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OCR for page 136
6
Pesticide Innovation and the
Economic Effects of Implementing
the Delaney Clause
The economic effects in the agricultural sector of regulatory actions
taken pursuant to the Delaney Clause will depend on a number of factors.
These include the availability of effective currently registered alternative
chemicals and the extent and success of chemical and nonchemical new
product innovation in pest control. This chapter examines the innovation
process and seeks to determine whether the Delaney Clause has had or
will have an impact on it. This chapter also assesses the status of pest
control innovation in major areas such as plant breeding, genetic engi-
neering, and biological, cultural, and chemical pest control.
As seen in Chapter 3, the committee's estimated current level of
oncogenic risk is largely associated with old pesticides. Nearly all
estimated herbicide and fungicide risk and more than half of the estimated
insecticide risk are from pre-1978 products. If the Delaney Clause were
applied to existing tolerances for currently registered, potentially
oncogenic active ingredients, food tolerances for many economically
valuable pesticides would be lost. The resulting void would create
significant market opportunities for new non-oncogenic pesticides and
other pest control technologies. The predictable losses in company
income, however, might discourage overall investment in pesticide inno-
vation research.
Chapters 4 and 5 discuss four scenarios and tolerance reduction
approaches that the EPA might follow in regulating oncogenic pesticides.
Each scenario would require the revocation of many tolerances for
fungicides. Herbicides and insecticides would be affected to a lesser
136
OCR for page 137
PESTICIDE INNOVATION
137
extent. The two chapters focus on the short-term effects of the scenarios;
this chapter examines the scenarios' long-term effects on pest control
innovation.
It is difficult to determine whether pest control R&D efforts are
designed to eliminate oncogenic pesticide residues from the food supply.
It is even harder to determine whether the Delaney Clause is causing the
development of less-oncogenic or non-oncogenic pesticides. Experience
from past changes in EPA policies provides some insight, but there have
been few changes in federal regulation of cancer-causing agents. This lack
of data prevents studies that attempt to correlate pesticide R&D invest-
ments with different regulations on exposure to oncogens.
Another important issue is the possible effects of rapid pesticide
cancellations on R&D. In the past, single compounds have been canceled.
There are no data on the effects of the few pesticide cancellations on total
R&D activity. To gain information, the committee questioned industry
research directors, reviewed available studies on the impacts of EPA
pesticide regulations and FDA drug regulations, compiled information
from various sources on past levels and rates of pesticide innovation, and
analyzed other innovation indicators such as the number of new pesti-
cides for certain crops field tested recently.
THE INNOVATION PROCESS AND THE PESTICIDE INDUSTRY
The pesticide innovation process involves finding and developing new
compounds that are effective and safe, improving formulations of older
compounds, expanding uses of older compounds to more crops and pests,
and satisfying regulatory data requirements. The pesticide innovation
cycle goes beyond industry's discovery of new compounds. It includes
the government's approval or acceptance of product registrations, grower
awareness and adoption of new products, and long-term product viability.
The last two phases depend on a new pesticide's profitability, successful
integration with other farming practices, availability for minor crop use,
and susceptibility to pest resistance.
The development of a new pesticide is a long and expensive process.
The sequence of activities is shown in Figure 6-1. Usually 9 to 10 years
will elapse from discovery to first registration. After registration, the
market life for different pesticides varies greatly. Many pesticides widely
used today, such as 2,4-D, parathion, and the ethylenebisdithiocarbamate
(EBDC) fungicides, have been on the market for 35 years or more. But
products may lose their market share and be removed from the market for
many reasons. These include regulatory restrictions triggered by safety
concerns; competition with more active, lower-cost pesticides or
nonchemical pest controls; crop acreage adjustments; or pest resistance.
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~38 REGULATING PESTICIDES IN FOOD
-2 -1 0 1 2 3 4 5 6 7 8 9 10 11 YEARS
-1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
(9 TARGET
|~ SYNTHESIS
1---- (hi) BIOLOGICAL EVALUATION (PATENT APPLICATION)
~ ____ ~ RESEARCH FIELD USE
O I I ~ _____ (a) FORMULATION
I W PRODUCT DEVELOPMENT
FIELD TESTS
O (a) COMMERCIALIZATION DECISION
I -- - - 08) PLANT AND ANIMAL METABOLISM STUDIES
I ~ ENVIRONMENTAL CHEMISTRY BODIES
I ma) RESIDUE STUDIES
I . 1 (3 TOXICOLOGY STUDIES
COMPOUND MANUFACTURE
PROCESS CHEMISTRY ~ ----
(g) PESTICIDE TOLERANCE O
PETITION APPLICATION
am) EPA REVIEW I 1 _]
@} EPA-ACCEP I ED LABEL I
@) MARKETING--SALES I
ENVIRONMENTAL EFFECTS I 1-- - ---- -- - - --- -
OF PRODUCTION
ma) ENGINEERING DESIGN I I
em) MANUFACTURING PLANT CONSTRUCTION r I
FIGURE 6-1 Pesticide development from production to commercialization.
Source: Sharp, D. 1986. Metabolism of Pesticides An Industry View. Paper
presented at the Sixth International Congress of Pesticide Chemists, Ottawa,
Canada, August 10-15, 1986.
Many of the organochlorine insecticides have been replaced for one or
more of these reasons.
Besides the variability of a product's market life, economic returns
from a pesticide company's R&D investments can be greatly affected by
the uncertainty in the process of actually finding new pesticides. For
certain pesticides, particularly insecticides, it is increasingly difficult to
find new, effective products through conventional screening of available
chemicals. About 23,000 new compounds are now screened for each new
pesticide discovered; 10 years ago the figure was 10,000.i
It is not surprising that the pesticide industry devotes large sums of
money to research. Multinational agrichemical companies spend from 9 to
15 percent of sales revenue on R&D.2 Most R&D in pesticide and
pharmaceutical companies is internally financed and conducted. Other-
wise, the company's proprietary information may be leaked. The
OCR for page 139
PESTICIDE INNOVATION 139
drawback with internal financing is that if products are unexpectedly
canceled, funds available for R&D may shrink.
REVIEW OF INDUSTRY R&D AND STUDIES TO DATE
Although there have been no studies of how regulatory attempts to
control carcinogens may affect pesticide innovation, there have been
studies on how other EPA pesticide restrictions affect the total level and
nature of R&D efforts.
The committee examined four major studies in this area: (1) a 1981
study by the Council on Agricultural Science and Technology (CAST); (2)
a 1981 report by the Office of Technology Assessment (OTA); (3) a 1982
Ph.D. thesis by U. Hatch; and (4) a 1984 study by H. G. Grawbowski and
W. K. Viscusi.
The four studies indicate how regulatory delay and uncertainty affect
R&D activities. The CAST study found that from 1968 to 1978, direct
costs of bringing a new pesticide to market increased; delays from
discovery to first registration grew; and R&D expenditures shifted from
synthesis, screening, and field testing to registration, environmental
testing, and residue analysis.3
The OTA report emphasized that total pesticide R&D expenditures
continued to rise following the 1972 amendments to the Federal Insecti-
cide, Fungicide and Rodenticide Act (FIFRA). The increase in real R&D
investments did not cause more new pesticide registrations, however.4
Hatch attempted to quantify the relationships among the following
factors: delay from discovery to registration, FIFRA changes, and the
number of new active ingredients registered per million dollars of R&D
expenditures from 1967 to 1982. Total R&D expenditures and R&D
expenditures allocated to new chemical discoveries were used for esti-
mates. The estimated impact from a in percent longer delay in registration
was a 7 to 9 percent decrease in products registered. The creation of the
EPA in 1970 and the 1978 amendments to FIFRA seemed to have no
effects on R&D productivity.5
Grawbowski and Viscusi showed that from 1971 to 1975, R&D allot-
ments declined when compared to sales. These figures might have
reflected rapidly rising pesticide sales rather than a reduction in invest-
ments in response to the EPA's early activities. Grawbowski and Viscusi
also showed that the effective patent life for commercial pesticides fell
from 15 years during 1971 to 1976 to 12 years during 1977 to 1982. They
suggested that the delay in commercialization might redect the longer
time needed to develop new products or meet regulatory requirements for
new technology compared with the regulation of variants of established
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140 REGULATING PESTICIDES IN FOOD
products.6 A related study on the pharmaceutical industry by Graw-
bowski and Vernon found that stricter regulations induced innovation
only in techniques for complying with regulatory requirements, such as
improved equipment for detecting drug residues.7 This indicates that the
implementation of the Delaney Clause might not lead to development of
non-oncogenic pest control methods.
The committee also addressed the extent to which unexpected product
cancellations might reduce R&D investments. The regulatory scenarios
examined in Chapter 4 contemplate tolerance revocation for existing
product uses. Increased uncertainty of pesticide profits would reduce
pesticide investments. Cancellations of existing uses of some pesticides
could increase R&D investments only if they provided new sales oppor-
tunities for other pesticides and did not severely limit funds for internally
financed reinvestment. Profit opportunities from cancellation of a
competitor's products are affected by the availability of alternative pest
controls and adjustments in crop patterns.
Survey of R&D Directors
The committee questioned the research directors of 20 pesticide compa-
nies. These directors are involved in planning investment responses to
changes in regulations by the EPA and other federal agencies. They want
a regulatory environment that will give farmers and consumers confidence
that pesticide products and food are safe. They also want to sell their
products. Thus, their responses may reflect a wish to reduce regulatory
impacts. A few summaries of results from the survey are described here.
The complete survey and results are presented in Appendix E.
Asked how many pesticides would be vulnerable to Delaney Clause
restrictions during reregistration (assuming the EPA's current policies
continue), the research directors responded that 24 percent of currently
registered pesticides representing about 9 percent of total sales are in
jeopardy. About half of the fungicides and 10 to 20 percent of the
insecticides were cited as vulnerable. In addition to the loss of products,
the research directors thought there would be a slight increase in testing
costs (5 to 15 percent). More than half said that the EPA's implementation
of the Delaney Clause had caused a one- to two-year delay in new product
registrations. Companies often respond to a potential denial of registra-
tions by attempting to change use patterns to reduce residues. They may
not discontinue research or registration efforts for a potential new
pesticide if initial testing indicates one with weak oncogenicity. The
research directors viewed the Delaney Clause as an important regulation.
They identified other problems such as groundwater contamination as
more serious, however.
OCR for page 141
PESTICIDE INNOVA TION ~ 4 ~
Historical Perspective of R&D
A pesticide firm needs a dynamic R&D program if it is to remain
competitive. As shown in Table 6-1, total deflated expenditures on R&D
have risen steadily during the last 20 years. In 1985, about 64 percent of
all expenditures on pesticide R&D in the United States were for discov-
ering and developing new products, 23 percent for expanding uses of
existing products, and 13 percent for defending older products.8 Industry
experienced an increase of 14.4 percent for R&D expenditures in 1985
compared with 6 percent in 1983 (Table 6-11. This was in the face of a 9
percent drop in domestic pesticide sales between 1984 and 1985.
Most pesticide R&D in the United States takes place at about 20
multinational corporations that manufacture active ingredients for pesti-
cides. Hundreds of middle-sized and small companies develop, produce,
TABLE 6-1 Pesticide Industry Total R&D Expenditures
Annual
Undeflated Deflateda Increase
Year (millions of dollars) (millions of dollars) Deflated (%)
1967 $ 52.4 $ 65.9
1968 58.2 70.6 7.1
1969 64.1 73.8 4.5
1970 69.9 76.4 3.5
1971 87.7 91.4 19.6
1972 98.5 98.5 7.8
1973 110.7 104.7 6.3
1974 134.8 117.1 11.8
1975 160.5 127.6 9.0
1976 195.2 147.5 15.6
1977 250.1 178.5 21.0
1978 289.6 192.5 7.8
1979 332.3 203.3 5.6
1980 395.1 221.2 8.8
1981 449.9 230.1 4.0
1982 526.9 254.3 10.5
1983 580.2 269.5 6.0
1984 730.6 327.0 21.3
1985 868.9 374.2 14.4
Average 10.2
aThis column expresses deflation by the GNP deflator (1972 = 100).
SOURCE: Hatch U., 1983, The Impact of Regulatory Delay on R&D Productivity and
Costs in the Pesticide Industry, Ph.D. dissertation, University of Minnesota, St. Paul;
National Agricultural Chemical Association, 1986, Industry Profile Survey: 1985, Wash-
ington, D.C. Photocopy.
OCR for page 142
142 REGULATING PESTICIDES IN FOOD
and blend thousands of pesticide mixtures and retail products, but they
conduct little research to develop new active ingredients. Smaller firms
conduct more R&D in biological and genetically engineered pest control,
however.9
Long- and short-term innovation prospects are important in assessing
Delaney Clause implications. As discussed previously, the EPA schedule
of pesticide reregistrations will require decisions in the next three to five
years on many products that currently have large sales. This places an
emphasis on pesticide development and marketing pesticides that have
already entered field testing. Compounds being developed have the
potential to lessen short-term effects of pesticide use cancellations. The
next 9 to 10 years will probably be the shortest feasible time to bring new
pesticide chemistry or biotechnology products to market. It will be even
longer before the products are widely adopted by farmers.
One indication of innovation's rate and trend is the number of pesti-
cides registered for the first time each year. This information for the past
20 years is shown in Table 6-2. (Only about two-thirds of these pesticides
have agricultural uses.) Overall, the introduction of products for agricul-
tural use decreased, even though firms submitted 25 new pesticide
compounds for registration in 1985, which was 10 more than in 1984.
Some promising new herbicides were also registered for use in 1986.
However, new products must compete with the performance of and
farmers' loyalties to existing products. As a result there are considerable
differences in the adoption and sales of new products compared with older
ones.
INSECTICIDES
.
In the last 40 years, the major three classes of pesticides insecti-
cides, herbicides, and fungicides have evolved at different rates. The
chemistry of insecticide products has developed through four genera-
tions: (1) organochlorines, such as DDT, chlordane, aldrin, and dieldrin;
(2) organophosphates, such as parathion; (3) carbamates, such as
carbaryl and carbofuran; and (4) pyrethroids, including permethrin and
cypermethrin. Changes in use patterns were influenced by acute and
chronic toxicity, environmental effects, and insect resistance to widely
used compounds.
Regulatory actions based on chronic health and environmental effects
have largely eliminated all uses of organochlorine insecticides on foods.
Organophosphate and carbamate insecticides remain widely used; syn-
thetic pyrethroids continue to gain market share. Pest resistance, how-
ever, has become a limiting factor in the success of chemical insecticides.
Synthetic pyrethroids were widely considered a breakthrough when
OCR for page 143
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OCR for page 144
~44 REGULATING PESTICIDES IN FOOD
introduced in the 1970s. But the emergence of resistance of some pests to
pyrethroids in some areas is worrisome. In particular, pockets of resis-
tance to pyrethroids by the tobacco budworm have been shown in
cotton-producting areas of Texas. Since the pyrethroids, no new major
chemical class of insecticide has been commercialized. Several new
classes of insecticide show promise for a wide range of agricultural and
public health uses, but there are no new classes of proven materials for
control of the budworm and the bollworm.
HERBICIDES
The invention of new herbicides has flourished during the past 40 years
with the development and wide acceptance of many different chemical
classes. These include phenoxy herbicides, such as 2,4-D; triazines, such
as atrazine and cyanazine; benzoic acids, such as dicamba; acetanilides,
such as alachlor and metolachlor; ureas, such as linuron; and the
nonselective, broad-spectrum glyphosate. In the past few years, the
number of newly registered herbicides introduced into the market sub-
stantially surpassed the number of new agents in all other major catego-
ries of pesticides combined.
Several new herbicides were registered in 1986. These compounds
represent the first marketable results of resew herbicide chemistry. The two
most important classes of new herbicides are the imidazolinones and the
sulfonylureas. Tests show that these herbicides are non-oncogenic. They
are generally applied at rates lower than the herbicides in wide use today.
The principal factor behind the success in chemical herbicide innova-
tion is the size of the herbicide market. Agricultural herbicide sales in the
United States are about $2.7 billion. This is about two and one-half times
the size of the domestic insecticide market and about 10 times greater
than the fungicide market.
As discussed previously, some of the widely used herbicides are
suspected or confirmed animal oncogens. Oncogenic herbicides account
for about 60 percent of current expenditures for chemical weed control
(see Chapter 31. Possible regulatory actions restricting the use of these
herbicides could create opportunities for new herbicides or other weed
control methods.
FUNGICIDES
The unique case of fungicides has been discussed at length in Chapters
3-5. Fungicides registered in the 1940s and 1950s currently dominate the
market because they are relatively inexpensive, effective against a broad
OCR for page 145
PESTICIDE INNOVATION 145
range of pathogens, less prone to pest resistance problems, and exhibit
low acute toxicity. In addition, they are often important in integrated
disease management programs. These factors give existing products a
formidable competitive edge over new fungicidal compounds. Yet, it is in
dealing with fungicides that a strict application of the Delaney Clause may
most significantly affect current product use.
Ninety percent of all fungicide acre treatments are with potential animal
oncogens. Furthermore, chronic toxicity to humans is likely to remain a
problem because it is difficult to develop fungicides that are not toxic to
genetic material. As a result, the fungicides, and growers who rely heavily
on them, are particularly vulnerable to actions to restrict dietary exposure
to potential oncogenic compounds. To aggravate this problem, the
science involved in producing new fungicides is extremely complex, and
developments in recent years have been minor.~° For example, in the past
15 years, only four new fungicides have been introduced that account for
more than 5 percent of sales in any food crop. This is not because
fungicide research and development expenditures have lagged. These
investments are nearly twice as high relative to sales as are investments
for herbicides and insecticides. Because total fungicide sales are rela-
tively small, however, total fungicide research is modest. Also, because
individual fungicide markets are small, there is less economic incentive
for innovation and product expansion. Further, the development of
products for minor crops is not often profitable for pesticide companies.
(The influence of market size on pesticide registration is discussed at
greater length later in this chapter.) Some new product work in Europe
has been directed toward combinations of old and new fungicides.
FUTURE PROSPECTS IN CHEMICAL PEST CONTROL
It is difficult to obtain an accurate count of the pesticides for which new
registrations are being sought that will become available for commercial
use. Using the number of tolerance petitions for this purpose can be
misleading because the percentage of petitions for new active ingredient
tolerances not granted is unknown.
Because of these uncertainties, the committee obtained information
from specialists in crop protection and published reports of field tests to
learn which unregistered pesticides are now being field tested. The
inquiry concentrated on the production of selected crops that might be
affected by the cancellation of currently marketed pesticides. Some of the
pesticides being reviewed are already registered for use on other crops;
others have no current registration. The results help clarify which
compounds are being developed and provide some indication of chemical
substitution possibilities in the next five years.
OCR for page 146
|46 REGULATING PESTICIDES IN FOOD
TABLE 6-3 Evaluation of Experimental and Unregistered Citrus
Insecticides
Comparison to Best
Commercially Available Standard
Target Pest
Number of
Compounds Better Similar Poorer
Thrips
Compounds near registration 4
Compounds under evaluation 6
Red mite
California red scale
10
4
0 1 3
0 0 6
3a
0 0 4
NOTE: A total of 19 insecticides were tested by insecticide and acar~cide tests.
aEvaluations for only 3 of the 10 materials were adequate to provide a comparison to
commercial standards. The remaining 7 need additional testing.
SOURCE: York, Alan C., ed. 1985. Insecticide and Acaracide Tests. Vol. 10. College
Park, Md.: Entomological Society of America.
Citrus and Cotton Insecticides
The committee's findings for the citrus insecticides are presented in
Table 6-3. Except for three products to control red mites and one to
control thrips, the compounds being tested were judged less effective than
currently available insecticides and acaricides.
Thirteen unregistered cotton insecticides were evaluated and reported
in Insecticide and Acaricide Tests. Some were tested on more than one
pest. Eight new materials were tested on bollworms, eight on boll
weevils, two on cotton heahoppers, one on cotton aphids, and six on
spider mites. Variability in results precluded a valid comparison with the
best commercially available insecticides.
Cotton pest control research is inspired more by potential pest resis-
tance than by the Delaney Clause. Currently available non-oncogenic
cotton insecticides and integrated pest management programs appear
adequate to sustain the U.S. cotton industry.
Corn and Soybean Herbicides
Several products representing new chemistry (most notably the
imidazolinone and sulfonylurea compounds) have been commercially
introduced in the past several years. Manufacturers now are more
sophisticated in designing new molecules with herbicidal activity. Be-
cause one or more functional groups of chemicals are known to affect
OCR for page 150
150 REGULATING PESTICIDES IN FOOD
70
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HERBICIDES
FIGURE 6-2 Estimated dietary oncogenic risk and R&D expenditures by
pesticide type.
· Increasing costs for required test data to support tolerances for
registration or reregistration;
· Shortening the commercial lives of pesticides through tolerance
revocations or product cancellations;
· Increasing the borrowing costs when tests and other procedures
prolong the time from discovery to marketing; and
· Increasing net return variability and thereby discouraging investment
because of uncertainty about EPA implementation strategies.
INNOVATION PROSPECTS IN PEST CONTROL
Plant Breeding
Although plant breeding for resistance to pests began in the late
nineteenth century, the development of crop varieties resistant to insect
pests was not pursued energetically until recently. This lack of interest
was primarily because resistance was difficult to achieve, and other
low-cost, effective controls were often available. Nevertheless, plant
breeders have developed more than 150 cultivars with insect resistance.
The rewards of successful insect resistance research can be great. For
example, federal, state, and private agencies spent about $9.3 million on
developing resistance in wheat to the Hessian fly and wheat stem sawfly;
OCR for page 151
PESTICIDE INNOVATION ~5 ~
in alfalfa to the spotted alfalfa aphid; and in corn to the European corn
borer. Savings to farmers from resistant varieties are estimated at several
hundred million dollars annually, not including savings from eliminating
pest control chemicals. Additional examples of insect-resistant crop
cultivars include the resistance of rice to the brown planthopper, alfalfa to
the pea aphid, and sorghum to the green bug.
Breeding for resistance to plant diseases has been pursued vigorously
and to much greater advantage than for resistance to insects. This is in
spite of the fact that some cultivars can resist only a few diseases, which
enhances the possibility of an epidemic, such as the southern corn leaf
blight in 1970. Resistant cultivars of cereal crops have been the mainstay
of disease protection for many years. Success in crop breeding includes
disease resistance of corn to southern corn leaf blight and other blights,
wheat to stem rust, cucurbits to powdery mildew, cotton to Fusarium
wilt, alfalfa to bacterial wilt, pears to fire blight, tobacco to bacterial wilt,
and sugarcane to mosaic disease. Resistant cultivars have also been the
major means of controlling parasitic nematodes, especially some species
of root-knot, cyst-causing, and stem nematodes.
Some plants naturally produce chemicals that protect them against
weeds and other pests. Cultivars are being developed that have traits for
producing metabolites that are toxic to specific weeds, fungi, insects, or
even grazing animals. For example, chemicals from the wild Bolivian
potato have been correlated with its resistance to insect pests that attack
potatoes cultivated in the United States. Scientists are working to breed
these traits into U.S. potato varieties.
But, resistant cultivars do not necessarily stay resistant. Depending on
crop management and biological factors, mutant organisms frequently
develop. Therefore, different types of resistance must be incorporated
into cultivars. Breeding for resistance requires no more time than the
development of a new pesticide, and the expenditures of time and
resources have been well worth it in many cases.
Genetic Engineering
Specific genetic characteristics can be manipulated in microbes and
plants to achieve crop protection. (For an in-depth discussion, see
Agricultural Biotechnology: Strategies for National Competitiveness. ]2)
Genetic engineering could increase the potential for effective insect
control via modification of bacteria, viruses, and fungi. For example,
bacteria and viruses infecting insects could be genetically engineered to
produce toxins that only kill specific insects. A possible candidate is
the baculovirus, which infects only specific pests and is harmless to
OCR for page 152
152 REGULATING PESTICIDES IN FOOD
beneficial insects, vertebrates, and plants. However, development prob-
lems exist with baculoviruses, including the need to expand the range of
particular viruses to encompass more than one pest species, the need to
improve their environmental stability, and the facilitation of their large-
scale commercial production.
Fungi also might be engineered as safe, effective insect and weed
control agents. Many fungi produce specific toxins that act against insects
or plants. Their "toxin" genes could be enhanced and transferred to new
fungal hosts to create biological control agents that would attack only
specific insects or weeds.
Plants themselves can be targets of genetic engineering. A crop can be
genetically altered to express a specific, limited portion of a plant virus's
genetic information, which would give the crop resistance to infection by
that virus. Scientists have already achieved plant resistance to the
tobacco mosaic virus, which causes large commercial losses of tomatoes
and bell peppers as well as tobacco.
In a related strategy, the gene responsible for a plant's natural resis-
tance to certain pathogens can often be transferred to a susceptible
cultivar which might differ only by that single "resistance" gene.
Alternatively, the pathogen or its toxin can be used in the laboratory to
select resistant cultivars from cell cultures. Intensive investigation on this
front has led to isolation of some disease-resistant plants.
Research on herbicide-resistant crops is in progress. Resistant
cultivars can be selected from cell cultures, a strategy that has been used
to select imidazolinone-resistant corn. "Resistance" genes from other
plants or even bacteria can be genetically engineered; glyphosate-
resistant plants have been created by this technique. And, the two
techniques are being combined to create crops resistant to sulfonylurea
herbicides.
Fruit and vegetable seed markets, because they are small, will not
stimulate rapid development of biotechnology products. Developments in
pest control for minor crops from genetic engineering and conventional
plant breeding are not likely to come soon enough to replace the many
potential pesticide use cancellations in the next three to five years. Private
genetic engineering firms will probably produce animal drugs and
herbicide-resistant cultivars of major crops rather than alternative pest
controls for those canceled by the Delaney Clause. Legal and regulatory
issues have significantly curtailed development and testing of genetically
engineered biological control agents. Until these issues are resolved, the
benefits that these agents could provide will not be available to farmers in
this country.
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PES TI CIDE INNO VA TI ON 1 5 3
Biological Control
Biological control is the regulation of pest populations by natural
enemies. In this report, biological pest control involves the intentional
release or introduction of any biological organism, such as viruses,
predators, pathogens, and parasites.
In the United States, biological control currently plays a limited but
significant role in agriculture. In certain crops in some regions, biological
control strategies are critical to continued production of important cash
commodities. In many cases biological control methods have been
integrated with selective use of chemical pesticides. For example, the
release and establishment of predatory mites biologically controls spider
mites on almonds in some areas of California. The predatory mites were
selected in the laboratory for resistance to insecticides commonly used in
almond production. This program has reduced the need to apply acaricide
sprays and is less costly than total reliance on chemical pest control.
Compared with synthetic chemical pesticides, however, biological
controls are applied against relatively few economically important agri-
, , _'
. em. . . · . ~ . · . · . , , . . .
~ ·~
cultural nests. The potential tor biological pest control has been s~gn~-
cant for specific pests, as evidenced by valuable programs for certain
crops. The development of biological control agents and systems is
limited by the following factors:
· The implementation and maintenance of effective management prac-
tices. Biological control is complex compared with chemical spray
treatments, schedules, and practices.
· The specificity of biological control organisms. Although some
organisms may control a few pest species, usually a unique biological
control is needed for each pest.
· The mobility of certain control organisms. This factor may lead to
free benefits for some farmers from pest control paid for by other
growers. ~3
Biological systems to manage insect pests have been established in
several crops, most notably citrus, nuts, and apples. In addition, biolog-
ical insect control agents are used as components of integrated pest
control in cotton, citrus, rice, nuts, soybeans, fruits, vegetables, and
deciduous fruit crops.
Several biological compounds are now registered or being considered
for registration to control various insect pests. The use of Bacillus
thuringiensis to control lepidopteran larvae is widespread. A few bacterial
compounds are near final registration; among them are Trichoderma for
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~54 REGULATING PESTICIDES IN FOOD
the control of Armillaria root rot and Agrobacterium radiobacter for the
control of crown gall.
Control can also be achieved by using insect pheromones, normones,
or their analogs to attract and trap pests, induce fruitless mating, or arrest
development of insect larvae. Juvenile hormones are currently registered
and sold to control flies, mosquitoes, Heas, and cockroaches. When
applied as a spray, they arrest insect development at an immature stage,
preventing reproduction as well as destructive adult-stage activities.
Although the genetically engineered Pseudomonas syringae protects
crops from frost, not disease, it is a potentially significant biological
control. Once field tests are permitted, tests with other genetically
engineered organisms are expected to follow.
Nuclear polyhedrios viruses (NPVs) are being considered for control of
a range of pests including the cotton bollworm, tussock moth, gypsy
moth, alfalfa looper, and European pine sawfly. A granulosis virus has
been identified that controls the coaling moth.
Several insecticidal fungi are in use in various countries. It is necessary
to remember, though, that some chemical fungicides kill insecticidal fungi
unless applications are timed to avoid this.
Historically, biological control of weeds has been successful only for
uncultivated areas. Recently, however, the control of several weeds in
cultivated crops by fungal pathogens has been moderately successful.
Unfortunately, the elimination of a weed species results in its replacement
by another weed that may be more or less damaging than the first.
Research on the biological control of plant diseases is increasing so
rapidly that the American Phytopathological Society will soon start
publishing a journal devoted to that topic.
Cultural Pest Control
Cultural pest control involves manipulation of the crop or soil to make
it less favorable for pests. Various cultural practices have been used since
agriculture's beginnings, and will continue to be used. The incorporation
of cultural practices into integrated pest management programs can be
expected to increase because of cost savings. These practices include
tillage, selection of a planting date to avoid a specific pest, crop rotation,
stripcropping, interplanting, and destruction of crop remains to reduce
habitats for overwintering pests. Increased emphasis is being placed on
the management of economically important pests on crops including
citrus, cotton, tomatoes, and alfalfa. Although integrated pest manage-
ment programs can be highly effective, they frequently can be profitably
applied only in limited regions. Nonetheless, in the future, more oppor-
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PESTICIDE INNOVATION 155
"unities to combine genetic, chemical, biological, and cultural control
strategies will emerge, changing the control of pests.
SPECIAL CHALLENGES TO INNOVATION
The Minor-Use Issue
Factors that determine the minor-use status of a particular crop or crop
and pest combination include gross sales from the crop's potential
pesticide market (generally a function of total crop acreage); relative
value of the crop per unit area; susceptibility of the crop to pest damage
throughout the season; and availability of nonpesticide controls.
Production of most minor crops typically requires several pesticides.
However, there is little incentive for pesticide manufacturers to pursue
registration of their products for uncommon pests and crops grown on
limited acreage except as a step in establishing a share in a larger market.
The volume of pesticides used is often so low that a manufacturer's costs
to obtain and maintain registration are not compensated by revenues from
pesticide sales. This fact has important consequences, because all vege-
table, fruit, and ornamental crops are in the minor use category. Vegeta-
bles and fruits currently constitute about 20 percent of consumer diets,
and the percentage is increasing.
Minor-use tolerances for many pesticides are not supported by studies
meeting current data requirements for oncogenicity, environmental ef-
fects, and residue chemistry. For some minor-use pesticides not regis-
tered for a major crop, particularly those no longer protected by patents,
the cost of meeting the EPA's data requirements may make it uneconomi-
cal for manufacturers to pursue reregistration. Nearly all important
minor-use pesticides are also registered for some major uses, however,
and are less likely to encounter this problem. In these cases, registration
for minor crop uses often is obtained as a label expansion after the
product generates revenue from its major crop uses.
LIABILITY
The threat of liability suits is a cost that must be considered in entering
any market. Liability for crop failures or crop injury resulting from
product use is another impediment to pesticide registration for minor crop
uses. The problem can be especially serious for many vegetable, fruit, and
ornamental crops. These crops tend to have relatively high values per
acre, have low pesticide sales potential relative to possible liabilities, and
are expected to meet high-quality standards. Even when these consider-
ations do not impede registration, if the acceptable daily intake for a
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156 REGULATING PESTICIDES IN FOOD
pesticide is used fully by other tolerances involving larger markets, the
minor-use tolerance generally will not be sought because it would
necessitate restriction of use in a larger market.
The minor-use problem is a product of the 1972 amendments to FIFRA,
which among other things made it unlawful to use any registered pesticide
in a manner inconsistent with its label. These amendments banned the
application of registered pesticides for uses not specified on the label,
which meant that each crop and pest combination had to appear on the
label. In addition to the costs of obtaining specific registrations for each
crop and pest combination, the registrant was liable for phytotoxicity and
other product-related failures.
Later amendments to FIFRA in 1978 and the EPA's announcement of
new policies in 1986 have helped to ease the minor-use problem. The
agency has announced a new definition of "use inconsistent with label-
ing," which permits application of a pesticide to control an unnamed
target pest as long as the pesticide is registered for use on the crop. The
EPA's new policies allow the agency to adjust its data demands and
registration fees for minor-use registrations in light of the anticipated
extent of use, degree of human and environmental exposure, toxicity of
the compound, volume of use, geographic distribution of potential use,
and cost of data requirements for registration.
INTERREG~oNA~ PRo~EcT 4
Another important factor in dealing with the minor-use issue is the U.S.
Department of Agriculture's Cooperative State Research Service Inter-
Regional Project 4 (IR-41. JR-4 provides a mechanism for state agricul-
tural research and extension workers to identify specific pesticides that
will meet particular needs on minor crops. These workers will be able to
cooperate with others in research and extension to develop the efficacy
and residue data necessary to obtain tolerances and secure registrations
for minor uses. In all cases, the company developing or marketing the
pesticide or a third party must agree to serve as the registrant before the
JR-4 will develop data needed to support a minor crop use registration.
Although its financial resources are limited, JR-4 efforts at the federal and
state levels can relieve companies of some of the financial burden of
obtaining minor-use tolerances. The JR-4 has helped to obtain tolerances
and registrations for pesticide uses on many minor crops, which other-
wise would not have been pursued by the pesticide companies.
Although policy changes are addressing the problem of obtaining new
pesticide registrations for minor crops, the problem of liability remains.
Also remaining is the lack of incentive for manufacturers to develop
pesticide products that have potential uses on a small number of minor
OCR for page 157
PESTICIDE INNOVATION ~57
crops and limited potential uses on any major crops. In addition, the
forthcoming reregistration of currently registered pesticides will probably
create serious new problems for some existing minor-use registrations.
The EPA has identified a substantial number of pesticides with minor-use
tolerances as animal oncogens. Some tolerances and registrations for
these pesticides will probably be lost during reregistration. The impact
will be greatest on fungicides, which are essential for commercial fruit and
vegetable production in humid production areas, and for which there are
virtually no registered alternatives. Moreover, there are few potential
replacements under investigation or development. The impact on minor-
use insecticides and herbicides is likely to be less severe.
So far the Delaney Clause has had little impact on the registration and
reregistration of minor-use pesticides. This is because the EPA has not
yet applied the clause to tolerances established before contemporary
oncogenicity data requirements were established. Only a small percent-
age of all minor crops with processed food forms are currently included in
the residue chemistry guidelines (Subsection O of the Pesticide Assess-
ment Guidelines; see Table 3-11) listing crops for which the EPA requires
processing studies or in the National Food Processors Association's list
of proposed additions to Subsection O (see Table 3-131. If the number of
minor crops listed in Subsection O is expanded, the effects of the Delaney
Clause will become proportionately larger.
The Pesticide Resistance Problem
Pesticide resistance is an increasingly serious problem. In 1984, 447
species of insects and mites, 100 species of plant pathogens, 55 species of
weeds, 2 species of nematodes, and 5 species of rodents were known to
be resistant in some location to one or more pesticides used for their
control.~4 Combining pesticides having different modes of action, reduc-
ing application frequencies, and rotating pesticide types are important
tactics of pesticide resistance management requiring the availability of
several effective pesticides. To the extent that pesticide cancellations
limit the number and spectrum of available pesticides, the crop produc-
er's ability to manage pesticide resistance will be hampered.
The problem of managing pesticide resistance is likely to be acute in the
case of fungicides, because many of the protectants in use for many years
without causing resistance are under regulatory review at the EPA. Loss
of these fungicides would lead to greater reliance on newer systemic,
site-specific, eradicant fungicides, such as metalaxyl and benomyl. The
long-term viability of relying on such fungicides is suspect, because plant
pathogens commonly develop resistance to these types of fungicides. If
the older oncogenic protectant fungicides are lost as a result of regulatory
OCR for page 158
158 REGULATING PESTICIDES IN FOOD
actions, innovation in integrated disease management will become not
only valuable but necessary.
To slow the selection of resistant pathogens, the use of site-specific
fungicides must be precisely managed. A major feature of resistance
management in crop diseases is the mixing of eradicant site-specific
fungicides with older, protectant fungicides. Such mixtures combined
with fungicide rotation help prevent resistance. Pesticide companies and
land-grant universities are developing disease resistance management
schemes to prolong the effectiveness of fungicides such as triadimenol,
metalaxyl, and benomyl, because resistance has developed in high-use
areas. Disease-resistant crop varieties are also being introduced to reduce
fungicide use and resistance. Tolerance reductions that encourage more
judicious use of protectant fungicides would enhance disease manage-
ment innovation and reduce the oncogenic risk associated with residues
of these fungicides.
NOTES
1. National Agricultural Chemicals Association. 1986. Industry Profile Survey. Washing-
ton, D.C., p. 9.
2. Ibid.
3. Council on Agricultural Science and Technology. 1981. Impact of Government Regu-
lation on the Development of Chemical Pesticides for Agriculture and Forestry. Report
- No. 87. Ames, Iowa: Council on Agricultural Science and Technology.
4. Office of Technology Assessment. 1981. Technological Innovation and Health, Safety,
and Environmental Regulation. Washington, D.C.: Office of Technology Assessment.
5. Hatch, U. 1983. The Impact of Regulatory Delay on R&D Productivity and Costs in the
Pesticide Industry. Ph.D. dissertation. University of Minnesota, St. Paul.
6. Grawbowski, H. G., and W. K. Viscusi. 1984. EPA Regulation and Pesticide Innova-
tion: An Exploratory Analysis. Washington, D.C.
7. Grawbowski, H. G., and J. M. Vernon. 1983. The Regulation of Pharmaceuticals:
Balancing the Benefits and Risks. Washington, D.C.: American Enterprise Institute.
8. National Agricultural Chemicals Association, p. 13.
9. U.S. Environmental Protection Agency. 1980. Guidelines for Contents of Economic
Impact Analysis. Washington, D.C.: U.S. Environmental Protection Agency.
10. Brent, K. J. 1985. One hundred years of fungicide use. In Fungicides for Crop
Protection: 100 Years of Progress. BCPC Monograph No. 31. Bordeaux, France.
11. York, A. C., ed. Insecticide and Acaricide Tests. 1984. Vol. 9. College Park, Md.:
Entomological Society of America.
12. National Research Council. 1987. Agricultural Biotechnology: Strategies for National
Competitiveness. Washington, D.C.: National Academy Press.
13. Reichelderfer, K. H., G. A. Carlson, and G. A. Norton. 1984. Economic Guidelines for
Crop Pest Control. Food and Agriculture Organization Plant Production and Protection
Paper No. 58. Rome: Food and Agriculture Organization.
14. National Research Council. 1986. Pesticide Resistance: Strategies and Tactics for
Management. Washington, D.C.: National Academy Press.
OCR for page 159
APPENDIXES
OCR for page 160
Representative terms from entire chapter:
delaney clause
