vvEPA
United States
Environmental Protection
Agency
Prevention, Pesticides,
And Toxic Substances
(H7508W)
EPA738-B-93-001
February 1993
Pesticide Reregistratipn
Rejection Rate Analysis
Residue Chemistry/
Environmental Fate
Follow Up Guidance For
Conducting Rotational
Crop Studies
Recycled/Recyclable
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at least 50% recycled fiber
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
FEB 2 3 1993
OFFICE OF
PREVENTION, PESTICIDES AND
TOXIC SUBSTANCES
MEMORANDUM
SUBJECT:
FROM:
Guidance on How to Conduct Studies on Rotational Crops.
Ed Zager, Chief
Chemistry Branch II: Reregistration
Health Effects Division (H7509C)
and
Debra Edwards, Ph.D., Chief
Chemistry Branch I: Tolerance Support
Health Effects Division (H7509C)
TO:
Peter Caulkins, Acting Director
Special Review and Reregistration Division (H7508W)
and
Lawrence Culleen, Acting Director
Registration Division (H7505C)
THRU: Penelope A. F
Health Effect
jae^Crisp, Ph.D.
Division (H7509C)
Director
Earlier this year the Chemistry Branches of HED took over
responsibility for the review of data generated on rotational crops
(Guideline No. 's 165-1 and 165-2) . The attached paper was prepared
by a team consisting of Dr. R. Perfetti, Dr. R. Lor anger, Dr. W.
Hazel, F. Suhre, M. Rodriguez and R. Quick in order to provide
guidance to Registrants and Chemistry Branch personnel on how to
conduct and review these studies. This document will be utilized by
the Chemistry Branches in future reviews of rotational crop
studies .
We recommend that this paper be provided to all interested parties.
cc (With Attachment): L. Rossi, S. Irene, RBP, RF, Petition
Review Aids File and Rotational Crops File
Recycled/Recyclable
Printed with Soy/Canola Ink on paper that
contains «t least 50% recycled fiber
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GUIDANCE ON HOW TO CONDUCT STUDIES ON ROTATIONAL CROPS
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INTRODUCTION
The Chemistry Branches of Health Effects Division (HED) have taken
over the responsibility for review of studies which determine
whether pesticide residues of concern result in rotational crops as
a result of uptake from soil of previously treated fields
(Guideline Nos. 165-1 and 165-2). This transfer was performed
because the concern over residues in these situations is chiefly
dietary. The following paper is intended to provide additional
guidance to HED personnel and other interested parties as to the
requirements and procedure for review of submitted studies.
HISTORICAL
Studies on "Confined Rotational Crops" (Guideline Number 165-1) and
"Field Rotational Crops" (165-2) are conditionally required under
40 CFR 158 for uses of pesticides on terrestrial food crops and
aquatic food crops. As stated in Subdivision N, a rotational crop
use is any field-vegetable crop use, aquatic crop use or any other
site use on which it is reasonably foreseeable that any food or
feed crop may be produced after application of a pesticide. The
purpose of these studies is to determine the nature and amount of
pesticide residue uptake into rotational crops. The confined study
uses radioactive material applied to a small plot (often
laboratory/greenhouse). Results of these "hot" studies are used to
determine whether field studies (using non-radioactive pesticide)
are needed to measure residues in rotational crops grown under
actual field conditions. Based on these data appropriate crop
rotation restrictions (time from application to planting of
rotational crop) may be established and the need for tolerances on
the rotated crops determined.
Review of these studies has been conducted by the Environmental
Fate and Ground Water Branch (EFGWB) in the Environmental Fate and
Effects Division (or its predecessors in earlier organizations of
OPP) . Presumably this assignment was based on the importance of
soil residues as a factor in determining levels of residues in
rotational crops.
Traditionally the confined study has served as a worst-case
indicator of whether residues could occur in rotational crops. The
study is often conducted indoors using potted plants, conditions
which would tend to reduce the dissipation of the pesticide in the
soil. Until recently, if detectable residues of concern were found
in the crop during the confined study after the proposed rotational
crop interval, the field trials would normally be required to
assess whether residues occur in rotational crops under actual
growing conditions. In some cases registrants have volunteered to
perform field studies to refute results of the confined study,
especially if the registrant did not want a rotational crop
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interval on the label. If detectable residues were found in the
field studies for crops having a 12 month plantback interval (or
after a shorter interval the registrant desired on the label), the
registrant would be directed to seek a tolerance under the FFD&CA.
In this case, a tolerance petition was submitted and responsibility
for review shifted to the Chemistry Branch in HED.
Recently, EFGWB has been using the results of the confined studies
alone to determine whether tolerances are required for rotational
crops. Under this revised process, EFGWB has deferred to
Toxicology Branch when radioactive residues of the parent compound
or closely related metabolites were found in the crops during the
hot study. In other words, the field trials have been eliminated
as an early step in determining the need for rotational crop
tolerances. Under that procedure, if Toxicology Branch (TOX)
concluded that the residues identified in the confined study were
not toxicologically significant or, if they were toxicologically
significant, but the levels present were not toxicologically
significant, then no tolerance was required. However, if TOX
concluded the opposite, the registrant was referred to the
Chemistry Branches in HED.
Scientific Considerations
Confined Rotational Crop Studies; 165-1
The protocol for performing the three required confined rotational
crop studies (small grain, leafy vegetable and root crop) is
provided in Pesticide Assessment Guidelines Subdivision N.
Acceptance Criteria were discussed in the Agency's Phase 3
Technical Guidance Document. Confined rotational crop studies are
essentially metabolism studies; therefore, it is recommended that
the publication entitled "Additional Guidance for Conducting Plant
and Livestock Metabolism Studies" (7/16/92) be consulted before
conducting a confined rotational crop study. (It should be noted
that, in the case of confined rotational crop studies, the
application rate is IX, not an exaggerated rate.) . This paper will
refer frequently to that document when discussing various phases of
the subject experiments. A flow diagram describing the approach
discussed in this paper is provided in Figure 1 at the end of this
document.
The following should be considered when a confined rotational crop
study is to be conducted. The test material should be the pure
active ingredient radiolabeled (PAIRA) with C in a non-labile
position (e.g., in a ring). The parent compound only should be
applied to the appropriate soil type (usually a sandy loam) at the
maximum label rate (IX) and the required three rotated crops
(small grain, leafy vegetable and root crop) should be planted at
appropriate soil aging intervals (e.g, 1, 4, 7 or 9, and 12
months) . Sampling of the soil is not required and need only be
performed at the Registrant's discretion. The crops should be
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harvested and the appropriate plant parts (see Pesticide Assessment
Guidelines Subdivision O, Table II) should be sampled and combusted
to determine the total radioactive residue (TRR). At this point, if
each of the three crops demonstrate a TRR of <0.01 ppm in edible
portions at one of the plantback or soil aging intervals then the
Chemistry Branches will conclude that no further work and no
tolerances are needed. An appropriate rotational crop restriction
can be set at the shortest interval where no TRR is >0.01 ppm,
provided that the Registrant is willing to place this interval on
the label. If the TRR is <0.01 ppm in all three crops at the one
month interval, then no plantback restriction will be needed on the
label. If, however, in the three confined studies, the minimum
intervals at which the TRR is <0.01 ppm differ, then the rotational
crop restrictions will be set at the interval appropriate to each
tested crop group with the longest interval being applied to all
other (untested) rotated crops. The following example should be
considered:
The TRR for leafy vegetables is <0.01 ppm at the 1 month
plantback interval, the root crop TRR is <0.01 ppm at the 4
month interval and the grain crop TRR is <0.01 ppm at the 9
month interval. The rotational crop restrictions would be 1
month for leafy vegetables, 4 months for root crops and 9
months for small grains and all other rotated crops.
It is the Registrant's prerogative to perform additional confined
rotational crop studies on other crops to establish less
restrictive intervals based on levels of radioactivity.
In rare cases, TOX may have concerns regarding the presence of a
pesticide or metabolite at levels <0.01 ppm. Determination of the
presence (or absence) of specific metabolites of concern at levels
<0.01 ppm may be required in these cases.
If any of the plants in the confined studies exceed the trigger
value (0.01 ppm) at the 12 month interval, then the nature of the
residue in those test crops having a TRR >0.01 ppm must be
determined. The Registrant is referred to the 7/16/92 guidance
document discussed above (see also the comment regarding the
application rate for confined rotational crop studies) for a
description of the procedures which need to be followed to
accomplish this determination. If any one of the three crops shows
<0.01 ppm at a given interval but the Registrant desires a shorter
interval on the label for that crop where the TRR is >0.01 ppm,
then the composition of the TRR in that rotated crop (at the
desired interval) should be determined as described above for the
crop parts where the trigger value (i.e., 0.01 ppm) was exceeded.
If several samples of the crop are available at the desired
interval, the sample having the highest TRR should be utilized. In
either of the above cases, this information is needed in order that
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the Agency can make a conclusion as to whether the residue is an
inadvertent residue of no concern or whether cold field trials are
needed to make that determination.
If the metabolism in rotated crops appears to be different than
that in the primary crop, that is, if different metabolites are
observed in rotated crops than in primary crops, the Agency will
make a determination as to whether the different rotational crop
metabolites are of concern at the levels observed. If necessary,
the HED Metabolism Committee will be consulted to expedite this
decision.
The following are examples of the situations described above;
The primary (target) crop metabolism studies indicate that the
parent and metabolites A, B, C, D and E are present in the plant.
The Agency decides that only the parent and metabolite B need to be
regulated in the tolerance expression. The following three
scenarios might be encountered regarding rotational crops:
1) The confined rotational crop studies indicate that the TRR is
>0.01 ppm and that parent and metabolites A, B, C and D are
present. Limited rotational crop field trials will normally be
required with analysis for parent and metabolite B if it is
determined that these residues could be present at detectable
levels. If, however, metabolites A, C and D are present at much
higher levels in the rotational crops than in the primary crop, the
HED Metabolism Committee may be consulted as to whether the other
metabolites need to be quantitated.
2) The confined rotational crop studies show that the TRR is >0.01
ppm and that the radioactive residue consists of no parent and
metabolites D and E. In this case the Agency would normally
conclude that this is an inadvertent residue of no concern
situation and no field trials would be required. A rotational crop
restriction may be necessary. As above however, if metabolites D
and E are present at much higher levels in the rotational crops
than in the primary crop, the HED Metabolism Committee may be
consulted as to whether these metabolites need to be quantitated.
3) The confined rotational crop studies indicate that the TRR is
>0.01 ppm and that there is no parent present but that the major
portion of the TRR consists of a new metabolite F. This will
require a decision, as to whether there is toxicological concern
over the new metabolite. At this point the HED Metabolism Committee
may be consulted for an expedited decision. If it is concluded that
the metabolite is of concern at the levels likely to be present,
then F should be analyzed for in the limited rotational crop field
trials. If it is decided that F is of no concern then, as in 2
above, this is an inadvertent residue of no concern situation and
no field trials are necessary. However, a rotational crop
restriction may be necessary.
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It is recommended that the confined studies be submitted to the
Agency as soon after completion as possible, so that the Agency can
make a conclusion as to whether there is a potential inadvertent
residue of concern (i.e., will limited field trials be needed ?) as
expediently as possible. This will allow the Registrant to design
the field trials in a more efficient manner (i.e., what compounds
require analysis in the field trials).
Field Rotational Crop Studies (Limited and/or Extensive!; 165-2
If the level of the total radioactive residue in the confined
rotational crops exceeds 0.01 ppm at the desired rotational
interval or at 12 months, and once the nature of the residue in the
rotational crops is understood, then the Registrant should consider
the Agency's position regarding the residue to be regulated in the
primary crop (see discussion above) to decide whether the first
tier of field trials should be initiated. That is, if the
composition of the TRR in the rotational crops is such that
residues which are regulated in the primary crop are observed at
levels £0.01 ppm in the rotational crop (following the criteria set
forth in the 7/16/92 document with the exception of exaggerated
application rates), then field trials should be performed. For
further guidance on the protocols for carrying out these trials see
Pesticide Assessment Guidelines Subdivisions N and O as well as the
following comments.
The limited field trials should be conducted on a representative
crop (as defined in 40 CFR 180.34 (f)) at two sites per crop for
the following 3 crop groups: root and tuber vegetables , leafy
vegetables and cereal grains for a total of 6 trials. The 6 trials
should be conducted on a specific crop in each of the three crop
groups which the Registrant intends to have as a rotational crop on
the label. The soil should be treated at the maximum label rate and
the maximum number of applications and the appropriate crops should
be planted after the minimum aging interval. The crops should be
'harvested and all of the plant parts prescribed in Subdivision O,
Table II should be analyzed for the residues of concern observed in
primary crops as well as any other residues of concern specific to
rotational crops which fulfill the criteria set forth in the
Confined Rotational Crop section of this paper. Detection limits
for rotational crops should be comparable to those for primary
crops.
If no detectable residue are observed in raw agricultural
commodities in the limited field trials, then no tolerances will be
needed. However plantback restrictions will normally be needed
unless confined or field studies show no detectable residues of
concern at a 30 day plantback interval.
If the limited field studies above indicate that detectable
residues will occur, then rotational crop tolerances will be
required. The requirement for number of trials would be the same as
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that to establish primary tolerances on all crops (or crop groups)
which the Registrant intends to have as rotational crops on the
label. If the Registrant desires to allow the "universe" of crops
to be rotated, then magnitude of the residue data is required on
representative crops (see 40 CFR 180.34 (f)) for all crop groups
which could be planted in a typical crop rotation sequence. With
respect to treatment, these trials should be conducted in the same
manner as discussed above for the limited trials. If the Registrant
believes that a lesser number of crops would be rotated because of
the nature of the pesticide or due to the way it is used, then
guidance should be obtained from the Agency regarding specific data
requirements in that case. If tolerances exist on the crops to be
rotated as a result of a primary use, then rotational data on these
crops would be required only if residues in rotated crops are
significant in comparison to those in the primary crop.
Regulatory Considerations
It is the Agency's position that data waivers or agreements
concerning rotational crop requirements granted previously by
EFGWB/EFED should continue to be effective under this new guidance
and therefore HED will not reactivate rotational crop data
requirements in these cases.
In the future, under revised Guidelines, the limited field
rotational crop requirement may be altered so that an increased
number of limited field trials will be required. This requirement
will not be applied retroactively.
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