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OCR for page 249
E
Survey of Pesticide R&D Directors: How Do
Current Laws Affect Agricultural Pesticide
Research Productivity?
Twenty research directors of major pesticide manufacturers partici-
pated in the survey below. All are involved in investment planning to
accommodate changes in EPA and other regulations. Survey responses
are in boxes.
I. Assume your company has a new product under development which
produced an undisputed oncogenic response (statistically significant
increase in the usual tumors seen in rat or mouse control popula-
tions), and the use pattern results in residues in processed products
which require a section 409 (food additive) tolerance.
A. What would be the percent reductions in R&D cost (direct and
administrative) to obtain a tolerance if the Delaney Clause was
not applicable, e.g., such tolerances could be granted on the
basis of a benefit/risk analysis as is done for setting 408 (raw
agricultural commodity) tolerances?
Answers varied from O to 25 percent, but most responses were in the
5-15 percent range. Two remarks suggested the same studies are
needed in either case, whereas one remark suggested oncogenicity
tests need to be repeated.
B. What is the probability of receiving a tolerance if:
(1) the current law remains as is?
249
OCR for page 250
250 APPENDIX E
(2) the Delaney Clause was not applicable?
(1) Most respondents agreed the chances would be practically nonex-
istent.
(2) The majority of respondents agreed that the probability in the
absence of the Delaney Clause would be 50 percent or greater.
C. What reduction in time delays from product discovery to final
registration would occur if Delaney was not applicable?
(months)
Answers varied from 0 to 48 months on this question, but there was l
general agreement in the range of 12-24 months. l
II. With regard to oncogenicity testing requirements that the entire
industry must complete under the reregistration process:
A. What percent of your currently registered product line do you
estimate will trigger Delaney?
Most answers to this question were in the 10-20 percent range, but six
companies responded with answers of 35 percent or above. There were
also three companies who felt Delaney would not be triggered for any
of their reregistration compounds.
B. What percent of the market for your products will be lost
because of application of Delaney?
Answers to this question were consistently in the 5-20 percent range.
One company, however, correctly observed that the agency has not yet
used Delaney in the reregistration process.
C. What percent of your currently registered products in each class
do you feel will be impacted substantially by Delaney (greater
than 10% of sales)?
insecticides
fungicides
herbicides
other
General feelings were that currently registered fungicides would be
affected significantly by the Delaney Clause with answers (when not
zero) at 50 percent or greater. Insecticides were the next most likely to
be affected with answers in the 10-20 percent range. The responses on
OCR for page 251
SURVEY OF PESTICIDE R&D DIRECTORS 251
herbicides varied greatly with eight answers ranging from 10 to 80
percent. There was an insignificant number of responses under the
"other" category. There were 60 zero or blank answers out of a
possible 80 answers to this question. The blank answers might mean
the company has no reregistration candidates in the class, and the
zeros could indicate either a certainty that none would be affected or
that the EPA would not apply the Delaney Clause to cancel tolerances
during the reregistration process.
D. In terms of lost products and lack of substitute pesticides or
other control practices, which two or three crops do you believe
will be most significantly impacted by Delaney?
The crops cited most frequently were citrus, apples, tomatoes, grapes,
corn, soybeans, cotton, and small grains.
III. A. Has the Delaney Clause ever been used by the EPA to deny the
granting of a tolerance on a raw agricultural commodity (408)
which did not involve the need for a food additive (409)
tolerance?
All answers were negative.
B. If the Delaney Clause could be cited against one of your
products to deny the granting of a necessary food additive
tolerance (409), would you:
(1) Abandon the pursuit of the tolerance?
(2) Investigate changes in use pattern to eliminate the residue
on the crop?
(31.0ther (please specify)
(4) What would be the cost of whatever action you chose to
take? Specify action
lost sales
months delay
direct testing cost
(1) Only four companies answered this question with an unqualified
yes. Three were ambivalent and the remainder said no.
OCR for page 252
252 APPENDIX E
(2) With two exceptions, all companies said yes to this question. This
indicates that attempts to change use patterns as a means of
avoiding a Delaney Clause issue is or could be a routine or common
approach in seeking a section 409 tolerance.
(3) Most companies did not respond to this part, but two companies
indicated they would examine the risk/benefit aspects of the
situation and a third indicated it would attempt to argue on the basis
of the FDA de minimus, sensitivity of the method (SOM), or
constituents policy loopholes.
(4) There was no consensus on lost sales. More than half the respon-
dents did not answer. The responses of those who did answer
varied from $0.25MM to $50MM. The delay estimates varied from
one year at a minimum to a three-year maximum with two years
about average. The direct testing cost ranged from $200M to
$500M.
C. To your knowledge, has the EPA granted food additive toler-
ances for compounds when there is clear evidence that the
tumor of concern is benign rather than malignant?
No evidence was cited that a tolerance was granted under these
conditions, but one company reminded the committee that the EPA has
not used Delaney in the reregistration process.
D. Are food processing studies for determining the declining/
increasing concentration of pesticide residues part of your
company's usual battery of tests for a new food use pesticide?
If yes, what are the typical costs of such studies per product?
Where are these processing studies done?
Internal_ Universities Food processing companies-
Eighteen of 20 companies answered yes to this question, with costs in
the $25M-$50M range for each crop processed. Most of the companies
used all three sources for doing these studies, but the university and
food processing companies were named more frequently than internal
studies.
IV. Concerns have been raised that Delaney will prevent registration of
new and/or old products for minor crops and pests.
OCR for page 253
SURVEY OF PESTICIDE R&D DIRECTORS 253
Do you view this concern as major? average? minimal?
Eleven of the respondents viewed the impact of Delaney on minor
crops as major and an additional five felt the impact would be average.
It might be concluded, therefore, that the burden on JR-4 (see Chapter
6) may be significantly increased in the future. Incentives for compa-
nies to seek minor-use registrations must also be addressed.
V. Given that our knowledge of oncogenic responses in laboratory
animals and methods of risk assessment have advanced since the
Delaney Clause became part of the Food, Drug and Cosmetic Act,
what options would you favor for its modification (please rank in
order of preference)?
A. Status quo
B. Repeal with no substitute language make section 409 track
section 408.
C. Apply Delaney to section 408—make 408 track section 409.
D. Repeal with substitute language stating approval of 409's for
oncogenic substances based on benefit/risk considerations.
E. D., but specific risk criteria.
F. An amendment stating the Delaney Clause is not applicable to
pesticides when they are not intentionally added to processed
foods or animal feed.
G. Amendment of section 409 to state that pesticides not intention-
ally added to processed foods or animal feed are not subject to
the 409 provisions.
H. Other (please specify)
It is difficult to summarize the responses to this question since the
responses varied widely. Some statements can be made, however:
· No company rated the status quo higher than 5 and most rated
this choice as 6 or 7.
· Making section 409 track section 408 was a popular choice (3 or
higher) with nine companies.
· Applying Delaney to section 408 was rated no higher than 7 by
any respondent.
· Repeal with substitute language was rated no lower than 3 by
any company with most answers being either I or 2.
OCR for page 254
254 APPENDIX E
· The application of specific risk criteria was rated from I to 6
with no consensus at all.
· The amendment stating Delaney is not applicable to pesticides
when not added deliberately to food received a lot of support but
there were also six companies who rated it 4 or below.
· Similarly, the amendment stating that pesticides not added
intentionally to processed foods or animal feeds are not subject to
section 409 provisions received mixed responses with seven an-
swers 3 or higher and nine answers 4 or lower.
· Most companies (16) did not respond to other, but one response
suggested that the definition of oncogen be sharpened so that only a
clearly oncogenic substance (multiple species, metastasis, etc.)
would trigger Delaney. The sensitivity of the method should also be
considered since zero residue is approachable but not attainable.
VI. A. How would your company's total discovery activities change (%
increase or decrease) if:
(1) 408 with specified risk criteria replaced 409 with Delaney?
(2) 408 with benefit-risk criteria replaced 409 with Delaney?
(3) Delaney also applied to 408?
(1) A few companies felt their discovery activities would increase, but
most believed the replacement would have no impact.
(2) Similarly, a few companies felt discovery activities would increase
5-30 percent but most said no impact.
(3) About a fourth of the respondents felt no change would take place;
most companies said that if Delaney was applied to section 408,
discovery activities would decrease, with those listing percentages
ranging from a decrease of 35 to 100 percent.
This response when compared with question II C indicates that
possibly companies whose products are dominated by fungicide and
herbicide products would anticipate the greatest decrease in discovery
activities.
B. List any other regulatory components you consider to be more
restrictive than Delaney for your company (e.g., drinking water,
mutagenicity, special review, teratology, reproductive effects,
etc.~.
(1) In the past.
(2) In the future.
OCR for page 255
SURVEY OF PESTICIDE R&D DIRECTORS 255
Special review, teratology, and reproductive effects were mentioned
most frequently (by about half) as being more restrictive in the past,
and groundwater and/or drinking water restrictions were listed by over
half of the respondents as being more restrictive than Delaney in the
future. This may indicate that Delaney is one of the most restrictive
regulatory components but is not alone in its restrictive impact on
companies.
C. Would your company abandon development of a promising new
active ingredient if it tested positive in:
One mutagenic end point?
Two mutagenic end points?
Three mutagenic end points?
One positive mutagenic result would cause no company to abandon
development. Two mutagenic end points yielded only five yes or
"possible" yes and 12 definite no answers. Three positive mutagenic
end points, however, prompted 14 of the respondents to answer yes
with only a few caveats.
VII. Your company's approximate pesticides sales. Check one:
Less than $100 million
More than $400 million
$100-$400 million
There were no obvious trends in the replies as a function of company
size. It is possible to conclude, therefore, that issues such as impact on
discovery activities, testing methodologies, approaches (for example,
changing use patterns in order to acquire tolerances) may be equally
significant.
Among the respondents, five companies have <$100MM in sales, nine
have between $100MM and $400MM, and six have >$400MM.
OCR for page 256
Representative terms from entire chapter:
discovery activities
