&EPA
United States Prevention, Pesticides • April 2002
Environmental Protection and Toxic Substances
Agency (7508C)
Report of the FQPA
Tolerance Reassessment
Progress and Risk
Management Decision
(TRED)
Difenzoquat
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• UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
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^$S&2 9
**•- -*v OFFICE OF
PREVENTION. PESTICIDES AND
TOXIC SUBSTANCES
April 19, 2002
CERTIFIED MAIL
This is the Environmental Protection Agency's (hereafter referred to as EPA or the
Agency) "Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress
and Risk Management Decision (TRED) for difenzoquaf, which was approved on April 19.
'2002. A Notice of Availability of this tolerance reassessment decision will be published in the '
Federal Register (TR) shortly.
The Federal Food,.Drug and Cosmetic Act (FFDCA), as amended by FQPA, requires
EPA to reassess all the tolerances for registered chemicals in effect on or before the date of the
enactment of the FQPA. which was in August of 3 996. In reassessing these tolerances, the
Agency must-consider, among other things, aggregate risks from non-occupational sources of
pesticide exposure, whether there is increased susceptibility- to infants and children, and the
cumulative effects of pesticides with a common mechanism oftoxicity. Once a safety finding
has been made that aggregate risks are not of concern, the tolerances are considered reassessed.
A reregistration eligibility decision (RED) fordifenzoquat was completed in September 1994,
prior to FQPA enactment. Therefore, the tolerances need to be reassessed to meet the FQPA
standard. • . _ • • '
The Agency has evaluated the dietary- risk associated with difenzoquat and has
determined that there is a reasonable certainty that no harm to any population subgroup 'will-
result from aggregate exposure to difenzoquat when considering dietary exposure and all other
non-occupational sources of pesticide exposure for which there is reliable information.
Therefore, no mitigation'measures are needed, and the twenty two (22) tolerances established for
residues of difenzoquat in/on raw agricultural commodities are now considered reassessed as safe
under section 408(q) of the FFDCA. . .
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FQPA requires that EPA consider "available information" concerning the cumulative
effects of a particular pesticide's residues and "other substances that have a common mechanism
of toxicity." The reason for considering other substances is because of the possibility that low-
level exposures to multiple chemical substances that cause a common toxic effect by a common'
mechanism could lead to the same adverse health effect, as would a higher level of exposure to
any of the other substances individually. EPA did not perform a cumulative risk assessment as
part of this.review of difenzoquat, because the Agency'has not determined that there are any
other chemical substances that have a mechanism of toxicity common with that of difenzoquat.
If EPA identifies other substances that share a common mechanism of toxicity with difenzoquat,
then a cumulative risk assessment will be conducted that includes difenzoquat once the final
framework EPA will use for conducting cumulative risk assessments is available. Further, EPA
is in the process of developing criteria for characterizing and testing endocrine disrupting
chemicals and plans to implement an Endocrine Disrupter Screening Program. Difenzoquat will
be Devaluated at that time and additional studies may be required. .
• • The Agency's human health findings for the pesticide difenzoquat, were discussed in a
closure conference call, and are summarized in the enclosed chemical overview and summary of
the risk assessments. The risk assessments and other documents pertaining to the difenzoquat
tolerance reassessment decision are listed at the end of this document and are available on the
Internet at http://www.epa.gov/pesticides/reregistration/sl2tus.h1in and the public docket for
viewing. • • •_
Tolerances are established for'residues of difenzoquat. derived from application of the
methyl sulfate salt and calculated, in/on barley, wheat, and'animal commodities [Source: 40 •
CFR § 180.369]. Current tolerances range from 0.05 to 20 ppm for residues in/on barley and
wheat commodities, and are 0.05 ppm for residues in livestock commodities. Adequate
enforcement methods are available for the determination of difenzoquat residues in/on plant and
animal commodities.
The Agency has recommended establishing tolerances in processed commodities, barley-
bran; wheat bran and wheat shorts at 0.25 ppm and has reassessed,the tolerances for wheat straw,
barley straw, and barley grain at 5.0, 5.0 and 0.05 ppm, respectively. Fat, meat, and meat
byproducts of poultry are being reassessed each at 0.05 ppm. (See Table I)
The available livestock feeding data suggest that the established tolerances for residues of
difenzoquat in ruminant meat are adequate. However, actual reassessment of ruminant meat
tolerances will be made when the requested residue data for all major livestock feed (wheat
forage and hay; and barley hay) items have been submitted and a re-calculation of maximum .
dietary burden has been performed. Meanwhile, the label restriction against the grazing of
livestock on treated fields and the cutting of treated forage for silage/hay should remain on the
label, until forage and hay data are submitted and. evaluated.
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The Codex Commission has not established or proposed maximum residue limits (MRLs)
for residues of difenzoquat in/on various raw agricultural' and processed commodities.
Therefore, there are no inquiries with respect to compatibility of U.S. tolerances with Codex
MRLs. • ' . • • ' •
Table I. Tolerance Reassessment Summary for Difenzoquat
Commodity
Current Tolerance
(ppm)
Tolerance Reassessment
(ppm)
Comment
Tolerances listed imder 40 CFR -§180.369
Barley, grain
Barley, straw
Cattle, fat '
Cattle (mb'yp)
Cattle, meat '
Goats, fat
Goats (mbvp)
Goats, meat
Hogs, fat
Hogs (mbyp)
Hogs, meat
. Horses, fat
• Horses (mbyp)
Horses, meat
Poultry; fat
Poultry (mbyp)
Poultry, meat
Sheep, fat
Sheep (mbyp)
Sheep, meat
Wheat, grain
Wheat, straw
0.2
20 .
0,05
• ' 0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
20
0.05 .
' ' " 5.0
TBD
TBD
TBD.
TBD
TBD
TBD
'TBD
TBD .
TBD
TBD
TBD
TBD
0.05
0.05 -•
. 0.05
TBD
TBD
TBD
. 0.05
5.0"
[Cattle, meat
byproducts]
[Goat, fat]
[Goat, meat bvproducts]
[Goat, meat]
[Hog, fat]
[Goat, meat byproducts] -
fHog. meat]
[Horse, fat]
[Horse, meat
byproducts]
[Poultry; meat
byproducts]
[Sheep, meat byproducts]
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Tolerances That Need To be Proposed Under 40 CFR §180.369
Wheat, bran
Barley, bran
Wheat, shorts
None
None
None
0.25
0.25
0.25
Note that technical registrants will be sent a Section 3(c)(2)(B) Data-Call-in (DCI) letter
under the Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) in a separate mailing. If you
have questions on this document, please contact the Chemical Review Manager, Tawanda
Spears, at (703) 308-8050.
Sincerely,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Enclosures: "Difenzoquat Overview" and "Difenzpquat Summary"
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OVERVIEW OF DIFENZOQUAT
RISK ASSESSMENT
April 18,2002
This document summarizes EPA's human health risk and drinking water exposure
assessments for the methyl sulfate pesticide difenzoquat, (broadly classified as apyrazole) as
presented fully in the documents, "Difenzoquat: HED Human Health Risk Assessment for the'
Tolerance. Registration Eligibility Decision (TRED),'? dated February 11,2002, and "EFED
•.Drinking Water Exposure Assessment for the Tolerance Rere'gistration Eligibility Decision on
Difenzoquat," dated October 29,2001. The purpose of this overview is to assist the reader by
identifying the key features and findings of these risk assessments, and to better understand the
conclusions reached in the tolerance reassessment. References to relevant sections in {he
complete documents are provided to allow the reader to find the place in these assessments where
a more detailed explanation is provided. This overview was developed in response to comments
and requests from the public which indicated that the risk assessments were difficult to
understand, that they were too lengthy, and that it was not easy to compare the assessments for
different chemicals due to the use of different formats.
The difenzoquat risk assessment and additional supporting documents, are posted on
EPA's Internet website (http://www.epa.gQV/pesticides/difenzdquathtml) 'arid'are available in the
Pesticide Docket for public viewing. The Agency's report on the FQPA tolerance reassessment
decision for difenzoquat will be announced and made available to the public through a Federal
Register Notice. Prior to publication of the Notice, the Agency plans to conduct a closure
conference call to describe the risk and tolerance reassessment findings that will be presented in
theTRED.
The Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality •
Protection Act (FQPA) of 1996, requires EPA to review all the tolerances for registered
chemicals in effect on or before the date of the enactment of FQPA. In reviewing these
tolerances, the Agency must consider, among other things, aggregate risks from non-
occupational sources of pesticide exposure, whether there is increased susceptibility to infants
and children, and the cumulative effects of pesticides with a common mechanism of toxicity.
The tolerances are considered reassessed once the safety finding has been made or a revocation
occurs. A reregistration eligibility decision (RED) for difenzoquat was completed in September,
1994 prior to FQPA enactment; therefore, tolerances needed to be reassessed to reflect the
provisions of FQPA.
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Risks summarized in this document are those that result only from the use of difenzoquat
The FQPA requires that the Agency consider "available information" concerning the cumulative
effects of a particular pesticide's residues and "other substances that have a common mechanism
•of toxicity." The reason for consideration of other substances is due to the possibility that low-
level exposures to multiple chemical substances that cause a common toxic effect by a common
mechanism could lead to the same adverse health effect as would a higher level of exposure to
any of the other substances individually. The Agency did not perform a cumulative risk
assessment as part of this tolerance reassessment of difenzoquat because the Agency has not yet
identified any other chemical substances that have a mechanism of toxicity common with that of
difenzoquat. If the Agency identifies other substances that share a common mechanism of
toxicity with difenzoquat, then a cumulative risk assessment will be conducted that includes
difenzoquat. . .
Herbicide: Registered for use on the following crops/sites: selective control of wild oats
in wheat and barley. In addition, there are Special Local Needs [24(c)j registrations for
the states of Washington, Oregon, and Idaho to control wild oats in Kentucky bluegrass
grown only for seed production. . '
Formulations: Formulated as a 2 Ib cation/gal soluble concentrate (SC/L; EPA Reg. No.
241-266) and a 92.5% water dispersible granule (WDG; EPA Reg. No. 241-354).
Methods of Application: Difenzoquat may be applied by broadcast ground of aerial
applications in water spray volumes of 5-20 gal/A and 3-10 gal/A, respectively.
Timing: These products are registered for a single post-emergence application per
growing season to barley and wheat at a maximum rate of 1 Ib cation/A.. Application may
be made to: (i) barley when plants are in the 2- to 7-leaf stage; (ii) fall-seeded wheat
when plants are in the 4-leaf to tiller stage; and (iii) spring-seeded wheat when plants are
in the 5-to 6-leaf stage.
Annual Poundage: Based on data from 1995 through 2000, an annual estimate of
difenzoquat total domestic usage averaged 235,000 pounds of active ingredient for over
one million acres treated. The largest market in terms of total pounds of active ingredient
is allocated to wheat (65%) and barley (35%); use on bluegrass grown for seed is very
low. Most of the usage is in Minnesota, Montana, North Dakota, and Washington.
Weighted average percentile of crop treated is 2% for both barley and wheat.
Registrants: BASF Corporation
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Acute Dietary (Food) Risk
Acute dietary risk is calculated considering what is eaten in one day Acute dietary
exposure that is less ftan 1W% of the acute Population Adjusted Dose (aPADjtes tol^ceed
S ler? °f concem: Tte aPAD is the reference dose (RfD) adjusted fo the FQPA
^^^
fC^,dietaiy risk assessment was not conducted for difenzoquat because the Agencv
d et f " M "^ hT d (n° adV6rSe ^ W6re ~ed *** exp?surtra 7
single dose) Therefore, .an acute reference dose (aRfD) was not established. The only acute
.effects incrte in the database (suggestive of irritation) were considered to be atob^ed to fcl
method of administration of the test article (gavage) or did not result from
Chronic Dietary (Food) Risk
™ - risk is calculated by using the average cons'umptdon values forfood and
average residue values on those foods over a lifetime or the
se
SSo^SSl ^Cta°rff ^^-W^^BTye^fafance
AdimtedZ^P An^C ^ eXP°SUre ^ is le$S than 100% of &e cto0^ Population
Adjusted Dose (cPAD) does not exceed the Agency's level of concern. The cPAD is S cSonic
reference dose (cRfD) adjusted for the FQPA Safety Factor. The chronic RfD iTme dose t^
SIT ^ ^ eXP°Sed °Ver ^ C°WSe °f a Kfetime ^ -^verst heaS
, ,- .^.c^c dietary analysis for difenzoquat was conducted using a conservative '
detenmnistic (Tier I) analysis which assumes tolerance level residues bald on eSZ
reassessed to erances and 100 % crop treated. The chronic dietary exposure SSis
conducted using the Dietary Exposure Evaluation Model (DEEM™). A three-d^ averL of
consumption for each subpopulation is combined with tolerance residues in cotlodiS to
determine average exposures in mg/kg/day. ^mmoames to
and aU population subgroups (<1% of the cPAD). .
The toxicity endpoint for the chronic dietary is consistent decreases in body wei^t and
body welght gam in fee absence of decreased food consumption based on e Sine
^ (N°AEL=25 ^*^ ^ «*
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-reared; ^ (iv) Jdi^^^^tSSr±S» ** "
imderestmate the potential exposures for infante and children. mSW11Inot
• There is no evidence of endocrine disruption upon exposure to difenzoquat,
Drinking Water Dietary Risk
^^
gcT^-^^^
end estimates of exposure S atol of t? M^ ^-^^ a/sessment *>d Prides high-
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Estimated drmkong water concentrations for ground water are based on the Screening
Concentration in Ground Water (SCI-GROW) model, which is a conservative T^T
assessment that provides a high-end estimate. conservative, Tier I
Estimated drinking water concentrations for surface water are based on the Index
For chronic risk, potential exposure to difenzoquat from drinking water derived from
'
Residential Risk
exposure is not necessary.
Aggregate Risk
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Occupational Risk
No new data have been received to warrant ajreevaluation of the decision in the 1994
difenzoquat RED. , .
No new data have been received to warrant a reevaluation of the decision in the 1994
difenzoquat RED. • .
Several data deficiencies have been identified for difenzoquat. Studies required by the
Agency include: (i) UV/visible absorption (830.7050); and (ii) wheatand barley hay and wheat
forage field trial residue studies (860.1500). The deletion of the current forage/hay
grazing/cutting restriction will be deferred until tolerances for hay and forage are established
following the submission and review of the field trial data listed above.
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Difenzoquat Summary
Uses ...'•'••.. . • ' '
; is herbicide used for selective conWl of wild oats in v,heat and
Difenzoquat is;
barley.
only for seed production
estimates:
Effects
.' Noacu.ehazardendpctattncadverseeffects.ereassociated^^csuretoa
single dose) was identified.
. Chroniceffectswereconsistentdecreasesinbod^eighta.dtody.eigh.gainin
the absence of decreased food consumption.
There is no evidence of endocrine Eruption upon exposure , o difenzo,m,.
Risks
-•• V .'... Acute and Chronic Dietary (food and Water) Risks from exposure to difenzoqua,
are not of concern.
. Residential Risk is not of concern because there are no resident uses currency
registered for'difenzoquat. • • • . •
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t
±?are expected to be far less than the Agency's level of concern for aggregate
exposure of any U.S. population subgroup.
Worker /Ecological Risks- previously assessed in the difenzoquat RED issued in
September 1994.
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