PB86-129426
Hazard Evaluation Division, Standard
Evaluation Procedure. Magnitude of the
Residue: Crop Field Trials
(U.S.) Environmental Protection Agency
Washington, DC
Jun 85
U.S. DEPARTMENT OF COMMERCE
National Technical Information Service
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PB86-12942b
EPA-540/9-85-021
June 1985
HAZARD EVALUATION DIVISION
STANDARD EVALUATION PROCEDURE
MAGNITUDE OF THE RESIDUE:
CROP FIELD TRIALS
Prepared by
M. J. Nelson, Ph.D.
Standard Evaluation Procedures Project Manager
Stephen L. Johnson
Hazard Evaluation Division
Office of Pesticide Programs
United States Environmental Protection Agency
Office of Pesticide Programs
Washington, D.C. 20460
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SOJ77-101
REPORT DOCUMENTATION *• REPORT NO. 2.
PAGE
4. Title end Subtitle
HAZARD EVALUATION DIVISION, STANDARD EVALUATION PROCEDURE
Magnitude of the Residue: Crop Field Trials
7. Authord) . .
M. J. Nelson
9. Performing Organization Neme ind Addreu
U.S. Environmental Protection Agency/OPP/HED/.(TS-769C)
401 M Street SW
Washington, D.C. 20460
12. Sponsoring Organisation Name and Addreu
Same as #9.
J. Recipient's Accession No.
PB8b 129 42 6 /AS
7
5. R»port Data
June 1985
0.
8. Pel tw mine* Onranlntfnn BWM* MM-
EPA-5W9-85-021
ia Prorsct/Tesk/Work Unit No.
11. ContrecttO or QnnKQ) No.
(O
(G)
IS. Typo of Report & Period Covered
14.
15. Supplementery Notes
Supplement to Pesticide Assessment Guidelines Subdivision 0: Residue Chemistry
(Eff\ 540/9-82-023 and NTIS Order Number PB83-153981), October 1982.
1C AbMract (Umlt 200 wontt)
The Standard Evaluation Procedure (SRP) for tlie Magnitude of the Residue: Crop
Field Trials is a guidance document prinviri.ly intended for Agency reviewers and' the regu-
lated industry who evaluate data .specified in 40 CFR Part 158.145. The SEP is also
intended to provide information to the generaJ. public1 indicating how the Agency evaluates
these types of studies. As such, it is designed to supplement Subdivision 0 of the
Pesticide Assessment Guidelines: . Residue Chemistrv.
17. Document Analyde e. Descriptor*
Reproduced from
best available copy.
b. Idontlften/OpertCndod Term*
e. COSAT1 Field/Group
im. Availability auuiiinH
Unclassified and
freely available.
19. Security CU*» (This Report)
Unclassified.
2O. Security Clan (TM« Page)
Unclassified .
^21. No. of Pi
"••»
vt
22. Prtea
(Sea ANSI-Z39.18)
I fWtnj Ct Jo AS OO
omoNAL mat 272 (4-77)
(Formerly NT1S-3S)
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STANDARD EVALUATION PROCEDURE
PREAMBLE
This Standard Evaluation Procedure (SEP) is one of a set of
guidance documents which explain the procedures used to evaluate
environmental and human health effects data submitted to the
Office of Pesticide Programs. The SEPs are designed to ensure
comprehensive and consistent treatment of major scientific topics
in these reviews and to provide interpretive policy guidance
where appropriate. The Standard Evaluation Procedures will be
used in conjunction with the appropriate Pesticide Assessment
Guidelines and other Agency Guidelines. While the documents were
developed to explain specifically the principles of scientific
evaluation within the Office of Pesticide Programs, they may also
be used by other offices in the Agency in the evaluation of
studies and scientific data. The Standard Evaluation Procedures
will also serve as valuable internal reference documents and will
inform the public and regulated community of important consider-
ations in the evaluation of test data for determining chemical
hazards. I believe the SEPs will improve both the quality of
science within EPA and, in conjunction with the Pesticide Assess-
ment Guidelines, will lead to more effective use of both public
and private resources.
^ .
4^
John W. Melone, Director
Hazard Evaluation Division
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TABLE OF CONTENTS
Page
I. INTRODUCTION
A. Purpose of the Standard Evaluation
Procedure 1
. B. Background Information 1
C. Objective of Crop Field Trials 1
II. INFORMATION TO BE SUPPLIED
III. THE DATA EVALUATION PROCESS
A. Prepare a Summary 2
B. Identify Data Gaps 3
C. Assess the Appropriateness and Adequacy
of the Data 3
D. Determine the Need for Deferral/Referral(s)
to Other HED Branches 3
E. Conclude if the Requested Action is
Supportable 4
IV. REVIEWER AIDS
V. APPENDICES
Appendix 1: Major Points to Consider in
Evaluating Crop Field Trial Data 5
Appendix 2: Reviewer Aids Materials 17
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MAGNITUDE OF THE RESIDUE; CROP FIELD TRIALS1'2
I. INTRODUCTION
A. Purpose of the Standard Evaluation Procedure
This Standard Evaluation Procedure is designed to aid Residue
Chemistry Branch data reviewers in their evaluations of crop
field trial studies submitted by petitioners/registrants. This
particular Standard Evaluation Procedure document addresses crop
raw agricultural commodities.1
B. Background Information
Crop field trials to provide residue chemistry data on the
magnitude of the residue are required by 40 CFR 158.125 to
support the registration of any pesticide intended for use on a
food or feed crop under the amended Federal Insecticide, Fungi-
cide, and Rodenticide Act.
Residue chemistry data on raw agricultural commodities (r.a.c.'s)
are used by the Agency to estimate the exposure of the general
population to pesticide residues in food, and for setting and
enforcing tolerances for pesticide residues in or on raw agri-
cultural foods or feeds under provisions of Section 408 of the
Federal Food, Drug, and Cosmetic Act. [Note: Processed foods
and feeds are regulated under Section 409 of the Act.]
Residue chemistry data are also needed to support the adequacy
of one or more methods for the enforcement of the tolerance,
and to support practical methods for removing residues that
exceed any proposed tolerances.
C. Objective of Crop Field Trials
Crop field trial studies should answer the following question:
What is the maximum level of "total toxic residue" that will
I/ Other aspects of the Magnitude of the Residue [see 40 CFR
158.125: processed food/feed; meat/milk/poultry/eggs;
fumigation uses; dermal uses; post-harvest treatment] will
be addressed in separate Standard Evaluation Procedure docu-
ments (to be developed in FY 85).
2/ This Standard Evaluation Procedure is to be used in conjunc-
tion with the Standard Format for Preparation of Tolerance
Petition Reviews (now under development) that describes
the content and considerations of a Residue Chemistry Branch
data review memorandum.
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likely result in or on the raw food or feed commodity- as a result
.of application of the pesticide formulated product according to
the proposed label directions for use.
The term "total toxic residue" is used to describe the sum
of the parent pesticide and its degradation products, metabolites
(free or bound), and impurities that are considered to be of
toxicological significance, and therefore warrant regulation.
II. INFORMATION TO BE SUPPLIED
The petitioner/registrant's report on crop field trials on
a raw agricultural commodity should include all information
necessary to provide a complete and accurate description of
field trial treatments and procedures; sampling (harvesting),
handling, shipping, and storage of the r.a.c.; storage stability
validation of the test chemical [and metabolite(s) of special
concern]; residue analyses of field samples for the "total
toxic residue" [and for individual components of special concern];
validation (recovery studies) of the residue analytical methodo-
logy; reporting of the data and statistical analyses; and,
quality control measures/precautions taken to ensure the fidelity
of these operations.
A guideline of specific information that should be included
in the petitioner/registrant's report of crop field trials is
provided in the Residue Chemistry Branch Data Submission Guideline
on the Magnitude of the Residue: Crop Field Trials,-^ that
complements this Standard Evaluation Procedure. Related informa-
tion on Nature of the Residue: Processed Food/Feed, Analytical
Method(s), and Storage Stability are found in the Standard
Evaluation Procedures^ and Data Submission Guidelines-^ on
those subject areas.
III. THE DATA EVALUATION PROCESS
A. Prepare a Summary
The initial step in the evaluation process of crop field
trials on a raw agricultural commodity is for the reviewer to
carefully examine and summarize the information/data supplied by
the petitioner/registrant in his submission to the Agency.
Statistical treatments of the data should be independently veri-
fied and the quality control precautions noted.
3/ Concurrently in preparation, FY 85.
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B. Identify Data Gaps
Using the Data Submission Guideline on Magnitude of the
Residue: Crop Field Trials as a guide (in conjunction with the
related Guidelines on Analytical Method(s) and Storage Stability)/
the reviewer should then look for data gaps - omissions in the
information supplied by the petitioner/registrant in his report.
These should be duly noted in the reviewer's report, and a
judgment made as to which are considered significant enough to
adversely affect the review process. Those so identified should
be communicated back to the petitioner/registrant by the Product
Manager for corrective action.
C. Assess the Appropriateness and Adequacy of the Data
The data reviewer then considers the appropriateness (vis-a-vis
the intended use) and adequacy of the data/information that has
been supplied. The aforereferenced Data Submission Guidelines
are a useful guide to the various parameters that need to be
considered. Appendix 1 of this document discusses specific aspects
of those parameters that warrant consideration.
As an adjunct to these, the reviewer should draw upon the
technical guidance in the reviewer aids materials that are
available to him, such as the Residue Chemistry Guidelines (a.k.a.
Subdivision 0 of the Pesticide Assessment Guidelines). A listing
of some suggested source materials is located in Appendix 2 to
this document.
Any perceived deficiencies in the data/information supplied
should be identified and explained, with a statement as to what
steps should be taken to resolve the deficiencies, so that this
information can be relayed back to the petitioner/registrant by
the Product Manager for appropriate action.
Note; As stated in Footnote 1, other aspects of the Magni-
tude "of the Residue, such as processed food/feed and meat/milk/
poultry/eggs considerations are to be addressed in separate
Standard Evaluation Procedure documents (to be developed in FY 85).
Those considerations are applicable whenever a r.a.c. (or parts
thereof) may be utilized as an item of livestock or poultry
feed, or may be processed into feed items or human foods.
D. Determine the Need for Deferral/Referral(s) to Other
HEP Branches
In considering the appropriateness and adequacy of the
data/information that have been supplied, the data reviewer
must also determine if deferral/referral(s) to other HED
Branch(es) are germane to reaching that decision.
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If so, the specific nature of the deferral/referral(s)
should be clearly and succinctly stated and directed to the
specific Branch(es) whose input is sought. In the interim
period until the response(s) to such deferral/referral(s) are
received, final judgment on the issue(s) in question should be
withheld.
E. Conclude if the Requested Action is Supportable
As the last step in the data evaluation process, the data
reviewer makes a judgment as to whether the submitted data/infor-
mation support the requested action (tolerance/registration)
of the data submitter.
If the data are not supportive, possible alternative action(s)
that may be taken by the petitioner/registrant are suggested.
If deficiencies/omissions exist in the submitted data base,
the reviewer may have to defer judgment until such time as
appropriate corrective action has been rendered by the petitioner/
registrant.
(Note: As stated in D above, if deferral/referral(s) to
other HED Branch(es) have been made, final judgment will need
to be held in abeyance pending the response to such deferral/
referral(s).)
IV. REVIEWER AIDS
There are a large number and variety of source materials
that are available to assist the data reviewer in the evaluation
process. A listing of some of the more useful references that
reside within the Branch is provided in Appendix 2 to this
document.
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APPENDIX 1
MAJOR POINTS TO CONSIDER IN EVALUATING CROP FIELD TRIAL DATA
Include the following:
A. Field Treatments and Harvesting
1. The R.A.C.
- Has the r.a.c. been adequately identified in all
the field trials? .
- Are an. adequate number of types and varieties
represented?
Are the commercially important varieties represen-
ted?
Is it clear what specific plant part(s) were harves-
ted?
- Have the developmental stage(s) and general condi-
tion (e.g., immature/mature, green/ripe, fresh/dry,
etc.) of the r.a.c. at time of pesticide applica-
tion^) and at harvest been specified?
- Were the r.a.c. samples in any way trimmed, cleaned,
or otherwise subjected to a means of residue
removal at time of harvest? If so, were the recom-
mended procedures of P.A.M. I, §§141-2 followed?
Are there livestock or poultry feed items associated
with the r.a.c.? If so, are animal metabolism and
feeding studies available? (Note: these concerns
will be addressed in separate Standard Evaluation
Procedures to be developed in FY 85.)
Is the r.a.c. normally processed into feed or food
items? If so, have processing studies been conduc-
ted? (Ref. Footnote 1, page 1, this document.)
- Is supplementary information available for the pes-
ticide in other reports by the petitioner/registrant
on this r.a.c. or botanically related r.a.c.'s
that can be translated to support the data base,
if needed?
- Are data for the pesticide under similar use condi-
tions available on the representative r.a.c.'s of
the crop group to which this r.a.c. belongs and, if
so, should a crop group action be considered?
- Are the typical growing seasons (summer/winter;
wet/dry) of the r.a.c. represented, especially by
field trial data from CA and/or FL?
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Have geographically representative data been sub-
mitted for the major growing areas of the r.a.c.
(ref. USDA Agricultural Statistics)?
(Note: Determining factors as to what constitutes "adequate
geographic representation" include how widespread the crop is
grown, its economic importance and national acreage, the range
of conditions under which it is grown, whether a minor crop or
minor use is involved, what the intended use pattern is, what
data and tolerances exist on botanically related crops treated
with the same pesticide via a similar use pattern, and the
general concern over the toxicity of the pesticide.)
Is this r.a.c. considered a "minor crop" (i.e.,
limited acreage and low exposure)?
Have there been experimental use permits/temporary
tolerances, Section 18 exemptions, or Section 24(c)
registrations for the r.a.c. treated with this
pesticide? Permanent tolerance petition requests?
Are there Codex/FAO Monograph data available for
this r.a.c. or botanically related r.a.c.'s treated
with this pesticide?
- Are there international residue limits (IRL's)
established for use of this pesticide on this
r.a.c. and, if so, upon what use(s) were they
established and what components of the residue are
regulated? What would be required for harmonization
with any such IRL's?
- Is there any other unpublished or published infor-
mation known to us re this pesticide and r.a.c.
use that must be taken into consideration?
- Are all the important dates relative to the growing
and harvesting of the r.a.c. reported?
2. The Pesticide
Does each field trial specify what pesticide formu-
lated product(s) were applied?
- Has each pesticide formulated product been adequately
identified? (Detailed consideration of this should
be addressed in evaluating the formulation(s);
this will be the subject of a separate Standard
Evaluation Procedure to be developed in FY 85.)
- Has the EPA Registration Number been given?
Has the type of formulation (WP, EC, G, etc.) been
specified?
Has the active ingredient (a.i.) in the formulated
product been identified?
Is the purity of the a.i. known? Are there impurities
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of concern?
Is the percent a.i. in the formulated product stated?
Is the amount of a.i. per gallon, pound, etc. of
formulated product given? Are metric equivalents
given?
Is the photochemical stability of the pesticide
formulated product known?
Are the registered label(s) and proposed supplemen-
tal label(s) provided (or available somewhere in
the over-all data package; e.g., Section B of a
petition)?
- Were the field trials conducted with the proposed
commercial pesticide formulation(s) of intended
use?
- Were spray adjuvants used with the formulation
and, if so, are they identified as to nature and
amount? Does the proposed use indicate spray
adjuvants are intended to be used?
- Were there any tank-mates or other pesticides applied
to the r.a.c. and, if so, have they been adequately
identified?
- Was there any special carrier involved in the appli-
cation of the pesticide (e.g., encapsulating
polymer, cigarette filter tips, etc.)?
Is information available (e.g., Section A of a peti-
tion) on the stability and solubility of the
formulated product(s)?
Has this chemical been RPAR'd and, if so, what is
the current status?
- Is there a Registration Standard on this chemical
and, if so, is it being used in the evaluation of
these data?
3. The Experimental Design
Were field trials carried out in the major areas
of cultivation or production of the r.a.c. and
sited to cover the range of representative conditions
(climatic, seasonal, soil, cropping system, farming
practice, etc.) under which it is normally grown?
- Are the field trial lay-outs sufficiently described
and of adequate design (i.e., inclusion of control
plots, large enough plots, etc.)?
- Are there data for successive crop years?
Are trials properly identified and the collected
samples adequately labeled, dated, and coded?
Is the method of harvesting (mechanical/hand; from
the plant/ground/flotation; etc.) described?
- What steps were taken to assure random and represen-
tative sampling?
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Is the intended use considered a "minor use" in terms
of exposure?
- Were there a sufficient number of field trials con-
ducted on the r.a.c. to support the requested
action of the data submitter?
(Note: This is a judgment call and is influenced by the econo-
mic importance of the r.a.c./ national acreage of the r.a.c./
the range of conditions under which it is grown, how widespread
it is grown, how closely the trials corresponded with the
intended use pattern(s), whether exaggerated rate and residue
decline data are available, whether a minor crop or minor use
is involved, the data and established tolerances already avail-
able on botanically related crops treated with the pesticide
under similar conditions of use, the nature of the requested
action of the data submitter, and the general concern over the
toxicity of the pesticide.)
4. Application of the Pesticide
Do the field trials reflect the intended use (proposed
labeling) of the pesticide on the r.a.c.?
- Are data available reflecting the maximum proposed use
conditions (e.g., maximum dose rate(s), maximum number
of applications, minimum application intervals, minimum
preharvest interval (PHI), etc.)? If not, are the
available data sufficient to allow for extrapolation?
Do the method(s) of application (air/ground) and the
type of applications) [band/broadcast, soil/foliar/
directed, ultralow volume (ULV)/concentrate/dilute,
etc.) reflect the intended use?
- Are data available reflecting the minimum spray gallonage
per acre, especially for ULV intended uses?
- Are label restrictions needed?
Are exaggerated rate and residue decline data'(varying
PHIs) available?
- Was a description of the pesticide application equipment
provided?
Was the application equipment used similar to that in
local commercial practice?
- Are dose rates and spray volumes reported in a manner
(e.g., Ibs a.i./A or, for tree crops, for example,
X Ibs a.i. per Y gallons, use Z gallons per acre)
that is consistent with normal practice and with
the directions on the proposed labeling? Are metric
equivalents provided?
- Are the dates, number(s) and timing of the application(s)
given? Is this information tied in with the developmental
stage(s) of the r.a.c.?
Is information provided on tank-mates or other pesticide(s)
applied, if applicable (formulation(s), rate(s), date(s)
applied, etc.)?
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5. Quality Control
Are quality control measures to ensure the fidelity
of the crop field trials described?
Were proper records (e.g., field trial/sample history,
dates, weather, etc.) kept and duly reported?
Are responsible personnel adequately identified?
Was a petitioner/registrant contact person identi-
fied and a telephone number provided?
Was the application equipment calibrated?
B. Handling, Pre-Shipping Storage, and Shipping Procedures
for Harvested R.A.C. Samples
1. The R.A.C.
- Were the r.a.c. samples in any way trimmed, cleaned,
or otherwise subjected to a means of residue
removal during these operations? If so, were the
procedures recommended in P.A.M. I, §§ 141-2
followed?
How were the r.a.c. samples stored between harves-
ting and shipping (temperature, humidity, container
type(s)/size(s), etc.)?
How soon after harvesting did the r.a.c. samples
enter storage?
How long between harvesting and shipping?
- Were specific dates given for each of these opera-
tions for each of the field trials?
- Was any sample compositing or subsampling done at
these stages? If so, were details given?
2. General Procedure
- What were the method(s) of packaging samples for
shipment (container type(s)/size(s); sample
sizes; ambient/iced; labeling/dating/coding)?
What was the means of shipping the samples to the
laboratory?
- Were the dates of harvesting, entry into storage
before shipping, and shipping given?
3. Quality Control
What quality assurance measures were taken to ensure
the fidelity of harvested r.a.c. samples?
Were adequate records kept and has sufficient infor-
mation been submitted?
Were responsible personnel identified? Was a peti-
tioner/registrant contact person identified and a
telephone number provided?
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Conditiohs and Length of Storage of Harvested R.A.C.
Samples (following their receipt in the laboratory and
prior to residue analysis)
1. The R.A.C.
- Were the r.a.c. samples in any way trimmed, cleaned,
or otherwise subjected to a means of residue removal
upon their receipt in the laboratory and prior to
entering storage? If so, were the recommended pro-
cedures of P.A.M. I, §§ 141-2 followed?
- Were the r.a.c. samples stored whole, chopped, as
an extract, etc.?
- Was any sample compositing or subsampling done prior
to storage? If so, were details given? Were the
same sample code numbers maintained?
2. General Procedure
- What were the conditions of storage (temperature,
humidity, container type(s)/size(s), sample weights,
etc.)?
- What was the extraction procedure (if applicable)?
- What dates were samples received in the laboratory;
subsampled/composited (if applicable); chopped or
extracted (if applicable); and entered into storage?
3. Quality Control
- What quality assurance measures were taken to ensure
the fidelity of harvested r.a.c. samples?
Were adequate records kept and has sufficient infor-
mation been submitted?
- Were responsible personnel identified? Was a peti-
tioner/registrant contact person identified and a
telephone number provided?
D. Storage Stability Validation Testing
Refer to the Standard Evaluation Procedure on Storage Stability4
for guidance on this subject area.
E. Analyses to Determine the "Total Toxic Residue" in
Samples From Supervised R.A.C. Field Trials
1. The R.A.C.
- What specific plant part(s) were subjected to resi-
due analysis for a determination of the "total
toxic residue?"
4/ Concurrently in preparation, FY 85,
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Were all the appropriate plant part(s) subjected
to residue analysis? (Ref. Table II, Residue
Chemistry Guidelines.)
Are there food or feed items associated with the
r.a.c.? (If so, refer to the Standard Evaluation
Procedure dealing with that topic (to be developed in
FY 85).)
Were the r.a.c. samples in any way trimmed, cleaned,
or otherwise subjected to a means of residue
removal in preparation for the analysis of the
"total toxic residue?" If so, were the recommended
procedures of P.A.M. I, §§ 141-2 followed?
Was any sample compositing or subsampling done in
preparation for analysis of the "total toxic
residue?" If so, were details given? Were the same
sample code numbers maintained?
Was the sample/laboratory coding sufficiently
clear so that the history of the r.a.c. sample(s)
could be traced (e.g., treatment regimen, harvest
date, length of storage, extraction date, etc.)?
- Were control samples (field blanks, reagent blanks)
carried through the analytical procedure?
- Were there replicate r.a.c. samples per field treat-
ment regimen per plant matrix?
2. Residue Methodology and Instrumentation
Refer to the Standard Evaluation Procedure on Analyti-
cal Method(s)^ for guidance on this subject area.
3. Analytical Methodology Residue Results
Were blank values reasonably low? If not, is an
explanation provided?
- Are all the raw data reported rather than just
average values?
- Were any correction factors [e.g., method recovery,
extraction efficiency, field blanks, storage
stability] applied to the residue values reported?
- Is the method of calculating the residue values
adequately described [formulae, standard curves,
etc.], and illustrated, and the raw data sufficiently
detailed so that independent calculations to verify
the reported results can be made?
Were the residue values reasonably uniform for
replicate samples?
5/ Concurrently in preparation, FY 85.
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Does the petitioner/registrant claim any of the resi-
due values are outliners and, if so, can this claim
be supported?
- How do these residue results compare with those on
related botanical r.a.c.'s treated with this same
pesticide via the same, or similar, use pattern(s)
[provided such data are available]?
- How do these residue results compare with previously
submitted data [e.g., EUP/temporary tolerance,
Section 18 or 24(c) exemptions] for this r.a.c.
treated with this same pesticide via the same, or
similar, use pattern(s) [provided such data are
available]?
- Do these residue results support the action reques-
ted by the data submitter? If not, what action(s)
should the data submitter undertake to resolve the
perceived deficiencies?
- Are residue decline data [residues (ppm) vs. time
(PHI)] provided?
- Can harmonization with international residue limits
be achieved [if applicable]? If not, why not?
- Is there a Registration Standard for this pesticide
and, if so, is it being used by the reviewer in
the evaluation of these data?
4. Quality Control
- What quality assurance measures were taken to ensure
the fidelity of the analytical methodology residue
analyses?
- Was the sample/laboratory coding sufficiently clear
so that the history of the sample(s) used could be
traced?
Were the analyst's worksheets provided? Are they
sufficiently- detailed?
- Were the person(s) [supervisor, analyst] responsible
for the analytical methodology residue analyses
identified [name, title, organization, address, and
telephone number]?
Were the analytical methodology residue analyses
test report(s) authenticated (signed) by the
responsible personnel?
Is a contact person for the petitioner/registrant
given with title, address, and telephone number?
Were representative chromatograms, spectra, etc.,
as applicable, provided? Are adequate clean-up
and determination [i.e., low background "noise",
adequate signal-to-noise ratio, well-defined peaks
rather than shoulder bands, etc.] of the test
compound(s) indicated? The level of claimed sensi-
tivity valid?
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Was the methodology tested for possible interference(s)
from other registered pesticides?
- Are the calibration procedures for the instrumenta-
tion described?
Were tests performed for interference from storage
containers, reagents, plant substrates, plastic
labware, etc.?
- If statistical analyses were performed and applied
to the results of the analytical methodology
residue determinations, is sufficient information
provided to independently validate the results?
- Is a need for a laboratory audit indicated?
F. Analytical Methodology Validation/Recovery Testing
1. The R.A.C.
- What specific plant part(s) were subjected to analy-
tical methodology validation/recovery testing?
- Were the r.a.c. samples in any way trimmed, cleaned,
or otherwise subjected to a means of residue
removal in preparation for the analytical method-
ology validation/recovery testing? If so, were the
recommended procedures of P.A.M. !/.§§ 141-2
followed?
- Was any sample compositing or subsampling done in
preparation for analytical methodology validation/
recovery testing? If so, were details given?
Were the same sample code numbers maintained?
In what form [whole, chopped, extract, etc.] were
the r.a.c. samples [i.e., plant matrices] when
they were fortified?
2. The Test Compound(s)
- Were analytical reference grade standards of the
parent pesticide and any metabolite(s) of especial
concern [normally those which, in addition to
the parent, comprise the "total toxic residue," un-
less present in very minor amounts] used for
fortifications? Was the purity of these standards
given?
- Is it clear what test compound(s) were used for
fortification? For each of the plant matrices
tested?
Were the fortification ["spiking"] level(s) given
for each test compound? For each of the plant
matrices tested?
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Is it described how the test compound(s) were prepared
for the fortification process [i.e., what solute(s),
concentration of the standard solution(s), dilution
factors, etc.]?
- If "spiking" with a mixture of test compounds, was
testing done to ensure interference would be no
problem?
3. The Experimental Design
- Were all the necessary compounds [parent plus meta-
bolite(s) comprising the "total toxic residue"]
and plant matrices [specific r.a.c. parts] tested
for analytical methodology validation/recovery?
- Were the number and magnitude of the fortification
levels adequate and appropriate?
- Was there a fortification level to establish a vali-
dated sensitivity level?
- Was there a fortification level near the proposed
tolerance level?
- Were control samples [field blanks, reagent blanks]
carried through the procedure?
- Were the analytical methodology validation/recovery
tests conducted in conjunction with the analyses
of residues in r.a.c. samples from each of the
supervised crop field trials, or as a separate study?
Were there replicate samples per test compound per
fortification level per plant matrix?
- Are all the significant dates given [date of samples
receipt in laboratory; dates and length of storage,
if applicable; dates of test sample preparation
(chopping, extraction, etc.); date of test compound(s)
preparation (standard reference solutions); residue
analysis, including the determinative step]?
4. Residue Methodology and Instrumentation
- Was more than one analytical method used in the analy-
sis of r.a.c. field trial samples for the "total
toxic residue" [i.e., a "total" residue method and
perhaps separate method(s) for the metabolite(s)
of concern] and, if so, were each of those methods
subjected to validation/recovery testing?
Was the analytical methodology adequately identi-
fied [e.g., title/designation/date and source]?
- Is a complete copy [non-CBI] of each analytical
method that was used in the validation/recovery
study testing provided [or available in the over-all
data package] with a description of the principles
and the stepwise procedure [extraction/clean-up,
derivatization, determination], and is it clear
what chemical species could be determined?
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- .Is it clear if modifications were made in the analy-
tical procedure(s) and, if so, are they adequately
described?
- Is it clear at what step in the analytical proce-
dure^) the fortification occurred, and how this
was accomplished?
- Was the extraction efficiency of the analytical
methodology demonstrated [especially if dry r.a.c.
substrates were used or if the presence of "bound"
residues is suspected]?
- Were method sensitivity and the limit of detection
given? Were they suitably low?
- Was an internal standard used?
- Were any difficulties encountered in the procedure
[e.g., emulsions, etc.] and, if so, were they
adequately described and overcome?
- Were any esoteric reagents/equipment/instrumenta-
tion used?
Are the instrumentation [type, type/specificity of
detector(s), column(s) (size, packing materials),
carrier gas(es), etc.] and operating parameters
[flow rate(s), temperature(s), voltage, etc.]
specified? Adequately described?
How long did it take the analyst to run a sample
completely through the analytical procedure,
including the determinative step?
5. Analytical Methodology Validation/Recovery Results
- Do the results indicate the recoverability of the
test compound(s) in the plant matrices?
- Are recovery values acceptably high [ >_ 70%, except
in special cases; ref. Residue Chemistry Guidelines]?
- Were blank values reasonably low? If not, is an
explanation provided?
- Are all the raw data reported rather than just
average values?
- Were any correction factors [e.g., extraction
efficiency, field blanks, etc.] applied to the
residue values/recovery values reported?
- Are the methods of calculating the residue level
and.percent recovery adequately described [formulae,
standard curves, etc.], and illustrated, and the
raw data sufficiently detailed so that independent
calculations to verify the reported results can be
made?
6. Quality Control
What quality assurance measures were taken to ensure
the fidelity of the analytical methodology valida-
tion/recovery testing?
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Was the sample/laboratory coding sufficiently .clear
so that the history of the samplers) used could be
traced?
Were the analyst's worksheets provided? Are they
sufficiently detailed?
Were the person(s) [supervisor, analyst] responsible
for the analytical methodology validation/recovery
testing identified [name, title, organization,
address, telephone number]?
Were the analytical methodology validation/recovery
test report(s) authenticated (signed) by the
responsible personnel?
Is a contact person for the petitioner/registrant
given with title, address, and telephone number?
Were representative chromatograms, spectra, etc.,
as applicable, provided? Are adequate clean-up
and determination [i.e., low background "noise",
adequate signal-to-noise ratio, well-defined peaks
rather than shoulder bands, etc.] of the test com-
pound^) indicated?
Were the recovery values reasonably uniform for
replicate samples?
Are the calibration procedures for the instrumenta-
tion described?
Were tests performed for interference from storage
containers, reagents, plant substrates, plastic
labware, etc.?
If analytical methodology validation/recovery tests
were performed in conjunction with the analyses of
residues in r.a.c. samples from each of the super-
vised crop field trials, were the reference stan-
dards solutions freshly prepared each day? If
not, was their stability monitored?
If statistical analyses were performed and applied
to the results of the analytical methodology
validation/recovery testing, is sufficient informa-
tion provided to independently validate the results?
Is a need for a laboratory audit indicated?
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APPENDIX 2
REVIEWER AIDS MATERIALS1
Following is a listing of some of the more useful source
materials within the Residue Chemistry Branch that could prove
helpful in reviewing crop field trial studies:
(1) Federal Food, Drug, and Cosmetic Act, as amended,
§§ 408-409;
(2) Federal Insecticide, Fungicide, and Rodenticide Act,
as amended;
(3) Subdivision 0 [Residue Chemistry] of the Pesticide
Assessment Guidelines, §171-3 and §171-4, prepared
by OPTS/EPA, Washington, D.C. (1982);
(4) Subdivision D [Product Chemistry] of the Pesticide
Assessment Guidelines, prepared by OPTS/EPA, Washington,
D.C. (1982);
(5) Code of Federal Regulations [40 CFR 158 and 180;
21 CFR 193 and 561], General Services Administration,
Washington, D.C., updated annually;
(6) Pesticide Chemical News Guide, R. E. Duggan, editor,
Food Chemical News, Inc., Washington, D.C., 1982,
updated monthly;
(7) "Guidelines on Pesticide Residue Trials to Provide
Data for the Registering of Pesticides and the Estab-
lishment of Maximum Residue Limits," FAQ Plant Protec-
tion Bulletin, 29;l/2, pp. 12-27 (1981);
(8) "Guidelines for Data Acquisition and Data Quality Evalu-
ation in Environmental Chemistry", Anal. Chem. 52,
2242-2248 (1980);
(9) Acceptable Common Names and Chemical Names for the
Ingredient Statement on Pesticide Labels, 4th ed.,
C. R. Blalock, et al., editors, OPP/EPA, 1979,
available from National Technical Information Service,
Springfield, VA;
6/ A comprehensive listing is to be compiled in the future.
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(10) Farm Chemicals Handbook, Meister Publishing Co.,
Willoughby, OH, updated annually;
(11) Nanogen Index: A Dictionary of Pesticides and Chemi-
cal Pollutants, K. Packer, editor, Nanogens Interna-
tional, Freedom, CA, 1975 (updated periodically by
supplements);
(12) U.S.D.A. Agricultural Statistics, U.S. Government
Printing Office, Washington, D.C., updated annually;
(13) Crop Grouping Classification [40 CFR 180.34(f), as
revised 6/29/83 (48 PR 29855)];
(14) F.D.A. Pesticide Analytical Manual, Volumes I and II,
available from the National Technical Information
Service, Springfield VA;
(15) Plants Consumed by Man, B. Brouk, Academic Press, NY
(1975);
(16) Principles of Field Crop Production, 3d ed., J. H.
Martin, W. H. Leonard, and D. L. Stamp, Macmillan
Publishing Co., Inc., NY (1976);
(17) Crop Production, 4th ed., R. J. Delorit, L. J. Greub,
and H. L. Ahlgren, Prentice-Hall, Inc., NJ (1974);
(18) Food and Feed Crops of the United States, J. R. Magness,
G. M. Markle, and C. C. Compton, Rutgers University,
NJ (1971);
(19) McGraw-Hill Encyclopedia of Food, Agriculture & Nutri-
tion, D. N. Lapedes, editor-in-chief, McGraw-Hill
Book Company, NY (1977);
(20) "Guide for Estimating Toxic Residues in Animal Feeds
or Diets" prepared for the E.P.A. by Lorin E. Harris,
available from National Technical Information Service,
Springfield, VA;
(21) Feeds and Feeding, Abridged: The Essentials of the
Feeding, Care, and Management of Farm Animals, Including
Poultry, F. B. Morrison, 9th ed., The Morrison Publishing
Co., Ithaca, NY (1958);
(22) Statistical Methods Applied .to Experiments in Agricul-
ture and Biology, 7th. ed., G. W. Snedecor, Iowa
State College Press, Ames, IA (1980);
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(23) Foods and Food Production Encyclopedia/ D. M. Considine
and G. D. Considine, Van Nostrand Reinhold Company,
NY (1982);
(24) Registration Standards on various individual pesti-
cides, prepared by OPTS/EPA, (several issued each
fiscal year);
(25) Residue Chemistry Branch files: petition and regis-
tration files; cultural practices; reviewer aids;
policies; foreign uses; subject files; reading files;
card catalogue; et al.;
(26) Various reference texts and journal publications of
a scientific or agricultural nature, including
FAO/Codex Monographs.
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