be the joint responsibility of EPA
and the Food and Drug Administration. So in the first year FDA was given the
responsibility and EPA was given the money that was set aside for this. This
arrangement led to real close cooperation In the first year. FDA had the manage-
ment and the laboratories but they didn't have the funds. So we did have a consider-
able Influence from EPA on the structure, the Initial thoughts, the management
systems, and the other things which went Into this.
Another unit which was transferred was the Secretary1 s Advisory Committee
on Pesticides, and Emll Mrak and those people who were on the Commission at
that point In time were moved to EPA and became responsible to the EPA Adminis-
trator as an advisory group. This group was renamed the Hazardous Materials
Advisory Committee. Other groups transferred to EPA Included the staff for that
committee, as well as the staff for the Federal Committee on Pest Control.
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The point behind all this information is really that because of these diverse
origins, there were, in fact, various points of view. I wouldn't want you to think
that we all sit here today with an absolutely uniform view of things, but we see
more uniformly now than we did in the past the goals and objectives and the ways in'
which to achieve them.
In addition, I would also like to point out in this introduction that in
regard to research directions, it is our view that the development and/or the evalua-
tion of new and better methods of evaluating safety in all its aspects is perhaps our
major responsibility.
We think and the law clearly specifies that the major responsibility for the
provision of data rests with industry, and in no way do we wish to take on that
responsibility. On the other hana, we do feel a deep responsibility to improve the
ways in which data can be generated and the means by which data can be synthesized
and evaluated. We've been working on this in a number of ways.
The second responsibility we have, it seems to me, is to produce data
needed for understanding of a problem when such data are not otherwise available.
There are a number of situations in which this is clearly the case. For
example, in analytical chemistry there are times we wish to look for a number of
substances in foods or in other substrates. The substances are clearly not the
responsibility of any one industry, and we find it advantageous to develop methods
for these. There are compounds on which information is desired, the patent period
has run out, and there is no proprietary interest. It would be nice if there was
somebody we could turn to for that additional information, but there are cases in
which this is not so, and you know them better than I.
We have a small program that is concerned with what we call alternative
methods of pest control, which I mentioned the other day. Of approximately $8
million in research, including the monies that we're responsible for under the
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Alternative Chemicals Programs, approximately $1.8 million goes Into this
matter of development of alternative methods of pest control. A large part of
that has been for the support for the so-called Hufaker Project — a large number
of universities and Investigators working on non-chemical control methods and
Integrated methods in a number of crops.
We have been In one way or another in the pesticide research business for
quite a number of years. The funds associated with the Alternative Chemicals Program
have somewhat narrower and more specific objectives than the other funds that
we have used and are using. They are not a dominant part of our program in terms
of total monies available. They are, in fact, an important part of our program,
and we hope to work very closely with you in the expenditure of these monies in the
sense of not duplicating what's already done. We may have occasion to validate
data. We may have occasion to do some things that you believe are already done.
However, we have no desire to generate data that you already have.
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OVERVIEW OF ECOLOGICAL EFFECTS
Norman Glass, Ph.D.*
Let me begin by saying that this program is relatively new. In fact it
has only recently begun in the last 2 or 3 months. We received our initial funding
in May or June of this year, and I should point out for those of you who haven't
already read it in the program, that we'll be dealing with the ecological effects
aspects of the Substitute Chemicals Program.
The ecological aspects of this program have been developed on the
basis of the historical and resident expertise at a number of the research labora-
tories from the National Environmental Research Center in Corvallis. In fact,
four of the laboratories represent this center on the Substitute Chemicals Program,
and I would like now to introduce the panelists and identify which laboratories
they're with and what their general areas of responsibility are.
The four laboratories are represented first by Dr. Jim Gillett, whose
detailed biographical material is in your program. Dr. Gillett is from the
National Ecological Research Laboratory. He is basically a biochemist who
has been involved in pesticide research for many years. He's also responsible
for putting together the terrestrial aspects of the program.
Next to him is Dr. Thomas Duke, the Director of the Gulf Breeze
Environmental Research Laboratory in Gulf Breeze, Florida, whose responsibility
is in the estuarine and the marine effects area.
Next to him is Mr. John Eaton from the National Water Quality
Laboratory whose responsibility is in fresh water toxicity or toxicological data
development in the fresh water environment.
Mr. Jim Hill, from the Southeast Environmental Research Laboratory
in Athens, Georgia, is responsible for discussing the fresh water transport of
pesticides.
*Director, National Ecological Research Laboratory, U. S. Environmental Protec-
tion Agency
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My function in this is largely to oversee the ecological effects area and
to try to minimize the number of gaping.holes in our knowledge that crop up in
that area.
Having briefly introduced each of the panelists, let me give you a
quick rundown on the nature of this program as we have seen it. First, as I
mentioned, the program has just begun, but it has two distinct but very related
parts. The first consists of a conceptual framework or a planning document
which describes the way in which all of the various pieces of the program fit
together. This basically could be called a conceptual model, although I would
really like to minimize the model aspect in favor of emphasizing the thought or
the framework within which we can all perform a research program.
The second major portion of the program is a methods development
phase which involves the use and development of microcosms as testing methods
or as testing procedures for evaluating or assessing either new or existing
pesticides.
In our overall compartmental type model, there are several general
categories we will be working in. These include the atmosphere, the
land, fresh water, estuarine waters and marine waters, and the sediments and
other terrestrial components of each of those compartments. Within each of
these categories there is a further breakdown into what we consider most
important, namely the biota which exist in each of those compartments and
the various feedbacks and transports and directional flows of material through
the compartments and among the biota.
Our conceptual framework is in the nature of a compartmental model
which we can break down into program bites, so to speak, which each laboratory
is then free to deal with as an integrated problem. We then integrate the entire
problem into a holistic view of the way in which pesticides move through the
environment and possibly what some of their effects are.
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Now, as most of you probably know, the microcosm methodology which
we are developing is a relatively new type of research and I'd like to emphasize
at this point that even if it were not new and even if it were completely developed,
tested, and validated, it would still not represent the ultimate in screening
procedures or assessment methods which would be used in the registration
process to evaluate a pesticide.
This is only one piece of data which has to go into pesticide evaluation.
Microcosms also offer the advantage of being relatively inexpensive, rapid,
possibly turn-key testing methods as the years unfold and the methods become
better developed, but I would like to emphasize that they are at this tlmfe
extremely rudimentary and clearly in a developmental phase.
In closing, the substitute chemicals which we are investigating under
this program obviously exhibit or may exhibit many properties that are quite
similar to conventional pesticides or, let's say, more thoroughly understood
pesticides. They have properties such as bioconcentration, biomagniflcation,
biological transport through food chains, and biodegradation. It is because
of the presence of and the need to study the many environmental routes, rates,
sinks, and effects of a variety of substances proposed as substitutes for banned
or dereglstered pesticides that we have developed this program.
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TERRESTRIAL EFFECTS
James Gillett, Ph.D. *
We have two basic aspects along which we are proceeding as Dr. Glass
has stated. First, we have been concentrating on the development of the conceptual
model of the interrelationships of terrestrial systems to aquatic systems, and
second, we have been developing methods or approaches using terrestrial micro-
cosms. We have not proceeded very far on the second, because we are a very new
program. We are just moving into new laboratories that will be functioning by the
middle of September or maybe early October.
Then we will move into trying to develop chambers which we can character-
ize — which we can develop as an array of biological and physical conditions or com-
ponents that will represent conceptually, in a way, an organism that is a little
more complex in some regards than a given species, but not as complex as an
actual ecosystem. I refer to these as microcosms and not as model ecosystems,
because they are totally dependent on our Input, our characterization, and our
design. We believe that in a few months, to hopefully not more than a few short
years, we will have available arrays (representing environmental conditions,
certain types of croplands, or certain types of environmental situations) which
will allow the rather rapid evaluation of the disposition and consequent effects of
the release — intentional or accidental, adventitious or otherwise — of a pesticidal
agent or similar compound into the environment.
In order to do this and make it a valid approach, it is my contention that we
must go back to that conceptual model and bring It along with our methodology.
That is, we must develop explicit chemical models, biological models, and inter-
related microcosm models and bring to bear systems analysis, computer simula-
tion, and explicit physical, chemical, and biological characterization of these
chambers to give rigorous scientific approaches to analyzing these kinds of prob-
lems.
*Ecologist, National Ecological Research Laboratory, U. S. Environmental
Protection Agency
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If we had not been successful In other areas at other points in time, I
would say that this would be a hopeless task. However, I am very much persuaded
that we can accomplish our goals. We have had some very good success in
modeling other environmental releases and modeling pharmacokinetics within
animals. In part our success will depend on maintaining cooperation and the
kind of thinking that Jim Hill characterized in one of our meetings on the conceptual
model. Each laboratory can bring fdrth something new, not just In terms of a
disciplinary effort. As we take from the process end and take from the systems end,
then meld them together, we can develop the holistic approach that Dr. Glass has
emphasized. It will not be easy and I cannot guarantee success by a certain date,
but I think we can make real progress. We have seen it Internally, and I hope we
will be able to communicate some of those results to you in a hard document within
the next few weeks.
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MARINE LIFE
Thomas W. Duke, Ph. D. *
Pesticide residues occur in biotlc and abiotic components of coastal
and oceanic environments, and some of these residues have been implicated
in degradation of portions of these environments. Many pesticides can be
detected In tissues of organisms at the parts per trillion level, but the effects
of such levels on the organisms and systems in which they occur are not clear
In many instances. Knowledge of these effects is especially important when
the residues occur In the coastal environment which is a dynamic, highly
productive system where freshwater from rivers meets with saltwater from
the sea. The coastal zone interfaces with man's activities on land and, therefore,
is especially susceptible to exposure to acute doses of degradable pesticides
as well as chronic doses of persistent ones.
Many species are important as human food and spend part or all of
their life cycles In estuaries. It Is Important, therefore, to study the effects
of pesticides on these animals in estuaries where they are most likely to
contact toxicants for the first time. Our laboratory Is well situated for this
study, being located on a large estuary that has more than 100 square miles
of varied habitats and empties into the Gulf of Mexico. The Gulf of Mexico
is the site of shrimp and menhaden fisheries, the nation's chief fisheries in
terms of Income and volume. Approximately 90 percent of all commercial
fishery organisms in the Gulf of Mexico spend at least a portion of their life
cycles in estuaries.
The purpose of this talk is to give you a brief overview of our research
(
\
activities with emphasis on our work with communities and ecosystems as
they pertain to the Alternative Chemicals Program.
* Director, Gulf Breeze Environment;:
Environmental Protection Agency
26J-
1 Research Laboratory, U. S.
-------
A toxic chemical can affect biological resources in two ways: (1) a direct
effect of the chemical on organisms and (2) residues accumulated in organisms
could render these organisms unsuitable for human consumption, thereby
interrupting the supply of the resource to the consumer. At the Gulf Breeze
Laboratory, we study the effect of pesticides and other toxic organics on
marine organisms in the marine environment in which they live. We maintain
a close relationship with the Estuarine Monitoring Program in the Office of
Pesticide Programs, so that we may determine the kinds and levels of chemicals
to use In our toxlclty studies.
We determine the effect of these chemicals on various marine organisms
such as plants, shrimp, crabs, oysters, and fish under controlled conditions
In the laboratory, under semi controlled conditions In experimental tanks, and
In field tests In a natural environment. Laboratory bloassays, both acute
and chronic In nature, use oysters, blue crabs, shrimp, and various fish
tested In flowing water to predict whether a specific pesticide would be likely
to damage an estuary when It Is used In or near It. Of the test organisms,
shrimp are usually the most sensitive to Insecticides. Knowledge of how their
physiology Is altered by pesticides and where the toxicants accumulate in their
bodies contributes to understanding the mechanisms of actions of these compounds.
Also under Investigation are their tolerance to toxicants and how these chemicals
alter fundamental physiological processes and cause physical damage to specific
tissues and organs.
Certain patterns of behavior are essential to the continued existence
of populations of fishes and other estuarlne animals. Alteration of basic behavioral
patterns by sublethal concentrations of pesticides in the environment may subject
the animals to Increased predatlon or to Intolerable physiological stress at
critical stages in their life history. Certain pesticides have ^een shown to alter
salinity preference of specific fish.
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Testing of the effect of pesticides on embryological development and
life history of the sheepshead minnow, a common fish in marsh drainage
ditches, is now complete. Methods of rearing the embryos are being standardized
in preparation for future testing.
Exposure to acutely toxic concentrations of pesticides usually causes
rapid paralysis or death, but effects of long-term exposure to sublethal concentra-
tions are often much more subtle. The damage may be hidden within specific
organisms at the tissue or cellular level. Therefore, a staff pathologist is
investigating pesticide-induced pathogenesis in estuarine animals.
Few data are available concerning the effects of pesticides at the
ecosystem or community level of organization. This is not surprising considering
the complexities of ecosystems and our lack of knowledge of the structure and
function of coastal zones. Effects of pesticides could be masked by variations
in population densities and it would require several years to evaluate such
variations. However, it is possible
to yield information on this complex
to design laboratory and field experiments
system.
Mr. David Hansen of our 1» boratory has worked with an experimental
community that received 10 microgi
ams/liter of a polychlorinated biphenyl and
the community did not recover to a ''normal state" in terms of numbers of phyla
and species after 4 months. Commmities of planktonic larvae were allowed to
develop in control aquaria and in aqu .ria that received the PCB. Communities
that received 10 micrograms per litf': of the chemical were dominated by tunicates,
whereas controls were dominated by
diversity index was not altered by P
individuals decreased.
arthropods. The Shannon-Weaver species
B, but numbers of phyla, species, and
-------
In another experiment, Dr. Gerald Walsh and others of our laboratory
introduced a herbicide into a small pond near our laboratory on Santa Rosa Island.
Applied as a wettable powder in a concentration of one part per million, the
herbicide eliminated the rooted plants in the pond. As the benthic plants died,
blooms of phytoplankton and zooplankton occurred and a normal oxygen regime
was maintained. As benthic plants returned, the number of plankters dropped.
The pond returned to a "normal state" in reference to the primary producers
approximately 3 months after treatment. Such observations, obviously, could
not have been made in bioassays with a single species under controlled laboratory
conditions.
We are cooperating with Dr. Norman Glass of the National Ecological
Research Laboratory in Coi /allis to determine the impact of pesticides on our
"total" ecosystem. We are conducting experiments on the estuarine and marine
portions of the system. To date, we have supplied information for a conceptual
model of such an effect. Also, we have begun studies to establish a marine
microcosm which we can use to determine the impact of a pesticide on the
marine system. As you probably know, at present there are no standard methods
for determining the impact of a pollutant on a marine ecosystem. We are
experimenting with different types of systems and with criteria for determining
impacts on these systems.
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FRESH WATER EFFECTS
John G. Eaton*
I'd like to start off with the disclaimer that most of our work has had an
orientation distinctly different from that which has been discussed or presented
here at the meeting so far. To reiterate some of the things that John Buckley
said, most of our work has been done in response to requests or a need for water
quality criteria to derive water quality standards. Water quality standards allow
the introduction into water of various toxicants, pollutants, or other compounds up
to specified levels or concentrations. The objectives that we have followed in
obtaining these criteria values might be entirely different from those we might
set if the primary orientation were, say, pesticide registration, so please keep
this in mind.
First, although I realize that this might be repetitious to you who have
heard me speak before, I'd like to give you some idea of the scope of our laboratory's
activities. These activities are by no means limited to the study of pesticides.
As a matter of fact, pesticides research is a small part of our program.
Our base laboratory, which is also our largest laboratory, is the National
Water Quality Laboratory in Duluth, Minnesota. It's located on a 13-acre tract of
land on the shore of Lake Superior and was completed in July of 1967. Dr. Donald
Mount is Director of the Laboratory. It consists of a main building having approxi-
mately 54, 000 square feet of floor space, and about half of this is chemistry and
biology laboratory space. Approximately 75 people work there.
In addition to this laboratory, we have three field stations throughout the
country. The Newtown Fish Toxicology Station has been in operation since 1961
and is located near Cincinnati, Ohio on the grounds of a State Fish Hatchery.
*Coordinator, Pesticides Research, National Water Quality Laboratory
267
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About eight people are employed here. They recently conducted a 3-year field study
in which copper sulphate was metered into a 1/2-mile stretch of natural stream in
order to compare its effects in nature with those observed in several prior and
concurrent laboratory chronic exposures.
Another field station, the Western Fish Toxicology Station, is located in
Corvallis, Oregon. The building there has 12,000 square feet of floor space and
facilities for exposing large adult Pacific salmon to toxicants. The major research
emphases at this laboratory are on the effects of supersaturation and heavy metals
on aquatic organisms and on test method development.
The third field station is located at the site of the Monticello, Minnesota
nuclear power generating facility about 20 miles north of Minneapolis on the
Mississippi River. The station consists of eight earthen channels, 16,000 feet
long by 20 feet wide, and a small fish-holding and staff and facility support building.
Initially the channels will be used for the study of thermal effects on fish and
aquatic invertebrates, but subsequently they will probably be used for toxicant
exposures. The site was chosen so that it could use the waste heat from the nuclear
power generating facilities. It has been calculated that it would cost up to $10,000
per day to otherwise heat the water in the channels.
Nearly all our pesticide research has been done at the Newtown laboratory,
at the Duluth laboratory, through grants and contracts, or through interagency
agreements with the Department of the Interior.
One of the most important accomplishments of the National Water Quality
Laboratory has been the development of life-cycle chronic test procedures and
acute testing procedures for several species of fish and aquatic invertebrates. These
permit evaluation in the laboratory of the effects of toxicants on all aquatic stages
of these organisms, including reproduction. These procedures are now being used
in many other aquatic research laboratories besides our own. Several research
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contracts have been completed and others are underway, involving use of these
methods for the study of the chronic toxicity of pesticides and other compounds
and resulting in improvements and modifications. We are continually working to
improve these methods and to devise new ones for additional aquatic species.
Through the use of both short- and long-term tests we have determined
or are in the process of determining the acute and chronic toxicities of compounds
which include 2,4-D, copper sulfate, organic and inorganic mercury, atrazine,
guthion, malathion, diazinon, chlordane, toxaphene, methoxychlor, heptachlor,
lindane, parathion, treflan, captan, several PCB's, DDT, sevin, baygon, fenthion,
propachlor, methomyl, mirex, triton X-100, acetone triethylene-glycol, dimethyl-
formamide, and phthalates. The values derived are used in attempts to estimate
what we call water quality criteria or the quantitative estimates of detrimental
effects to be expected from different levels of environmental contamination. The
criteria are in turn used to derive water quality standards or values defined by
governmental authority as concentrations not to be exceeded. Many of the toxicity
values from our studies have been cited in the document entitled "Water Quality
Criteria" prepared by the NAS under contract to EPA. Among the more urgent
research needs identified by the NAS was the need for additional data on chronic
effects of toxicants and on additional organisms.
Currently we are reviewing a water quality criteria document being pre-
pared by the EPA itself, which will include data made available since the NAS
publication was completed 3 years ago. Such criteria evaluations are extremely
difficult and are largely only educated guesses because they must consider, besides
observed effects, sensitivities of untested organisms, interactions with other
environmental toxicants or factors, and potential effects of associated residues on
other aquatic life, terrestrial wildlife, or man. Communication and cooperation is
therefore necessary among investigators and laboratories representing several
different areas of specialization.
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The National Water Quality Laboratory's data and expertise were also
utilized recently In testimony on behalf of proposed EPA effluent standards. Com-
pounds on the Initial list of nine compounds for which we provided toxlclty Informa-
tion or prepared affidavits were endrln, toxaphene, PCB's, cadmium, and mercury.
As the safety or harmfulness of effluents must ultimately be determined on the basic
effects of concentrations of effluents In receiving waters, essentially the same data
base Is used to derive effluent standards as Is used for water quality criteria.
We have also been Involved to a limited extent in aquatic environment residue-
assessment studies, such as monitoring pesticide and PCB residues In fish from
Lakes Michigan and Superior. We are occasionally asked by outside groups to assist
In Identifying or quantifying residues In fish tissues sent to us from around the country.
These studies often require that we modify existing analytical techniques or devise
new ones. In monitoring the concentrations of pollutants In our laboratory exposure
systems we frequently have to measure very low levels because of the extreme
sensitivities of the exposed organisms. For example, we are talking about levels
such as 0.1 ppb or dlazlnon In water or 0.06 ppb of toxaphene. As shown by water
quality criteria for aquatic life In comparison to the drinking water standards for
several pollutants, drinking water levels for pesticides frequently will not protect
aquatic organisms. Many of the residues or breakdown products we attempt to
Identify have never been Investigated before as far as we can ascertain, and no
methods are available for them. Thus we must have a well equipped and highly
competent analytical chemistry section.
Chronic effects we have observed have been extremely diverse and have in-
cluded lack of reproduction, reproduction but Inability of the eggs to hatch, crippling
of embryos, crippling of fry, crippling of adults, reduced growth, reduced survival,
tendency to convulse, lethargy, hyperactivity, Increased aggression, avoidance,
and many combinations of these. In the case of some toxicants, fish have proven
more sensitive than Invertebrates and vise-versa. These considerations make It
270
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essentially impossible to estimate safe levels of toxicants without conducting some
long-term exposures with more than one species. The big question, of course,
is how many exposures. In the absence of any chronic toxicity data, acute values
have been used in the past by multiplying them by arbitrary application factors
to provide estimates of chronic toxicity, 1/10 or 1/20 being the factors often used
in the case of degradable or cumulative compounds and 1/20 or 1/100 in the case of
persistent ones. Experimentally derived application factors, that is factors obtained
by dividing experimentally determined chronic toxicity values by acute toxicity
values, have been found to vary greatly. Factors ranging all the way from about
1/3 to 1/3000 have been observed. We have often found that the greatest difference
between the acute and chronic toxicity values does not occur in the case of the more
persistent compounds. Application factors of 1/50 for malathion and 1/1000 for
diazinon induce residue LMF's of only about 20 and 25 times, respectively. For
lindane and endrin, on the other hand, which are more persistent, we have observed
AF's of 1/3 and 1/4, but residue BMF's of 500 and 15,000 times, respectively.
Thus a tendency to bioaccumulate is not a good indicator of chronic toxicity potential
to be used when trying to guess safe levels from acute values.
Naturally, the use of experimentally determined chronic test values is
preferred in developing pesticide water quality criteria. However, it is obviously
impossible to determine sensitivities of all aquatic organisms. One alternative is
to find a means of extrapolating from chronic effects on a few organisms to chronic
effects on others for a given toxicant. Test results to date with fish have indicated
that the ratios of acute to chronic test values for several fish species exposed to
a given toxicant are in many cases similar. With some compounds, however, the
ratios have not been very close, indicating that the reliability of extrapolating to
chronic safe values from acute test results is comparably reduced. Such estimates
are still much better than those derived through use of completely arbitrary applica-
tion factors. We are presently making a major effort to evaluate the predictive
271
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capacity of this AF concept by critically reviewing 30 or 40 sets of chronic and
acute toxicity data. We hope to publish the results of this review in the fall or
winter.
We have frequently found that Invertebrate fish food organisms are more
sensitive chronically to pesticides than are fish. Thus the crustaceans and aquatic
insects appear almost uniformly very sensitive to organophosphates, but several
exceptions exist that dictate the necessity of testing other types of organisms also.
We have also investigated biochemical and behavioral methods of estimating
chronic toxicity from short-term exposures. Many chemical indicators have proven
useful in specific instances, but are of limited use because the indicators, often
an enzyme or blood constituent, usually respond to only a single toxicant. Others
such as ACHE respond so generally as to be of limited value for extrapolations
because of wide species variability.
A behavioral response we are working on which appears promising is
the use of the cough response of fish. This is a rhythmic back-flushing of the gills
of fish which normally occurs every minute or so. When exposed to toxicants above
a certain threshold level, the rate of coughing increases, and it has been observed
that this threshold level often corresponds remarkably closely with the concentra-
tions determined to be "just safe" in long-term chronic exposures. Thus for brook
trout, the cough frequency response concentration and the "just safe" chronic toxicity
concentration are 9 and 6 ppb respectively for lindane, 8 and 7 ppb for malathion,
and somewhat less than 10 and 25 for diazlnon. The recording of the cough response
Is accomplished remotely using a physiograph, and while the fish can be left in the
detection chambers for weeks or even months, the determination of threshold levels
usually takes only a few days. The predictive possibilities of this system could be
great and might extend to complexes or mixtures of toxicants as well.
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Another interesting study we have just completed looked at the relative
contributions of DDT-contaminated food and water to chronic toxicity and tissue
residues. Fathead minnows were exposed to DDT in water at concentrations near
the chronic toxicity threshold. Half the fish were fed ground clams that had been
exposed to the same DDT concentrations as the fish, and half the fish were fed
uncontaminated clams. The DDT exposed clams had an equilibrium level of
45 ug/g of DDT residues in their tissues or about 25,000 times the exposure concen-
tration. In addition, the DDT in the clams was radio-isotope labeled so that in
the minnows the fraction of the DDT coming from the food could be differentiated
from the DDT picked up from the water. Clams were used as a food source because
they provided a large amount of food tissue into which we could metabollcally
incorporate DDT residues.
Some of the conclusions from this study were that DDT in the food as well
as the water did increase residues in the minnows and increased the toxicity pro-
portionally. The significance of the contribution due to food was greater at lower
water concentrations, however. Similar responses were also observed in second
generation fish with no apparent increases in toxicity. Some interesting and as
yet unexplainable observations were made on some of the adult fish that were placed
in clean water after termination of the experiment. There was a fairly rapid
elimination of the labeled or food source DDT, but the DDT residues from the
water source changed very little within 56 days. This was not attributable to
differences in the analogues between the two sources because all the food source
analogues we excreted at an equal rate. Nor did it seem to be due to differences in
storage sites of the two different-source fractions, as several tissues contained
the same proportions of labeled and unlabeled DDT. In general, this study provides
some interesting implications in regard to the conducting of chronic exposures with
persistent pesticides. To get a better handle on these we plan to start a similar
study with another chlorinated hydrocarbon with different residue properties in
the near future.
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Along similar lines, we have recently observed that the pesticide mi rex
is much more toxic to aquatic invertebrates when they ingest the pesticide than
when they are exposed to it in water alone.
Other areas in which we are conducting pesticide research are on the
techniques for studying interactions of mixtures of pesticides, the toxiclty of
intermittent or fluctuating concentrations as compared to continuous concentra-
tions of pesticides, the toxlcity of breakdown products and metabolites, and the use
of simulated ecosystems to quantitatively determine effects not just fate and trans-
port of pesticides.
In conclusion, I would like to say that we are in full agreement with the
projects and objectives of the Alternative Chemicals Program. Therefore, we are
anxious to cooperate in the program and to be of assistance in any way we can.
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PRELIMINARY SYSTEMS ANALYSIS
AS A TOOL FOR DESIGN OF RESEARCH PROGRAMS
Mr. James Hill, IV*
To put things in proper perspective, I'm going to talk about a research tool,
which' is at the bottom of Dr. Axelrod's mountains — but that's not of concern to
me because without the foundation there are not going to be any mountains. There
has been a theme running through the symposium which is presented in some of
these short quotes: "The subtle effect of pesticides, " "hidden devils," "secondary
effects," "adverse effects on processes," "the network of roads through plants and
animals to man," and finally "diethylstibesterol affecting emphysema in California. "
All of these quotes refer to system components acting in concert to produce "subtle"
or "hidden" behavior. All system behavior is related to three system processes that
describe everything that happens in any system — transport, transformation, and
storage. Anything that happens with respect to any material can be described in
terms of these three basic processes.
I don't know much about alternative chemicals or pesticides, and many other
materials, but I can still envision them in terms of these basic processes. I'm going
to be presenting a basic research tool that you can apply to the flow of anything.
When I talk about the flow of a substance, I usually think of beer. So when I talk
about a flow, we'll just think about beer and not worry about pesticides or any other
chemical.
What is a conceptual model? Now that's hard to describe because we all
walk around with conceptual models in our minds; models of the way we envision
transports, the world, everything we associate with. We have a concept and it
is modeled in our mental processes.
*Environmental Engineer, Southeast Environmental Research Laboratory
275
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One way we have of communicating this conceptual model is with language.
We use words; we write them down; we speak to one another. And as you've seen
in this symposium, sometimes our language isn't always the same. I don't mean
we speak different dialects or different tongues; I mean we may all speak English
and not understand the words. This is exemplified in a short story.
There was a man and a woman who just had a new child. They had to move
out of their one-bedroom apartment and so they spent some time looking for a new
home. One evening the man came home and said, "I've solved our problem. I
bought a condominium." His wife replied, "Good, I can throw away my diagram. "
Now i don't advocate throwing away the diagrams, because I think they may
be the solution to some of our problems. Diagrams are an explicit, exact method of
communicating conceptual ideas, so from here I'll go to the diagrams.
System Diagrams Represent Conceptual Models
What I'm going through now is a series of diagrams. The wordp on them are
not important. The connection of the arrows isn't important. However, the concept
of building from a basic block that describes your system (your boundaries in time
and space) and then expanding It to the point at which you have a definition you feel is
sufficient to handle the problem Is Important.
In Forrester diagrams of dynamic systems, six symbols are commonly used.
• A solid line represents a directed pathway for transfer of matter
or energy.
• A dashed line represents a directed pathway for control or Infor-
mation transfer.
• The cloud symbol represents a source or sink (input or output) out-
side the defined system boundaries.
• A rectangle indicates storage of matter or energy.
• The valve symbol indicates r^tes along the associated pathway.
• Finally, the circle represents coefficients and parameters that
affect flow rates.
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The degree of resolution or complexity of the Forrester diagram of a sys-
tem may vary considerably depending upon application and resources available for .
evaluating the hypothesis. While there appears to be no upper limit to the resolu-
tion of a model, the lower limit (a single storage component) is demonstrated for a
lake in the following example (Figure 1) from O'Melia. The low level of resolution
in this example does not necessarily imply that there is a better representation for
a particular application.
Figure 1 is Vollenweider's Lake Eutrophication Model. We have an input
from some cloud. The clouds indicate sources and sinks that we're not going to
be concerned about; they may be important in a particular application, but not in
the one that we've described by this diagram. In other words, we're not particularly
concerned where it came from; we're just concerned with where it is after it gets
here. The rectangle is a body of a lake that's completely described for his purposes
by a nutrient concentration. On the right is a flow which is an output. The dotted lines
indicate the influence of effects, but not the actual flow of materials.
In the next diagram (Figure 2) we take this nutrient content in a lake and say,
"That's not very good for our purpose because some of the nutrient is absorbed on
particles, some of it is dissolved in the water, and some of it gets soaked up in the
biota. " Thus we divide up the abiotic component and the biotic component, and we
show a lot of interactions between them.
In Figure 3 the biotic concentration of nutrient is coupled to the biomass
dynamics. You say, "What's the biotic component?" It's clams in the estuary and
they're growing. We want to have them grow, and so their absorption of materials
changes.
In Figure 4 we say our body of water is also divided up into areas that have
different dynamics and different processes associated with it. In terms of this lake
we have a surface layer, epilimnion, hypolimnion, and sediments, each one inter-
acting through settling and wind turbulence and things like that. This is just a
rough Indication of some of the processes that can affect you here.
277
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Figure 1
Vollenweider Lake Eutrophication Model
1
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t
Input Rate
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/ i
Nutrient Concentration
—- =—-(o* q)Mw where M» = concentration of nutrient,
J = flux of M to lake.
o = sedimentation coefficient,
q = flow coefficient, and Z = mean lake depth.
278
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Figure 2
Nutrient Model for Lake with Biotic and Abiotic Storage
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279
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Figure 3
Possible Coupling of Biomass (B) Subsystem with Nutrient Concentration (Mb) Subsystem
Concentration in
Biotlc Component
[Xj Uptake Rate
Output Rate
Death Rate "°]X1
Respiration
280
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Figure 4
Vertical Representation of Stratified Lake
Atmospheric
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x -v Parameters
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281
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Now, we're going to take the surface layer and In the next diagram (Figure 5)
we're going to expand that and show some of the chemical/physical processes that
affect the material that was in the surface layer. On the right is the concentration
of a pesticide or what have you in the surface layer of the water. This interacts
with solar energy because it has a food web, and we have photochemical degrada-
tion some place on there, and precipitation input. We've divided the material into
inorganic participates and organic participates, and it's just a whole bunch of pro-
cesses that affect the surface layer. Similar processes affect the epilimnion, the
the hypolimniun, the sediments, etc.
The next diagram (Figure 6) shows how in the surface food web we can have
a similar expansion. We can call them primary producers, consumers, second
consumers, and decomposers. This certainly doesn't include all the food web, but
at least it includes the primary important parts that give you the essence of your
dynamics.
The last diagram (Figure 7) combines all the transports, transformations,
and storages previously discussed into one picture. It is overwhelming and so we'll
go very quickly to Figure 8.
This is a diagram (Figure 8) taken from an article by Wassily Leontief in
Scientific American, and it's demonstrating the structure of the American economy.
Now, I don't find this nearly as complicated as that diagram that I just showed you,
and yet they have similar information content. You can go from a complicated diagram
to this array with columns and rows labeled leather, food and tobacco, lumber and
wood, electricity, textiles, etc. The squares in each of the blocks represent the flow
of goods or products from, say, apparel and textiles on the left to agriculture on the
top. Well the people that work in agriculture have to wear clothes. There's an
interaction there.
If you go from those diagrams that I showed you to one of these arrays with
squares in them, all of a sudden arrays with squares aren't too hard to under-
stand. The diagrams might have been complicated but the array isn't.
282
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Figure 5
Some of the Storages, Processes, and Subsystems Associated
with the Surface Layer Storage Component
(toncentratloO(^^?"!V>) Water Column .
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-------
Figure 6
A Skeletal Abstraction of a Food Web
to
s
Respiration [XI
,
(XI Respiration |
, j SorptlonCXI
1X1 Sof?tlon 1
{ Respiration [X]
[XI Srttnng
[XI Sorption |
Particulate Organic Matter
1
J
4
1
Decomposers
* : L_J
[XI Sorpllon I
-------
Figure 7
A Minimal Representation for a Pesticide in a Dimictic Lake
(Part 1)
CO
oo
en
ICBMcaMTMmoM I ^^
at ntamt line f ^S
»»SSMftJ:r
-------
Figure 7
A Minimal Representation for a Pesticide in a Dimictic Lake
(Part 2)
to
oo
-------
Figure 8
Developed Economics*
•i •%> G-< (•*
\^^^^^^\\>X\^^
7?- fy^V* •V/,0,fr<$c> ^ ^Of^^^fyq^^ /^ ^ (. c p i,/^
j.
16
%&&"*< ^
LEATHER 1 ; •:•-..
FOOD AND TOBACCO 2
FISHING 3
MISCELLANEOUS
INDUSTRIES
MACHINERY 5
IRON AND STEEL 6
MONFERROUS ML'TALS 7
NONMETAL MINERALS 8
PAPER 9 3 \n
LUMBER AND WOOD 10 'B-
I
RUBBER 11 j1,-.:
WPAREL AND TEXTILES 12
CHEMICALS 13
AGRICULTURE 14
ELECTRICITY 15
COAL PRODUCTS 16
COAL MINING 17 jj
l»
PETROLEUM AND 1fl
PRODUCTS w
TRANSPORT 19
TRADE AND SERVICES 20
HOUSEHOLD SERVICES
*From Leontief, W. "The Structure of Development." Scientific American
September 1963.
287
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Now, If you'll let me call that array with all the boxes in it a matrix, I'm
into mathematics and we don't have to worry about the diagrams. We can throw
the diagrams out now! The Idea that I'm trying to get to very strongly is (1) we
all have these conceptual models, (2) we can put them into simple diagrams,
(3) we can make the diagrams more complicated, (4) we can take the complicated
diagram and turn it into a matrix, and (5) we can go to linear or matrix algebra
and make some statements, some logically strong statements. These statements
are dependent upon the assumptions you made when you drew your first diagram
and all the assumptions along the way.
The rest of my talk is concerned with the type of statements that you can
make as a tool for preliminary design of a research program. You have a problem
with the flow of any substance; for example, beer from the Mississippi River into
an estuary, and you want to handle the first approach — nobody's ever looked at
beer in the Mississippi flowing into the estuary. You need to know (1) what to
measure, (2) how often to measure it, and (3) how precise and accurate your measure-
ments have to be.
Preliminary Analysts Techniques for Linear System Approximations
If we take an array similar to that of Figure 8 which represents a complicated
diagram and replace the shaded squares in the grid by numbers which are equal to
their area, then we have a matrix which represents a first order approximation of a
mathematical model of the original concept. This matrix, call it "A," has numerous
properties which can be investigated mathematically and then translated into state-
ments about the system under study. These statements are approximate and as such
cannot tell us all about the system. However, they can help us to ask the right ques-
tions of the system in a research program.
What do you measure? Some of the interaction coefficients, the values in the
A matrix, may be determined by analysis of the inputs and outputs of the system
using a technique called component analysis. Thus if we know the input of beer to
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the Mississippi and the output of beer from the Mississippi, then component analysis
can tell us if it is possible to determine the rate of storage of beer in the sediments
of the river without direct measurement of the storage. So from the component
analysis on your preliminary description of your system, you can say, "What do I
have to measure and what can I find out cheaply by just measuring the input and
the output and plugging that in the machine ? "
The array of Figure 8 from Wassily Leontief is related to economic input/
output analysis, which has been introduced into ecology by Bruce Hannon in a
recent article in the Journal of Theoretical Biology. This flow analysis gives you
a measure at steady state (i. e., when things have settled down with a given input)
of the amount of flow between one storage compartment in your model and another.
If a flow is really small and the interaction with the system is small, then that's
one you may not want to spend too much money on measuring. You'll go for the
big flows as they're predicted by your model, and then you can go check that in the
field and revamp your model and work it around again.
How often do you measure these things ? Well, a group of graduate students
at the University of Georgia and Hank Shugart, who's with the Oak Ridge people
now, have shown that an ecosystem's frequency response is very accurately described
by a second order system approximation. This means that you can take two blocks
in your model and lump your whole ecosystem into them with respect to the frequency
response analysis. In other words, if you ask how fast things are going to change
when you change the input of beer to the Mississippi River, then that frequency
response is reasonably dependent on a second order approximation.
You make a second order approximation based on the matrix and this gives
you back what we call an undamped natural frequency. This natural frequency is
related to how fast your ecosystem, your system whatever it may be, is going to
change, and that gives you an approximation of how often you want to measure what
it is you have to measure on the system.
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Finally, with respect to accuracy and precision of the measurements,
there's a sensitivity analysis. This analysis can tell you how much effect on some
measure of total system behavior a small change in any one of those coefficients
represented in the A matrix or on your diagram is going to have. In other words,
if the input of beer at St. Louis is very large, but a change in it of one glass more
or less is going to really affect the clam production in the estuary, then you'd
better be very accurate in your measurement of that beer. Even though the number
may be very large, you're going to have to know a small deviation. If way upstream
the input may be small and changes that are double and tripling aren't going to have
much effect based on sensitivity analysis, then you can use a very coarse measure-
ment or maybe even ignore the measurement completely.
All of those analytical techniques are available right now and they're very
straightforward. There's one more that I'd like to talk about which I call topologlcal
analysis.
The actual behavior of a system as represented by the diagram depends
on four things — the inputs to that diagram or to the system itself, the coefficients,
the topology that you hypothesize (in other words, is the leg bone connected to the
neckbone) and the structure which includes how the rates flow through that topology
to influence other rates (e.g., how does diethylstibesterol affect emphysema in
California?) So with respect to those four levels of
analysis deals only with whether you hypothesize that the leg bone is in effect
connected to the neck bone and you leave out the rest of the body.
This analysis I hope is going to be available within a year's time, and it
will turn out to be quite useful in a very real aspect. We talk about going from the
test tube to the field, from the laboratory to the ecosystem, and this topological
analysis is one measure of what you gain or lose when you do that.
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If you hypothesize in your representation that grasses, a field crop, can
uptake beer and affect mice that's one thing. If you hypothesize that grasses are
divided up among seeds, stems, leaves and roots, and each of these individually
with different rates of beer transport affect mice (e. g., the mice absorb more
beer from the seeds than they do from the roots because of their feeding habits),
then what do you lose when you lump all the grasses into grass without paying
attention to the seeds, stems, leaves, and roots and their separate interactions?
Simplicity is gained but there are many things which you may lose. Most of them
might be referred to as richness of behavior. Topological analysis provides one of
the measures of richness of behavior.
Now if you combine all five of these analytic techniques and use them as
a cheap linear approximation, a first step toward looking at something that you're
not used to looking at or toward looking at something which you have always looked
at with a mind toward describing instead of analyzing, then it may give you a good
way to save some money In your research program. That's what I'm advocating.
Summary of Preliminary Analyses
Topological analysis is currently being developed by a group of Dr. B. C.
Patten's graduate students at the University of Georgia. This technique is intended to
allow determination of the influence of the topological structure on system behavior.
Such information is useful in evaluating alternative system structures and particularly
in determining the effects of reduction or aggregation of components.
Flow analysis or input-output analysis is based upon the manipulation of
the A coefficient matrix in the linear, donor-control approximation. Briefly, a matrix,
G, is generated by „
G = E A1
1=1
in which each element, G , is a relative measure of the fraction of flow out of storage j
that appears as input to storage i under steady state conditions. This information may
be used to identify important processes or flow paths in the system.
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Sensitivity analysis may be used to evaluate the effect of a parameter
perturbation, v(t), upon the storage levels In the system. The measure of sensitivity,
S, is useful In determining which parameters have a prominent effect upon system
behavior. A linear approximation of S(t) Is determined from
d S(t)
dt
a x,
S(t)
v(t)
where the terms In brackets are Jacoblan matrixes. With a unit perturbation of each
parameter, A , the steady state values of S for each storage variable may be used
as a relative measure of system sensitivity to each parameter.
Frequency response analysis provides frequency related measures of system
behavior. Both the referenced papers and current studies Indicate that the damping
ratio (*) and the undamped natural frequency (^ ) are well described by a second-
order control system approximation of the system. When the system Is overdamped
(most ecosystems appear to be so), then the undamped natural frequency becomes
a measure of the maximum required sampling rate for system variables.
Component analysis allows numerical determination of a limited number of
coefficient values from the A matrix of the linear, donor-controlled representation
and the system transfer function as determined from experimental input-output data.
Topological analysis can be used as an aid in evaluating the influence of
connectivity upon process rates in the system. Flow analysis can provide a measure
of steady state distribution of flow through the process pathways. A preliminary
sensitivity analysis can determine the effect of an error in parameter estimation upon
storage levels and hence upon flows. These three evaluations of process-system
interaction provide criteria for elimination of components that have the least effect
on system behavior, thus systematically reducing the graphic representation.
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These analyses may be applied to a mathematical approximation of the
reduced representation. This results in information that may be used as a first
approximation in choosing measurement methods and sampling rates for evaluation
of system hypotheses.
Selected References
Child, G.I., andH.H. Shugart, Jr., Frequency Response Analysis of Magnesium
Cycling in a Tropical Forest Ecosystem. In: Systems Analysis and Simulation in
Ecology, Vol. n, Patten, B.C. (ed.). Academic Press, New York, 1972. p. 592.
Eberhardt, L. L., R. L. Meeks, and T. J. Peterle, Food Chain Model for DDT
Kinetics in a Freshwater Marsh. Nature. 230: 60-62, 1971.
Harmon, B., The Structure of Ecosystems. J. Theor. Biol. 41(3): 535-546, 1973.
Hill, J., IV., Component Description and Analysis of Environmental Systems.
Masters Thesis. Utah State Univ., Logan, Utah. 1973. p. 94.
Leontief, W. W., Input-Output Economics. Oxford University Press, New York,
1966.
Moore, N. W., A Synopsis of the Pesticide Problem. In: Advances in Ecological
Research, Volume 4, Cragg, J. B. (ed.). Academic Press, New York. 1967. p. 75-128.
O'Melia, C. R., An Approach to the Modeling of Lakes. Hydrologie. 34:1-33, 1972.
Patten, B.C., W.G. Cale, J. Finn, and R. Bosserman. Propagation of Cause in
Ecosystems. In: Systems Analysis and Simulation in Ecology, Vol. 4, Patten, B.C.
(ed.). In Press.
Tomovic, R., and M. Vukobratovic, General Sensitivity Theory. Elsevler, New
York. 1972.
Webster, J.R., J.B. Waide, and B.C. Patten, Nutrient Cycling and Ecosystem
Stability. In: Mineral Cycling in Southeast Ecosystems, Howell, F. (ed.). AEC
Symposium Series. In Press.
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DR. BUCKLEY: I would suggest that this is an appropriate time for ques-
tions, and again I'd like to sit down and leave the question answering to Dr. Glass
and his colleagues. I'd make only one observation first, and it stems directly from
the last presentation. And it is something that concerns me and I'm sure it con-
cerns all of you here — how do you put the bits and pieces of information that we
have together ? How do you interpret the significance of the different odd facts,
sometimes pleasant and sometimes unpleasant, and how do you deal with the ques-
tion of their significance, how do you deal with things as a whole?
And I can assure you we don't have all the answers, but we surely are
interested in pursuing this, and I do think that the aggregate of what we've just
heard is aimed in that direction.
DR. NORMAN GLASo: I think it's obvious from these presentations
-i
- too that this is a new program, which will have far more output in the near and
distant future than it's had in the last few months, but I think it's also clear that
we're trying to adopt a more or less holistic, integrated type of program. I'd
like to Invite any questions you might have at this time, addressed to anybody
on the panel.
MR. ALFRED MITLEHNER: I suppose this question goes to Dr. Axelrod
as much as anyone else, and that is in view of the very preliminary nature of the
information discussed and presented here this morning, how does Dr. Axelrod view
this information with regard to the establishment of criteria for the classification
of pesticides ? More specifically, are we really ready to establish specific criteria
that would relate to the classification of pesticides ?
DR. AXELROD: It's a multifaceted question, and I think I can answer
you best by congratulating Mr. Hill on a genuinely new black-box look at some
of the problems that we in the Agency must address ourselves to now and in
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the future. I'm not too much on models, and particularly mathematical models
in the past, but I think the approach of systems analysis, the engineering approach,
and almost bilogically cybernetic approach introduced here this morning by Mr.
Hill and his colleagues may eventually solve some differential equations simultan-
•
eously. Approaches such as Dr. Cooper from Michigan State has taken in the
area of ecology, where one pinpoints the input/output from the black box as a
systems analysis and the major thrust becomes one of understanding exactly
what makes that ecological system run, is the type of research which will in
the final analysis answer what in science might be considered mundane questions,
but which are paramount to a regulatory agency.
Many millions of dollars are spent in litigations, in argumentations, and
adversary approaches. Very little of those arguments are based on sound,
predictive concepts, and it's not just for this Agency, but it is for the benefit of
agriculture and the industrial sector which addresses itself to the agricultural
community that we have intelligent data inputs of predictive value for solving
problems before they become adversary problems.
The adversary is the last final common denominator of ignorance, and
the solutions there become ones of judgmental values and legal matters, but not
of science. I think that relationship between the type of — and I say this very
much in a double quote — blue sky that Mr. Hill approaches, or Dr. Cooper, or
people of his abilities, is one which impacts directly on the ability to solve
problems and issues including the classification problems in the future. You
cannot solve problems today based on a meager information feedback system.
You have to plan for the future, and your inputs financially, resource-wise and
manpower and brainpower-wise, are the only answers to intelligent future
decision-making and policy-making.
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There Is a real paucity In the data banks of knowledge. There's only
a few days' worth of corn left out there; there's only a few hours left in the
ability to predict on a scientific basis many of the problems and issues that are
involved in this Agency. And I think that the dollars and resources we put into
the type of work that these people enunciated up here, and particularly for a
base line of what Mr. Hill is doing, will serve a great purpose in resource
conservation in the courtroom later on, when we can have data bases to predict
from values on a statistical basis.
MR. CHARLES KRISTER: Can we get back to the real world ? If
Dr. Korp is not here, I'll direct this to Mr. Hill.
Can we direct our attention to the microcosm that's very important
to industry. Has any thought been given to making a study of the ecosystem in
the Pesticides Regulation Division ?
I would hope that the Pesticide Division would be one of the first systems
to be studied and, again, to find out what the important factors are that should
be involved In the input — get Into that black box that some of us have been in
quite a while.
DR. BUCKLEY: I'd take that as a comment and not as a question, Chris.
That may be a good time for us to go have a cup of coffee. There will be oppor-
tunity for questions later, and before we do break this up I do wish to thank my
colleagues for a fine presentation this morning.
DR. BUCKLEY: I would like to Introduce now the second half of this morn-
ing's program. Until now we have talked about ecological and environmental con-
siderations, but I assure you that In my view of the world, man fits In those models
that Jim Hill was talking about.
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To make one point before we go on to health, I don't know whether it's •
entirely clear or not, but the people who sat here this morning in the earlier part
of this program are geographically located in different places. The point that I
want to make is that they talk together and they know one another. We have a single
program which in a sense is tied together in the generation and interpretation of
data to be used in a conceptual way such as that that was described by the very last
speaker, Mr. Hill. I didn't want anyone to get the impression that everything is
all in one place.
The other point I want to make is that we feel no compulsion to be the
generators of all data. In fact, as this progresses and the development of under-
standing and interpreation goes on, we would like to feel free to call on all of you,
those of you in other Federal agencies, those of you in academia, and especially
those of you in industry, to help us not only with the data that you may already have
provided in some fashion or another to the Federal government, but also with new
data which we can use in this way.
We'd like to be completely open in exchange of views and in telling you why
we want information and how we're going to use it. We've tried to tell you with
this conceptual model what we're up to. The boiled down version of this is that we
want to understand what's happening.
I feel one further need to make sure that you understand that I am in the
research end of the business, and my colleagues who were and are now on the
platform are in the research end of the business. I want to draw a very clean
and neat distinction between what research and researchers do and other activities.
It seems to me very clear that research must provide the scientific basis
on which decisions can be based. It owes an evaluation of what risks or hazards
may take place under a given set of circumstances. It owes this in as explicit a
fashion as it can make, and it owes this to the people who do make decisions. It
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also owes an obligation to refrain in the presentation of such data from implying an
action that should follow.
In summing this up, it's a summation of what's known and a summation of
what's not. An indication of what gaps there are, but refraining from saying
"research must be carried out to fill these gaps. " I think that's an entirely dif-
ferent issue. There may be other gaps in other fields that are more important
in a priority way, and I think that's an administrative decision, wholly separable
from the research process. I'm trying to express to you a set of feelings that I
personally hold very deeply, that I hope will be reflected more and more in the
documents that the Environmental Protection Agency produces as scientific back-
ground documents.
We expect to spend some days next week with another set of people talking
about this very topic, and this I think is something that with great good fortune we
will find more and more the case in background documents across all areas in the
environment — not just those concerned with pesticides. This is a gratuitous lec-
ture, not on the schedule, but nonetheless one that I feel our stock in trade is depen-
dent upon — being able to unemotionally and as clearly as possible express what will
happen, and, equally, to refrain from the conclusion that this should or should not
happen. That's not our business as researchers.
Now I may in fact put on a different hat, and at the time that I put that on,
I feel entitled to one vote along with others as to what the Agency may do with the
information. It is Important to distinguish between what I know as a researcher
and what I believe or prefer as an Individual member of society.
Now with this set of gratuitous comments out of the way, I'd like to turn
to the human health aspects part of the program.
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INTRA- AND EXTRAMURAL HEALTH EFFECTS RESEARCH
Ronald F. Baron, Ph. D. *
I handed out a little brochure called Intramural and Extramural Health
Effects Research, and I'd like to call your attention to a couple of things. The
first page relates to this Alternative (Substitute) Chemicals Program. This whole
listing of tasks, of areas of interest to our laboratory, is our FY '75 program
plans. The first page is what we are going to be doing in this program. The next
few pages relate to other ongoing programs within our laboratory in health effects
and chemistry. I must point out that we have combined both health effects and
chemistry.
I would also like to point up another document which may be of value to
some people, the EXPRO-75. This is our extramural program for '75. I don't
want to go into detail with regard to our extramural and intramural programs. I
would like to point out with regard to these plans — most of them not fully imple-
mented, some of them not even fully planned — that these are areas of research
in which we are going to work.
With regard to EXPRO-75 and the brochure I'll be very glad to answer
questions with regard to the Substitute Chemicals Program at this time. Any
questions relating to any other areas of research in that document should be pre-
sented at some later time, either here or in Research Triangle Park, North
Carolina.
This discussion will center around the scope of work and the ultimate
goals as observed in 1974, what we have accomplished and how, and what we will
do in our health effects program at Research Triangle Park.
*Physical Science Administrator, National Environmental Research Center
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At this point, I would like to diverge from this planned discussion of our
Alternative Chemicals Program to comment on a very specific question or a
series of questions has been raised relating to pesticides used for research
in this program.
Questions have been raised as to the quantity, quality, and sources of
material which were originally designated as compounds of interest, substitute
chemicals, alternate chemicals. Approximately 6 months ago a decision was
made to obtain a quantity of material to be used in the entire research program
when applicable, to maintain uniformity at least in the material being used.
This effort is a throwback from several years of experience in Food and
Drug and from what I have heard of happenings in USDA in which research per-
formed over a period of several years was never fully substantiated because of the
lack of quality control of the chemical used. Thus, as I mentioned, a decision was
made to obtain a sample of material, either through industry cooperation or through
the purchase of single or multiple large batch lots, and to store the samples in a
single repository to be disseminated as needed.
»
Within the framework of the chemical contaminants program, we are
maintaining a repository in which pesticides are to be stored under the conditions
which would allow maximum storage with consideration of the conditions of safety
and stability of the product. In all instances it was determined that the majority of
sample material would be stored in bulk at sub-freezing temperatures in an inert
atmosphere and the samples to be sent out would be repackaged into smaller
quantities of approximately one pound, one pint, or less and would be stored in
desiccators at sub-freezing temperatures. An attempt would be made to obtain a
100-pound or 50-kilogram sample of material. Now I know this has raised many,
many questions and I'll attempt to resolve some of them.
This quantity of material that was requested was not evaluated on the basis
of any individual pesticide nor on the basis of the toxicology of any single pesticide
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or even any group of pesticides. The request for 50 kilograms had nothing to do
with any individual compound, but was made only on the basis of the overall general
program. The only consideration was that a sufficient quantity of sample should
be available for a potentially 4- or 5-year program to allow adequate quantities of
research in all areas that we can at this particular point anticipate.
In particular, a large quantity of sample was thought to be necessary with
regard to one particular program. It was thought to be necessary for a potential
chemical contaminants program, which I'm going to go into in a few minutes.
We had decided that we would be interested in a chemical contaminants
program in which a level of 0.05 percent of a technical mixture of material would
be of interest to us. What the interest is is debatable at this particular point. We
may be interested in the toxicology; we may be interested in the chemistry. But
at any rate we decided at this particular point several months ago that a contaminant
present at the level of . 05 percent would be of interest.
I did some quick calculations and found that if we wanted to obtain this
contaminant material which would be present at . 05 percent, 100 pounds of material
would yield a sample of about 25 grams of this contaminant. Now this means if we
were to take this whole 100-pound lot and were to extract it and were very good at
purifying, we could get out a sample of 25 grams.
This is wholly illogical. We're not anticipating this, but if it was necessary
to obtain a very, very small impurity that was very, very significant and we needed
a 25-gram sample for chemical evaluation or toxicology or long-term feeding studies,
our 100-pound sample would yield us only 25 grams. I want to point out that this
goal of isolating a contaminant from this vast quantity is one that we never expected
to reach, but we want you to know that we considered it.
I'd like to point out that we did not fully take into consideration the toxicology
of the individual pesticide when requesting a 100-pound sample. A sample of 100
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pounds of material such as Temik or aldicarb would certainly not fall into the same
category as a 100-pound sample of material such as atrazine or captan. Thus, we
must be faulted, and I'll take full responsibility for not considering all aspects and
especially the toxicologlcal aspects when we brought up this idea of 100 pounds. In
most instances a 5- to 25-poound sample would be more than sufficient for all of
our studies.
A consideration was made of the source of material for the study. In the
chemical contaminants program, sufficient funds were provided for the purchase
over the counter of sufficient quantities of material to allow us to continue the pro-
gram as I have specified.
However, an attempt is currently being made to obtain, through the co-
operation of industry, the necessary pesticides in an effort to allow industry to be
a part of this program, to maintain its own source of reference material for the
program, and if necessary to question and discuss any results on the basis of their
own studies with their own compounds.
I think it would be rather difficult to fully accept the consequence of using
material purchased outside of the currently available manufacturing sources, as
too many things can happen to a sample after it has left the manufacturing plant.
I would like to point out that the product we were interested in obtaining for this
study is a technical product, and we would like the material that is available at
"the end of the stream of manufacturing. "
In no instance, even though we asked for a technical product, would we
be interested in disrupting the manufacturing process to obtain a sampling of
material prior to its final removal from the factory. In short we are interested
in the material as it leaves the plant for shipment and becomes available for the
formulators and subsequent handling.
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In some instances It was pointed out that a technical product is not avail-
able but a formulated or semiformulated product might be available, and I wish to
point out again that if this is the product that leaves the plant, this is the product
in which we are interested. If a pesticide is manufactured as a technical product
and is formulated or partially formulated in one operation, then this is the product
we would like to use. I wish to emphasize that we do not and did not wish to inter-
rupt the technical production of pesticides to obtain a sample for our research.
It has been suggested that we should obtain for this activity a sample con-
sisting of mixtures of several batch lots to assure reproducibility of the manu-
facturing system. It has also been suggested that since there may be several
manufacturers of a known product, we would want to use several manufacturing
products for our studies. We further questioned the choice of material wanted for
this study with regard to whether we were to use a technical or actually formulated
material and what we were going to do about the toxicity of diluents in our program.
We considered these points and decided that we would use a single technical
material, so that if there was a problem we might be able to Identify it immediately.
By this I mean we would not want to take a sample from several different manu-
facturers or from several different manufacturing runs within the processing plant
and lump them together.
We decided that we were going to attempt to determine if there were dif-
ferences in products of several manufacturers. We were and are able to obtain
samples of such materials. These are the same or similar materials produced by
different manufacturers. As pointed out a little while ago with regard to the re-
pository and storage of materials, we attempted to devise a system in which minimum
problems in storage and maintenance of the material would be encountered. The
material is to be stored at sub-zero temperatures in an inert atmosphere in an
attempt to maintain the material for a period of 4 to 5 years.
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In addition, it is anticipated that industry would maintain a similar sample
of the material, and any questions raised on the integrity of the material would thus
be verifiable. Now just this morning one of our colleagues here raised another
point which I hadn't considered: What do we do at the end of the program when we've
got 95 pounds of material left over? Would we send it back for their disposal or how
would we handle it?
I have to admit we have not fielded all the questions, and I'm very grateful
that we've had this opportunity to get together and have some of these raised. At
this point I can't answer the question of what would happen if we had 95 pounds of
a material that's very toxic left over in our repository. If the energy crisis con-
tinues, I think we'll know what to do with it, but I really don't know at this particular
point. We would probably request a little bit of help in disposal.
These are some of the questions that we have considered with regard to
this request of a sample of 100 pounds of material which has raised many, many
eyebrows. I would like to ask if there are any more questions, or if there are any
more feelings about this I'd like to try to respond to them. But right now I'd like to
go into the direct aspects of the program. My primary purpose and mission is to
give you a little background and information as to what we have done with regard to
the program up to this point.
I've broken this program into two areas, toxicology and chemistry, and as
I said before they are so interrelated it's going to be difficult to disconnect them.
A program is underway right now within the framework of what we call chemistry
for the optimization and full evaluation of a GLC detector, the Hall-Tracor Detector,
for the sensitive detection of nitrogen, halogen, and sulfur-containing pesticides.
This detector is being evaluated for use in the analysis of pesticide residues
in environmental samples. At present the microelectrolytlc conductivity detector
as generated by Dr. Hall from Purdue University has been shown to be sensitive and
selective to halogen, nitrogen, and sulfur-containing materials and approaches the
electron capture detection in sensitivity.
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The detector does not respond to most of the substances that interfere with
EC detection and has a wide linear range. When fully optimized the detector will be
of value to all researchers in the field of pesticides and contaminants. It will pro-
vide not only a much needed sensitivity and a confirmatory technique, but might
even replace the electron capture for routine determinations.
Studies are currently in progress to optimize and evaluate the detector for
selective sub-nanogram sensitivity to sulfur-containing pesticides and their metab-
olites, as well as for the determination of chlorinated materials. The studies will
attempt to demonstrate the usefulness of the detector for differentiating chlorinated
pesticides, poly chlorinated biphenyls, poly chlorinated napthalenes, and low levels
of other materials. In addition, work will be performed in the area of response,
reliability, and ease of operation of this particular detector.
Another area of interest is the extension of currently available clean-up
procedures to include pesticides'not generally included in a multiresidue detection
system. These materials might be the materials which are substitutes for deregis-
tered pesticides.
In addition an effort will be made to integrate liquid chromatography as a
clean-up and separation procedure for the multiresidue detection system. Initially,
methodology must be developed for pesticides which do not fit into accepted schemes
of multiresidue methodology. Alternations of known methods such as the Mills
procedure or the Shafik procedure will most likely result in acceptable recoveries
for pesticides not presently included in existing schemes.
The introduction of liquid chromatography may provide analytical chemistry
with a technique for the routine determination of very hard to evaluate chemicals.
Two other areas of interest include the identification of toxic impurities in techni-
cal grade material and toxicological evaluation of materials found to be impurities
of interest.
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This latter lexicological area is addressing itself to the idea of fulfilling
toxlcity screening and testing procedures necessary to provide data to fill out the
data base as specified within the framework of the OPP review program. This
effort will provide capability for oral, dermal, and inhalation exposure to small
mammals; it will provide the toxicology input following review procedures to fill
out the data base.
The scope of this work is divided into two main areas. The first one, pro-
bably the most important one, is to respond to inquiries for data from the ongoing
review process, and this is to respond immediately to inquiries. The second is to
respond to inquiries for data on compounds derived from the studies on the char-
acterization of impurities of interest in the technical formulation.
It had been anticipated that several compounds would be reviewed over the
first year and that data would be missing in the toxlcological evaluation. These data
would be requested and ultimately the Pesticide and Toxic Substances Effects
Laboratory would provide a rapid turn-around time in the response to these inquiries.
The chemical contaminants program consists of several parts. One, as
mentioned before, we will maintain a repository for all pesticides to be used in the
study by all researchers.
Two, a theoretical organic chemistry paper evaluation. This is a paper and
pencil evaluation of the manufacturing process used by the industry for pesticides of
interest. As suggested by the patent and open literature, an evaluation is to be made
of the synthesis route. An effort will be made to determine whether toxic impurities
are present or can be formed within the framework of the synthetic routes being
followed or the ones that we know about.
It is anticipated as evidenced on the basis of dioxins and benzofurans pro-
duced in the synthesis of chlorinated aromatic compounds that the possibility exists
for a number of impurities. It has been considered that in the preparation of such
materials as parathion, the reaction of dimethylthiophosphorochloridate might result
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in TEPP. Without anticipating that revelations such as this would be of any major
consequence, it is reassuring to believe that this would be the only contaminant that
could be expected under a particular synthesis procedure.
It is anticipated that in this paper exercise, the industry might cooperate
with EPA in allowing the conditions to be known under which the compounds were
actually synthesized. If such information concerning synthetic routes is not forth-
coming, then all information would be reviewed from the patent and open literature.
Trade secrets — and I believe this is an area that one might consider to be
a trade secret — in the evaluation of the synthesis of a product will be maintained at
all times. On the pesticides to be used in this program we will do a preliminary
analysis which is predominantly a GC assay followed by mass spec and a computer
analysis to determine on a "rough and dirty scale" the impurities in an analytical
mixture.
This preliminary screening will be followed, if deemed necessary by the
background information we have obtained by the paper synthesis evaluation route or
even by our own quick and dirty method, by other techniques for the isolation or
characterization of impurities. At this particular point possible attendant toxico-
logical studies would be considered.
The objectives of this particular program are to chemically identify im-
purities and contaminants in the technical mixtures which may present problems
and if necessary to evaluate the toxicological significance of the impurities.
It is estimated in this work that many synthetic routes would be evaluated.
It is also estimated that there may be a small number of compounds that would be
evaluated that may have to go into further detailed chemical analysis to elucidate
their structure. I want to point out, as I said, that all compounds that we are going
to use in this particular structure are going to be evaluated on the quick and dirty
analysis. Some of this information is available and may be made available to us.
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We will, however, run through all the compounds quickly. There will be
very few compounds which will have to be studied on a large scale. I want to
emphasize — and I've heard this word used — I want to emphasize that this particu-
lar program is not in effect a "witch-hunt" for pesticide impurities that will destroy
or raise questions on the efficacy of the compound for use in agriculture.
Rather, it is the sole aim and goal of this testing procedure to prevent or
attempt to prevent with hindsight, the occurrence of another tetrachlorodibenzodioxin
contaminant program as we all know originated with 2,4,5-T.
The last and major thrust of PTSEL's program is to provide information on
the inhalation toxicology of pesticides. I would like to point out at this time that the
research aims of our program are two-fold. One, primarily to respond to questions
raised within the framework of the review function to fill out a data base, and two,
to perform research in areas of known deficiencies in which toxicological information
would be of value in the overall assessment. In this instance it was defined that
inhalation toxicology is an area in which data are not available in most instances and
certain data would be of value in an evaluation of a pesticide.
The area of inhalation toxicology was considered to be of such importance
that a new program, at least new to our pesticide laboratory, has been generated and
has been divided into five phases. These five phases are, briefly, generation of a
respirable particle, chemical analysis of the chamber content, acute toxicology,
gross and microscopic pathology of selected tissues, and clinical chemistry.
The first phase of the work includes the generation of respirable particles
in the general range of 1- to 3-micron size; this is a very artifical figure and has
only a small relation to the pesticide size range obtained in agricultural use. Sig-
nificant questions have been raised within the framework of this effort as to the
significance of the work other than on the basis of a toxicological evaluation and not
an environmental or a use pattern evaluation.
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The use of a highly respirable particle, although artificial with regard to use
in agriculture, will be of value in the initial phases of this effort. Toxicity studies
will be done to compare the oral, dermal, systemic, and inhalation routes of admin-
istration of some of these materials to rats. Inhalation studies would include 1-hour
or 4-hour exposures. It has generally been considered in the framework of this work
that we would anticipate lower toxicity values for the inhalation route, and the sig-
nificance of these values would be evaluated and future studies conducted to determine
their actual worth.
At the present time we can only call them reference materials. Gross and
microscopic pathology will be carried out routinely on lungs, with additional histo-
logical examination on selected tissues when such study is considered valuable. The
clinical chemistry analysis will include analysis of liver, kidney, lung, blood, and
various other tissues for thj presence of pesticide, not classical clinical chemistry.
We've called it clinical chemistry. It is actually analytical chemistry for pesticide
residues in the body.
It is anticipated that this program would allow EPA to utilize inhalation
capability as a part of the toxicological assessment of what we're now considering
to be substitute chemicals. I would like to get across a major thought: Our laboratory
exists for two purposes. These purposes are to do research in the particular areas
that we find need research and are of interest to the regulatory arm of our Agency
in Washington, and to directly respond, to fill out our data base as deemed necessary
by the C&E Division in its reviews.
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LONG-RANGE HEALTH EFFECTS
John L. Buckley, Ph. D*
I've already said In a couple of different sessions here what I thought the
needs and goals of EPA research in relation to health and pesticides were, and I
simply wish to reiterate those very briefly.
Predominantly it's a matter of methods development, and the part that I'm
particularly concerned with now is methods development that will be quicker,
better, and cheaper, that will let us know with a greater degree of assurance at
an earlier time what effects occur in man as a result of a particular exposure. The
areas I wish to emphasize are the long-term, low-dose aspects — carcinogenesis,
mutagenesis, in particular, and to some extent teratogenesis.
I think we probably would all agree that in the area of mutagenesis — and I
heard this expressed more cogently and clearly by others — we don't have a good
method. Each individual who carries out a particular method will defend that up
to a point, but the fact is he's not all that certain when he gets through how you
interpret his results in relation to man, and that's where the question really is.
We're kind of fumbling around in the dark along with, I must say, the rest of the
scientific community. We're prepared to support work, some of which will almost
certainly not pay off, but we think that comparative studies and attempts in different
ways and support of sometimes far out ideas may well be useful in this area. From
this we hope eventually to contribute to better methods of assessing effects of
chemicals in general, and in this case perhaps specifically.
As to other activities that we have, I picked out carcinogenesis, and again
I don't want to step on the toes of NCI or other groups concerned predominantly
*Acting Deputy Administrator for Program Integration, U. S. Environmental Protection
Agency
Preceding page blank 311
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with this area. But all of you who are in the chemical business know better than I
that this is a magic word, that if it's associated with a compound, it's pretty close
to a death knell for the compound.
We've got quite a lot of information on tumor formation in various and
sundry animals, but we do have a big problem in extrapolation of animal data to
man. Here again, as in mutagenesis, we'd like to improve our abilities to ex-
trapolate in this area. We really are not all that interested in tumor rates in rats
or mice or monkeys for that matter, and I'll make an observation as an ex-wildlife
manager, that I'm not even that much interested in it in most kinds of wild animals,
simply because few animals in a wild population live long enough for anything of
this sort to be significant in terms of the population.
So whatever we do in terois of carcinogenesis, even though we do it on
other organisms, we are really doing in order to understand probabilities of these
kinds of effects in man. Now you can fault us, perhaps, on the contracts that we
let, the interagency transfers that we have, or the research that we ourselves carry
out, but you cannot fault us, I believe, on the goals that we have in trying to support
this kind of research. This research is to enable us to make better judgments than
we can now on whether the substance of .interest, whatever it may be, causes in
man the effects that we are looking for.
That really is what the game is. As a population biologist and not as a
human health specialist, it's with some temerity that I stand before a group such
as this and speak to the topic of human health, and for that reason if for no other
I'd like to wrap it up there as far as comments on human health.
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DR. AXELROD: So often expressed from the podium," I have a compulsion
coming on," and it relates to some of the things that John said, all of which I agree
with, but I would make a more or less philosophical expression of trepidation at
this point, and that relates to the place of the scientist in the American society —
things that Phil Handler at the Academy had discussed and others. And I think it's
important that the scientist take his proper place in our society, and that there is
in the vernacular no "cop-out" for expressing his concerns and his data banks in
any process, and law, and any regulation that impacts on himself as a human
being and as a scientist in general, so I'm sure that John and I both agree that the
scientist In EPA has a proper place In the decision-making process.
DR. BUCKLEY: Yes, Len and I have talked about this over lunch and no
»
doubt we will talk about it back at the office too. The only point that I feel very
strongly about and I've already expressed is that there are some things where
scientists should feel prepared to stand and beat on the table and say "this Is the
way things are."
But to the extent of saying we should do something because of that informa-
tion, I think that's a very difficult step that we all wish to weigh. Here I will demand
my right to a vote as a member of society, but I'll try and refrain from imposing
my scientific views and confusing those with my social views. Are there questions
either of Ron or of myself?
MR. JOHN J. HOOD: I have a question for Dr. Baron. Following his so-
called quick and dirty review of these various technical materials for contaminants
and/or Impurities, what will be the criteria that will be followed for further scrutiny
of these materials ?
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DR. RONALD BARON: We've made up some arbitrary numbers to go along
with our quick and dirty study as to how much further we will go after we've done
our quick and dirty study. For anything that would be present in a level of . 05
percent and above it would be considered of value to know what the compound is and
what the identity of the material is. If on identifying the material or if on the basis
of the paper evaluation, the material is thought to have some toxicological properties
that we're interested in, we will go further in that respect.
If the material is present at a level of . 1 percent in the technical mixture,
we will probably make a considerable effort to get the material Identified. We may
not go any further than GC mass spec and the computer analysis of the peaks, but we
will make an effort to identify materials at. 1 percent; . 05 percent is sort of a flag.
DR. R. E. HANSON: When you talk about quick and dirty and in the same
breath you talk about levels of 0.05 percent, I just don't believe you can talk quick
and dirty. A total analysis of some of these compounds would cost you in the terms
of 1 to 2 man-years or more, and I know, we've spent it. And yet you're going to
look at levels at . 05 percent of compounds you don't even know are there. I just
can't seem to understand what you're talking about quick and dirty with what I know
about total analysis of pesticides and contaminants at the . 05 level.
DR. BARON: It's an interesting statement you just made. I don't hear a
question in it, but I would like to respond to your statement in that I agree with you
totally. The quick and dirty approach to this is a reflection on two things. One,
for the major thrust of our research program in all aspects of research we' want
to know what we're working with, so we are planning on putting these materials
which are capable of being put through the GC with a mass spec and a computer
analysis of the peaks that come out to determine quickly what is there, and if the
material shows up on a chart paper as being a contamination and If It looks like It
could be part of that which we're interested In, then that peak would then go through
the mass spec. We'd then come up with a series of potential compounds that It
could be.
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This is not going to be a major undertaking with all the pesticides in our
programs. It's obvious that it cannot be. I want to point out that it can be a quick
and dirty. I don't really think that there's going to be a major thrust to identify or
to pull out and try to identify all of the small pieces of technical mixtures.
DR. BUCKLEY: I, as a nonchemist, have no right to speak to the details
of this. I have, however, been associated with investigations of various and sundry
pesticides long enough to know that invariably there are questions as to whether it's
the technical material,, the intended active ingredient, or just what that causes
some observed effect. I think the question of trying to sort this out is real. I
think the point of knowing, to the extent you can, the makeup of the substance being
toxicologically or environmentally or otherwise investigated is clearly worthwhile.
I think all of us can think of horror stories where we've used different substances
and ended up with contradictory results.
You may well fault us on the details of what we tell you we want to do.
We will certainly solicit your advice on how we should do some of this. I would
make one further point, that in my view, the place we start is asking you to tell
us, as clearly as you can and as far as you're willing to, the makeup of the pro-
duct which you provide us. It seems to me that for us this is really the most
important starting point.
There is a matter of timing and sequence here. If we were to look through
all pestictdal chemicals, looking for what the contaminants are or what the Ingre-
dients are or what the average composition is or things of this sort, we have in
front of us an endless chore. If we do have a particular question on a compound,
in the sense that we see an observed effect which either is inconsistent with what
we would have expected to be the case, knowing something of structure and function
in related compounds and so on, or if for other reasons it seems important to look
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at this, as was the case with the dloxlns In 2,4,5-T, then I believe we ought to do
It. I have, nothing further to say on the topic, but I don't Intend to close off discus-
sion at that point.
DR. JOHN MCCARTHY: Ron, as I understood your description of the Inhala-
tion program, It was to determine the acute LC 50 of materials that needed such
information. Are there other plans beyond that based on results from those tests ?
DR. BARON: At this particular point in time, we are finding our way as to
what we're going to do. We have two major areas of pesticide inhalation research
programmed, but they don't relate to what we are going to do with the acute toxicity
data.
The two other areas that are being considered for further work are utilizing
Inhalation — and I'd like to reemphasize that we consider inhalation to be another
means of entry, not the same in quality, but just as oral or dermal, it is another
mode of administering a compound for metabolism studies — and we are planning
to give some serious consideration of this question of particle size distribution
in actual life and how our studies on a very respirable particle relate to what we
can consider to be an agricultural or a problem in actual use.
So these two particular areas of particle size, distribution and effect, and
metabolism — and because we do have a very good reproductive physiology group
at Research Triangle Part, we will probably be going into reproductive physiology
as affected by inhalation as a route of administration. I hope that answers some
of your questions. I know I walked around your question very nicely. I can't
really put my finger on what we're going to do with the data when we compare these
four routes as I've said. This is our feeling process at this point.
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DR. JERRY SMITH: One statement and one question. The emphasis was
given on development of new methodology and trying to come up with short and
quicker ways of assessing toxicity hazards. In this area are we not getting to the
point where we are duplicating some of the efforts of NCTR ? In addition, I would
encourage us not to do method development on unknown materials that are under
evaluation but to do our method development on materials about which we know the
most. The question relates to the statement yesterday that we should do more of
our studies knowing what the effect of the materials are in man. Do you have any
intentions or any plans for doing metabolic studies or other work in man with pes-
ticides under consideration, so that more appropriate experimental animals can be
selected for these studies ?
DR. BUCKLEY: I'd rather respond to your statement than your question.
It is not our intent to duplicate anything at NCTR. In fact some of the funds that
we're talking about are used at NCTR, and they in fact are a supplement to that
program. I have no intent from my point of view of seeking a broadening or dupli-
cation of effort here. I'm sorry that Morris Cranmer is not here today. I guess we
didn't arrange things very well that way, but he could have answered that or com-
mented on the statement somewhat more precisely.
As to the studies in man, I think it's probably fair to say that at this junc-
ture in time I know of no plans, no arrangement for volunteers or otherwise,
nothing definite. Neither do I rule out the possibility or the desirability of doing
this. I think probably many of you here are much more aware than I of the parts
of the world in which one now does human studies, and the things which lead to
this, and I would rather not comment further on that.
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Nonetheless, I do want to make the point that the effect on man, or the lack
of effect on man preferably, is the goal of this whole set of things that we are talking
about right now. I'm sure that I've evaded the question rather than answered, but
it's the closest I can come right now.
QUESTION: You have at Research Triangle a health effects group under
John Knelson. You also have inhalation work going on at the NIEHS. Are you
tied in with these groups or is this a separate group ?
DR. BUCKLEY: The group under Dr. Knelson is a different labotatory in
the same research center under the same overall leadership, and the answer
then is yes, we are clocely tied in. The answer at NIEHS is that we have free and
frequent exchange among people at all levels. When we have meetings planning
work in relation to any topic at Research Triangle Park, I think it's fair to say
that the people from Dr. Rail's staff participate with us and we with them. My
personal biases are that you have the work that you need done in the most appro-
priate place that you're able to find. I feel no compulsion to see that EPA has all
the talents that it needs to do everything it might be asked to do in-house.
So, the short answer is that we're not trying to take over all the research
in the world. We are trying to fill in some rather explicit gaps which now exist.
We are trying to support other people in doing things which we find are worthwhile,
and we hope that we buy the most with the taxpayers' dollar in the process of doing
this.
DR. GORDON NEWELL: I've heard several comments during this meeting
about the relevance of our studies as they apply to man; certainly many of my bio-
chemist friends here know that today we can use fresh human liver (from necropsy
cases) to conduct preliminary metabolism studies on compounds of concern. We
can identify the human in vitro metabolites and then study the compound in various
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animal species; in certain laboratories this is a regular practice. Although this
approach is not as satisfactory as using the whole animal, at least it gets you one
step closer to man. Studies with drugs often are concerned with efficacy, but
here we're concerned with safety. Through the comparative metabolism approach
we now can obtain a more realistic understanding of a compound than we could a
few years ago.
DR. BUCKLEY: I think other points of the same sort, of course, are in
comparative pharmacology, comparative physiology, and comparative metabolism.
The points and questions that have been raised that the animal model reflects systems
of responses of Interest in man deserve much more attention in selection than has
been given in the past.
QUESTION: I dlcui't see any reference at all in your health effects work
relating to epidemiological estimation of cause and effect relationships on popula-
tions, possibly international comparisons and that sort of thing. I know the Office
of Pesticides has the function in the technical services division, but it occurs to
me that maybe some of this type of work could be addressed by you also in relation
to this program.
DR. BUCKLEY: It's difficult to respond to this in a nonbureaucractic way,
and the only point that I would like to make is that the proof of the pudding is in the
eating, as It were, and to the degree that one can look at what really does happen
in the world in terms of man, this Is clearly the most satisfying thing that you can
do. I personally think that there are a number of epidemiological opportunities
that have not yet been adequately exploited — not all of them in this country.
Either with funds associated with this program or with other funds, it is our Intent
to try and exploit some of those — exploit in the sense of Invest resources in them.
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You know, without saying that we will do research on the following things or
support epidemiology, I would submit that there are parts of the world where cer-
tain kinds of chemicals are used and the exposure levels are considerably higher
than they are In other circumstances, and the populations at risk are sufficiently
large that one may be able to observe effects If present where one cannot observe
them In relatively small numbers.
There are, you know, many Ins and outs of this, and I would hope that we
can exploit this source of Information. On the other hand, there are some other
kinds of epidemiology In a sense that trouble me. Some of the cohorts of people
available for study are relatively so small that the expectation of whatever event
Is searched for Is not likely to show up. The Infrequency of things just sort of beats
you, and so there are many things that one would like to do epldmlologlcally which
really are not practical that way.
Now, someplace between this rather negative view that says if you can't
find out what you want to know, don't bother doing it, and on the other hand saying
that man is the only final proof of this and If you don't see It in man you can't believe
it, it does seem to me that there are some real and important opportunities for
epldemlologlcal work which ought to be and I hope will be carried out.
DR. R. E. HANSON: I think part of Industry's concern has been that we
know there are compounds picked for the program, we have been requested for
technical material, yet the people that are requesting the material do not seem to
have any data case in front of them. I would like to know who we present the data
base case to, number one the data that's already within the files, and second, any
new data that we have in our own files that has not been transmitted forward, but
I think we get an Impression that you're working In a vacuum.
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And yet you're telling me you want us to come to you. Well, we're happy
to come to you, but who are we coming to? Are we coming to Len, to John, or to
both? I think this is part of my apprehension, because we know one of our compounds
is picked. We've been asked for the technical product. Yet we haven't the foggiest
notion what you're really going to do, who is telling you what to do, and what kind
of base case you already have in front of you that says I shouldn't do this, this,
and this, because it's already been done.
I look down through your whole list, and for the particular compound I'm
thinking about if you use the classical techniques that are already there, I have to
say it's already been done, and this I think is the little funny feelings I get about
what's going on with the program is you seem to work for the same Agency, but then
I'm not sure.
DR. BUCKLEY: Well, may I suggest that the communication between us
and you has been less than adequate, and may I hint that perhaps the communication
between those of us inside EPA may, in fact, have been less than adequate. May
I suggest that we're working reasonably hard at fixing this. We'd like to share more
openly with you than we have.
We want to share with you what it is that we want to do and why we want to
do it. From my perspective, we'd like your advice and assistance. For you to
tell us that our plans are stupid won't hurt my feelings in any way, and for you to
tell me that you already have this information and we are welcome to it, will
certainly please me.
Now, as to the first part of your question, whether you should address
it to me or to Dr. Axelrod, I think probably it really should be to Len, because
our understanding on this in a general way up until now has been that the contacts
with industry were initially largely to be through his office rather than mine. I
think that with that having been done, and it has, I would think that the time has come
for closer exchanges and particularly at the technical detail level between my people
and yours.
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And the point I want to make here is that I'm troubled a little bit because
I can conceive of 25 or so different individuals dealing with different parts of this
program in my organization coming and asking for essentially the same kind of
thing. We had thought that would be annoying to you and we've tried to turn it
off. On the other hand, there is the fact that the person who wants something is
likely to tell you with more precision why he wants it and lay at rest any questions
there may be about it than the other way around. We are in fact trying to arrange
so that we will set up a first set of contacts, which then may broaden so that the kinds
of questions and kinds of comments that you make now will be adequately addressed.
As far as requests to you for compounds, it's our intent that this be through
Dr. Baron, and if there are detailed questions beyond that we'd like to take it up and
pursue it. I'm sorry for the disruption and confusion which obviously has arisen
in this program, and the reason that we asked Ron to say some of the things that
he did, to include this explicitly in his presentation this morning, was to try and
get out for public discussion and clarification what it was we were about and why.
And if the details don't satisfy you, in the way in which it has been explained
and discussed, then I would like to pursue this further, because I see no gain in having
mistrust, worry, and discomfort on the part of any of you or of us.
DR. KORP: I just wanted to say how really pleased I was to be here all three
days of this meeting. I've heard a great deal, I've learned a great deal, Fm very
appreciative. The suggestions were fine.
We will take advantage of all your suggestions. We will pay attention to
them, those where we can find something reasonable and feasible, we will implement
improvements in this program and in our programs. I look forward to seeing you all
again at some meeting at Washington headquarters or at your companies. I thank
you very, very much.
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DR. AXELROD: I'm not quite sure if I understood everything John was
saying, but you've got to understand as we put our cards on the table, this program
was impacted on us very, very quickly, and it's really only recently that there have
been many clarifications in the thrust of the program and its implementation. I
think where some of the confusion lay was that one area was a "review concept,"
the other was "research" to be carried out by ORD in the various geographic locations.
I think that what was discussed this morning really related to something
that was to be and is to be implemented at the research level, and that was studies
of some of the impurities in some of the compounds. In that respect let me say that
not all syntheses would or could lead to the types of impurities that John was talking
about for further study, so that we're not cutting across all. If a particular synthesis
could lead to an obvious problem of toxicological effects, then those specific compounds
would be studied.
It was confusing because as someone once said, "Throw a pencil, throw a
fit, but throw something," and we had to get this program going for many obvious
and some perhaps not too obvious reasons. I think that the communication lines were
very clearly delineated henceforth. I think that the one place where there was a
question was in who do you go to for what, who's asking for what, and why are you
asking for it.
I think that just at the level of strict interpersonal relations, everyone is
entitled to know in writing why something is wanted. I think that in the review areas —
and we've had very good fortune in this area — there has been a good liaison developed,
so that in the particular compound of our interest, a number of companies have come
forth with their data bases. And at least in one case the data was much more than
we could retrieve from the literature or from our data banks and registration, and
it became obvious that certain aspects of further study would not be necessary,
because there was more data that was brought to us from the company than we could
possibly achieve from outside information sources.
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I think that all of you In Industry who have some trepidation left concerning
the flow of Information systems will be satisfied by a rather rigorous and concerted
effort to delineate point for point who's on first and who's on second. And hopefully,
we're all on home base, so that you all get letters that say "For this piece of the
action please address your comments to X, Y, and Z or preferably just to X.
I think what John said about too many people, "too many cooks spoiling the broth"
is very appropriate.
We have two or at a maximum three points for data retrieving and for
contact, depending on where the thrust is. Obviously, we want to minimize the
number of letters, the number of round robins and information retrievals, and
certainly the trepidation that goas with all of that, because of wasted time and wasted
effort.
In the areas of the basic research In John's operation, there would be
obviously a contact point for the type of thing that was wanted, I. e., a certain
amount of compounds. Where there Is the review process It would be sent to a
headquarters contact point, perhaps In our office, for getting back a package, but
If you all paid attention to that schematic placed on the screen yesterday by Ken
Olsen, you would see that In the proper way, In the best of systems, before anything
happens, the corporation Is contacted. We sit down and at that point decide what
we want, from whom we want It, and for what we want It.
DR. BUCKLEY: I have a few observations that I think will not take more
than a couple of minutes. They're a reiteration of things I've said several times.
First, I feel very strongly that It's Important to ask the right questions in a research
frame, and the right questions Involve dealing with the world as it really Is, and not
a kind of a hypothetical world. Associated with this, is the question of the significance
of any observable fact. The answer to the question "so what ?"
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I think we've seen at this meeting, some evidence of misinterpretation of
information, and we've also seen some information which is undoubtedly accurate,
but wholly irrelevant. In other terms, this is sometimes thought of as a red
herring, and this area of interest is no more devoid of red herrings than most
other fields.
It does seem to me that the phraseology of the question to be investigated
is really important. I think of a point outside of the pesticide field that I would use
to illustrate this. At a meeting in Athens, Georgia, some months back a man was
explaining that in a small test tube system he was using, he had demonstrated that
bacteria were able, with materials that occur in the environment, to produce
nitrosamines. I began to pursue the question in somewhat more detail to deter-
mine the conditions that prevailed — temperature, pH, concentrations, etc.
It's not a question of "could it?" The question is, in the world as it is,
"does it?" The point I want to make is that we haven't always been very careful
in the questions that we've asked, and we haven't always made the best possible
interpretation of the significance of what we've found. The major of Jim Hill's
presentation here this morning, which in my view was one of the highlights, is
the capability of putting it all together, of putting things in their proper perspec-
i
tive, of evaluating the' relative importance of various events and observable facts.
We'll continue to work on this kind of a framework, and we earnestly
contributions of knowledge and data that we can use in these kinds
solicit your
of interpretations.
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I'd like to close simply by saying that when.I came to this meeting I felt
somewhat as though I were walking into a miasma of suspicion, but I leave with a
very much better feeling than that I arrived with. I would hope that our coopera-
tion can Increase in productiveness for us and for you, and that we won't let sus-
picions that arise "pressure cook" until they become unbearable. I'll bring mine
to you if you'll bring yours to me. Thank you all.
END OF PROCEEDINGS
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Agenda
p
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EPA SYMPOSIUM
Alternative Chemicals Program
With an Overview of
Pesticide Research and Development
OBJECTIVES
To acquaint the pesticide industry and
academia with the Alternative Chemicals
Program and its review processes.
To present the status of the EPA Alternative
Chemicals Program and pesticide research
and development activities.
To provide an overview of U.S. and world-
wide pesticide research and development
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TUESDAY. AUGUST 13, 1974
7: 30 - 9: 00 p.m. Conference Registration
Convention Corridor
WEDNESDAY, AUGUST 14, 1974
Alternative Chemicals Program Organization
and Review Processes
Dr. Henry J. Korp, Moderator
South Ballroom
8:15 Late Registration
9:15 Welcome and Introduction
Functions and Overview of the
Office of Pesticide Programs:
Highlights of OPP Programs
Dr. Henry J. Korp
10: 00 The Alternative Chemicals Program:
Purpose, Organization, Operation
Dr. Leonard R. Axelrod
10:30 BREAK
10: 45 The Alternative Chemicals Program:
Flow Charts and Key Decision Points
Mr. Kenneth O. Olsen
11:15 OPP Liaison
Dr. Frederick W. Whittemore
11:45 BUFFET — Central Ballroom
1:00 Panel Presentations and Discussions
Dr..Leonard R. Axelrod,
Moderator
General Description of the Initial
Scientific and Mini Economic Review
Prci
Ger
Bio
Re'
3:00 BREA
ess
Dr. Thomas D. Burkhalter
Mr. Jeff Conopask
.ral Description of the Full
phere and Socioeconomic
ews Process
Dr. Lamar B. Dale
Dr. Arnold L. Aspelin
3:15 Progress in EPA Research:
New [j rections and Overview
I Dr. John L. Buckley
6: 00 REC 3TION — Buckingham
7:00 DIN R—Buckingham
To\ rds a New Perspective on
Pe; ides
Dr. Henry J. Korp
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THURSDAY. AUGUST 15, 1974
Overview of Worldwide Pesticide Research
Dr. Morris Cranmer, Moderator
South Ballroom
9:15 Worldwide Perspectives of Pesticide
Research
Dr. Frederick Coulston
9: 45 The Role of WHO In Pesticide Research
Dr. Frank C. Lu
10:15 The Role of FAO in Pesticide Research
Dr. Edgar E. Turtle
10:45 BREAK
11:00 U.S. Participation in CODEX
Mr. Lowell L. Miller
11:30 International Topic
Prof. Radojica Klajic
12: 00 LUNCH — Central Ballroom
Regional Role in Pesticide Programs
Mr. Robert Harding*
1:30 National Environmental Pesticide
Monitoring Program
Dr. William Murray
2: 00 What the USDA Does in Pesticide
Research
Dr. Phillip Kearney*
2: 30 What the USD! Does in Pesticide
Research
Mr. Jerry Longcore
3:00 BREAK
3:15 From Industrial R S D to the Marketplace
Dr. Edwin F. Alder
3: 45 Research and Special Considerations:
Nonagr(cultural Use Pesticides
Mr. Melvin Carbett
4:15 The Future of Pesticide Research:
A Challenge
Dr. Leonard R. Axelrod
*Speeches not available for publication
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FRIDAY, AUGUST 16, 1974
Pesticides Research in the Environmental
Protection Agency
Dr. John L. Buckley, Moderator
South Ballroom
8:30 Introduction
Dr. John L. Buckley
Ecological Effects
8:45 Overview
Dr. Norman Class
8:50 Terrestrial Effects
Dr. James Cillett
9:15 Marine Effects
Dr. Thomas Duke
9: 40 Fresh Water Effects
Mr. John Eaton
10: 05 Fresh Water Transport Processes
Mr. James Hill
10: 30 Question and Answer Period
10:55 BREAK
Human Health Aspects
11:10 Intra- and Extramural Health Effects
Research
Dr. Ronald Baron
11: 40 Long-Range Health Effects
Dr. John L. Buckley
12: 10 Question and Answer Period
12:40 ADJOURNMENT
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APPENDIX II
Participants
Mike Adair
The Ansul Co.
Edwin F. Alder, Ph. D.
National Agricultural Chemicals Association,
representative
Vice President, Lilly Research Laboratories
David C. Andreassen
Pesticide Accident Officer
Environmental Protection Agency, Region II
Arnold L. Aspelin, Ph. D.
Chief, Economics Analysis Branch
Office of Pesticide Programs
Environmental Protection Agency
Leonard R. Axelrod, Ph.D.
Director, Criteria and Evaluation Division
Office of Pesticide Programs
Environmental Protection Agency
Richard C. Back, Ph. D.
National Agricultural Chemicals Association,
representative
Union Carbide Corp.
Ronald L. Baron, Ph. D.
Chemist, National Environmental Research
Center
Environmental Protection Agency
F. Ray Barron, Jr.
Manager, Plant Industry Registrations
American Cyanamld Co.
Joan B. Berkowitz, Ph.D.
Project Director
Arthur D. Little, Inc.
T. A. Blue
Manager, Agricultural Chemicals
Stanford Research Institute
Jerome J. Breiter, Ph. D.
Washington Corporate Representative
Hercules, Inc.
Glenn E. Brussell
Manager, Registration Section
Chemagro
John L. Buckley, Ph. D.
Acting Deputy Assistant Administrator for
Program Integration
Environmental Protection Agency
Thomas D. Burkhalter, Ph. D.
Plant Studies Branch
Office of Pesticide Programs
Environmental Protection Agency
Terry L. Burkoth, Ph. D.
Manager, Toxicology and Registration
Zoecon Corp.
William T. Carlson
Chief, Agricultural Branch
Smithsonian Science Information Exchange
Barry Commoner, Ph. D.
Director, Center for the Biology of
Natural Systems
Washington University
Jeff Conopask
Economic Analysis Branch
Office of Pesticide Programs
Environmental Protection Agency
Joseph Cotruvo, Ph. D.
Pesticide Program Analyst
Office of Program Management
Environmental Protection Agency
Frederick Coulston, Ph.D.
Director, Institute of Comparative and
Human Toxicology
Albany Medical College
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Morris F. Cranmcr, Ph. D.
Director, National Center for
Toxicology Research
Lamar B. Dale, Jr., Ph. D.
Acting Chief, Metabolic Effects Branch
Office of Pesticide Programs
Environmental Protection Agency
Thomas W. Duke. Ph.D.
Director, Gulf Breeze Environmental
Research Laboratory
Environmental Protection Agency
David W. Duttweiler, Ph.D.
Director, Southeast Environmental
Research Laboratory
Environmental Protection Agency
Don F. Dye
Coordinator, Regulatory Affairs
Chevron Chemical Co.
Norman E. Dyer, Ph. D.
Chief, Pesticides Branch
Environmental Protection Agency, Region VI
Jack D. Early, Ph. D.
Manager, Government Relations
Monsanto Co.
John G. Eaton
Coordinator, Pesticide Research
National Water Quality Laboratory
Environmental Protection Agency
Carl D. Emerson
Chief, Technical Assistance Section,
Pesticides Branch
Environmental Protection Agency, Region VII
W. B. Ennis, Jr., Ph.D.
Staff Scientist, National Program Staff
Agricultural Research Service
U. S. Department of Agriculture
Herbert E. Evans
Manager, Pesticide Labeling and
Distribution
Helena Chemical Co.
Homer E. Fairchild, Ph. D.
Chief Liaison Officer, Industrial Affairs
Office of Pesticide Programs
Environmental Protection Agency
Robert B. Foster
House Appropriations Committee
Richard W. Fresh
Chemical Specialties Manufacturers
Association, representative
Environmental Advisor
O. M. Scott & Sons
Mel Garbett
Chemical Specialties Manufacturers
Association, representative
James W. Gillett, Ph. D.
Ecologist, National Ecological Research
Laboratory
Environmental Protection Agency
Norman R. Glass, Ph.D.
Director, National Ecological Research
Laboratory
Environmental Protection Agency
Harvey S. Gold
Chemical Specialties Manufacturers
Association, representative
Director, Regulatory Division
Velslcol Chemical Corp.
Robert E. Hamman
National Agricultural Chemicals Association,
representative
Manager, Government Relations
Ciba-Gelgy Corp.
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R. E. Hanson, Ph.D.
Manager, Pesticide Registration Department
Shell Chemical Co.
Robert W. Harding
Environmental Protection Agency, Region VIE
Herbert H. Harris
Product Registration Coordinator
Diamond Shamrock Chemical Co.
William M. Henry
Project Manager
Battell e - Columbus
James Hill, IV
Environmental Engineer
Southeast Environmental Research Laboratory
Environmental Protection Agency
James L. Hilton, Ph. D.
Chief J Pesticide Action Laboratory
U. S. Department of Agriculture
William L. Hollls, Ph.D.
Science Coordinator
National Agricultural Chemicals Association
John J. Hood
Vice President, Agricultural Division
Ciba-Gelgy Corp.
Kenneth J. Hood, Ph. D.
Terrestrial Ecologist
Ecological Processes and Effects Division
Environmental Protection Agency
H. M. Hubbard, Ph.D.
Division Director
Midwest Research Institute
Francis M. Hunt
Government Relations Manager
Dow Chemical Co.
Hiroshi Ikuma, Ph.D.
University of Michigan
Erling M. Jensen, Ph. D.
Program Manager
EG&G/Mason Research Institute
Earl N. Kari
Deputy Director, National Environmental
Research Center
Environmental Protection Agency
Dean Katsaros, Ph. D.
Technical Vice President
Nor-Am Agricultural Products, Inc.
Harold E. Kazmaier, Ph. D.
Chief, Technical Assistance, Pesticides
Environmental Protection Agency, Region I
Philip C. Kearney, Ph. D.
Chief, Pesticide Degradation Laboratory
Agricultural Research Service
U. S. Department of Agriculture
James O. Keith
U.S. Fish and Wildlife Service
Stephen Kellner
Director, Legislative and Regulatory
Affairs
Chemical Specialties Manufacturers Association
Radojica Kljajic, Ph. D.
Head, Pesticide Department
University of Belgrade
Henry J. Korp
Deputy Assistant Administrator for
Pesticide Programs
Environmental Protection Agency
Norman E. Krapf
Chief Chemist
Vineland Chemical Co., Inc.
Charles J. Krister
Manager, Product Registration
DuPont Co.
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4
Donna Kuroda, Ph. D.
Physical Science Administrator
Office of Program Integration
Environmental Protection Agency
Margareta Lambert
Supervisor of Technical Service
Nor-Am Agricultural Products, Inc.
August B. Lindquist
Manager, Product Regulations
Stauffer Chemical Co.
Jerry R. Longcore
Fish & Wildlife Service
U. S. Department of the Interior
Frank C. Lu, M. D.
Chief, Food Additives
World Health Organization
John F. McCarthy, Ph.D.
Manager, Registration Functions
FMC Corp.
Donald D. McCollister
Manager, Government Registration Group
Dow Chemical Co.
Everett D. Marvin, Jr.
Sales Manager
Kerr McGee Chemical Corp.
Lowell E. Miller
Assistant for Legal and Regulatory Affairs
Office of Pesticide Programs
Environmental Protection Agency
Alfred W. Mltlehner, Ph.D.
National Agricultural Chemicals Association
representative
Manager, Agricultural Chemical Research
and Development
Unlroyal, Inc.
H. Anson Moye, Ph. D.
University of Florida
William Murray, Ph. D.
Director, Technical Services Division
Environmental Protection Agency
Paul O. Nees
Contracts Administrator
WARF Institute, Inc.
Gordon W. Newell, Ph.D.
Director, Department of Toxicology
Stanford Research Institute
Ken O. Olsen
Program Manager, Criteria and Evaluation
Division
Office of Pesticide Programs
Environmental Protection Agency
Edward O. Oswald, Ph. D.
Chief, Chemistry Branch, National
Environmental Research Center
Environmental Protection Agency
E. George Pazianos
Kahl Associates
William Phillips, Ph. D.
Chief, Ecological Effects Branch
Office of Pesticide Programs
Environmental Protection Agency
Robert A. Poss
Chief, Pesticides Branch
Environmental Protection Agency, Region X
Gerald W. Probst, Ph.D.
Director, Elanco Regulatory Services
Ell Lilly and Co.
Jean E. Pulllam
Program Coordinator, Criteria and
Evaluation Division
Office of Pesticide Programs
Environmental Protection Agency
Martin H. Rogoff, Ph. D.
Associate Director, Registration Division
Office of Pesticide Programs
Environmental Protection Agency
3B.
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Daniel L. Shank land, Ph.D.
Purdue University
Jerry M. Smith, Ph. D.
Manager, Toxicology Research
Rohm and Haas Co.
John M. Stackhouse
Vice President
National Agricultural Chemicals Association
Brian T. Sturgess, Ph. D.
Environmental Protection Agency, Region DC
Charles R. Swanson, Ph.D.
Laboratory Chief, Southern Weed Science
Laboratory
U. S. Department of Agriculture
Ely M. Swlsher, Ph. D.
Manager, Government Regulatory Relations
Rohnf and Haas Co.
Edgar E. Turtle, Ph.D.
Food and Agriculture Organization of the
United Nations
Antony J. Vithayathil, Ph. D.
Washington University
Rosmarie von Rumker, Ph.D.
RvR Consultants
Kenneth C. Walker
Assistant to Administrator,
Agricultural Research Service
U. S. Department of Agriculture
Alfred E. Wechsler, Ph. D.
Vice President, Environmental and
Blomedlcal Systems Unit
Arthur D. Little, Inc.
R. R. Whetstone, Ph.D.
Special Assistant, Research and Development
Shell Chemical Co.
Frederick W. Whittemore, Ph. D.
Acting Director of Operations Division
Office of Pesticide Programs
Environmental Protection Agency
Colin Brian Williams, Ph. D.
Program Manager
Intelcom Rad Tech
G. PhilWillsey
Director, Mountain View Research Center
Stauffer Chemical Co.
Gunter Zwelg, Ph. D.
Chief, Chemistry Branch
Office of Pesticide Programs
Environmental Protection Agency
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