Document ID: EPA-HQ-OPP-2012-0429-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-07-25T04:00Z

MacroButton macIb01 i  

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: [Kable Bo Davis (PM-25) 703-306-0415]

INSTRUCTIONS:  Please utilize this outline in preparing the pesticide
petition.  In cases where the outline element does not apply, please
insert “NA-Remove” and maintain the outline. Please do not change
the margins, font, or format in your pesticide petition. Simply replace
the instructions that appear in green, i.e., “[insert company
name],” with the information specific to your action.

TEMPLATE:

[BASF Corporation]

[Insert petition number]

	

	EPA has received a pesticide petition ([insert petition number]) from
[BASF Corporation], [26 Davis Drive, P.O. Box 13528, Research Triangle
Park, North Carolina 27709-3528] requesting, pursuant to section 408(d)
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d),
to amend 40 CFR part 180

(Options (pick one)

	1. by establishing a tolerance for residues of

	[Quinclorac, 3,7-dichloro-8-quinolinecarboxylic acid] in or on the raw
agricultural commodity [canola] at [1.0] parts per million (ppm).  No
tolerances are proposed for the processed commodities, meal and refined
oil, as no concentration of quinclorac residues is expected in these
commodities.  EPA has determined that the petition contains data or
information regarding the elements set forth in section 408 (d)(2) of 
FDDCA; however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of the
petition. Additional data may be needed before EPA rules on the
petition.

A. Residue Chemistry

	1. Plant metabolism.

[Plant and livestock metabolism studies previously submitted for
quinclorac are cited in support of this import tolerance petition for
quinclorac on canola.  A nature of the residue in canola included in
this submission is summarized here.

Radiolabeled quinclorac was applied to canola plants 30 days after
sowing at growth stage  ES 15 at a targeted application rate of 0.178 lb
a.i./A (200  g a.i./ha).  The actual application rate was 0.16 lb a.i./A
(181 g a.i./ha), about 1.8 times the maximum seasonal application rate.
Green plants were sampled pre-treatment and at 1 day and 29 days after
treatment (DAT).  Seed and straw were harvested at 60 DAT, consistent
with the proposed 60 day pre-harvest interval. The total radioactive
residue (TRR) in seed was 0.475 mg/kg. The samples were extracted with
acetone:pH 7 phosphate buffer (1:1 v/v) followed by 0.1 N NaOH at
ambient temperature and 0.1 N NaOH at 100°C.  TRR extracted from the
seed and straw was 96% and 88%, respectively.  The non-extractable
residues represented 2.7% and 12.2% of the TRR, respectively.  Based on
analysis of the seed extract by HPLC with radiometric detection, the
main radioactive residues in the seed were quinclorac ((37.1% TRR, 0.176
ppm) and the methyl ester, BH 514-ME (37.1% TRR, 0.176 ppm).  No other
residue >5% TRR was observed.

To remain consistent with the current residue definition for quinclorac
of parent only in the commodities of wheat, rice, sorghum and barley,
the proposed tolerances in canola seed are based on the residues of
parent quinclorac in canola seed. ]

	2. Analytical method. [An adequate analytical method for enforcement of
the tolerances exists. The analytical method used for quantitative
determinations was designed to measure quinclorac residues present as
the parent compound.]

	3. Magnitude of residues. [Magnitude of the Residue - Raw Agricultural
Commodities:  Canola field trials are predominately from Canadian sites
and were conducted using rates and timing intervals to represent the use
patterns, conditions and areas of use for this product in Canada. These
studies should be adequate to establish an import tolerance for canola
seed at the proposed 1.0 ppm level based on parent only.  Results from
19 field trials support the proposal that parent quinclorac can be used
to monitor the safe use of ACCORD Herbicide in canola. The tolerance
proposed was determined using the OECD calculator.

Based on the results of a processing study, residues of quinclorac do
not concentrate in meal or refined oil. 

The use in canola does not result in a maximum reasonable feed burden
for cattle, poultry or swine in excess of that already determined for
registered uses.  No additional data were needed in support of residues
in meat, milk, poultry and eggs.]

B. Toxicological Profile

	1. Acute toxicity.  [Based on available acute toxicity data quinclorac
does not pose any acute toxicity risks. Several acute toxicology studies
place technical-grade quinclorac in Toxicity Category III for acute
oral, acute dermal, acute inhalation toxicity, and for eye irritation.
Technical-grade quinclorac is in category IV for primary dermal
irritation and is a skin sensitizer. The soluble liquid end use
formulation of quinclorac (ACCORD SL) that is pending registration in
Canada (registered as Paramount, Facet L, and Drive XLR8 in US) has
tested negative for skin sensitization.]

	2. Genotoxicity. [Quinclorac was tested for its genotoxic potential in
a battery of six in vitro or in vivo studies covering the required
endpoints of point mutations, chromosomal damage and DNA damage and
repair.  Quinclorac did not demonstrate any genotoxic effects. 
Quinclorac was negative for inducing mutations in both an in vitro Ames
test and an in vitro forward mutation assay in mammalian cells (HGPRT
test with and without metabolic activation).  Both an in vitro and an in
vivo chromosome aberration assay (with and without metabolic activation)
showed no evidence of a clastogenic effect.  Unscheduled DNA synthesis
was not induced in the UDS assay.  A mutagenicity evaluation with
Bacillus subtilis (with and without metabolic activation) was also
negative. These studies demonstrate that Quinclorac is not genotoxic.]

	3. Reproductive and developmental toxicity. [Teratology - Rats: A
developmental study in rats fed dosages of 0, 24.4, 146, and 438
mg/kg/day (HDT) resulted in a developmental toxicity NOEL of 438
mg/kg/day and a maternal toxicity NOEL of 146 mg/kg/day based on reduced
food consumption, increased water intake, and mortality at 438 mg/kg/day
(HDT).  Under the conditions of this study, quinclorac did not produce
any sign of embryo/fetal toxicity and did not alter fetal morphological
development. 

Teratology - Rabbits:  A developmental study in rabbits fed dosages of
0, 70, 200, and 600 mg/kg/day resulted in a developmental toxicity NOEL
of 200 mg/kg/day based on an increase in resorptions and
postimplantation loss; a decrease in the number of live fetuses and
decreased fetal body weights at the 600 mg/kg/day dose level (HDT). At
all other treatment levels no embryo/fetal toxicity was observed. The
maternal toxicity NOEL is 70 mg/kg/day based on decreased body weight
gain and food consumption at 200 mg/kg/day; and increased water
consumption, increased mortality, and discoloration of the kidney at 600
mg/kg/day.  

Two-Generation Reproduction - Rats:  [A two-generation reproduction
study was conducted with rats dosed 0, 50, 200, and 600 mg/kg/day.  The
parental toxicity NOAEL is 200 mg/kg/day.  The parental LOAEL is 600
mg/kg/day, based on reduced body weight in both sexes during premating
and lactating periods.   The reproductive toxicity NOAEL is equal to or
greater than 600 mg/kg/day.  The developmental toxicity NOAEL is 200
mg/kg/day.  The developmental toxicity LOAEL is 600 mg/kg/day, based on
decreased pup weight and viability, as well as developmental delays.]

	4. Subchronic toxicity. [A 13-week feeding study in mice was conducted
at doses of 0, 4,000, 8,000, or 16,000 ppm; equivalent to 0, 1,000,
2,202 or 4,555 mg/kg/day for males and 0, 1,467, 2,735 or 5,953
mg/kg/day for females. The lowest observed adverse effect level (LOAEL)
is 1,000 mg/kg/day for males and 1,467 mg/kg/day for females based on
decreased body weight gains in males and females (17.6 and 18.7%,
respectively).

A 13-week feeding study in mice was conducted at doses of 0 and 500 ppm
(equivalent to 0 and 75 mg/kg/ day). The NOAEL is 75 mg/kg/day.

A 3-month feeding study in rats was conducted at doses of 0, 1000, 4000,
or 12000 ppm (0, 76.8, 302.3 or 929.9 mg/kg/day in males and 0, 86.7,
358, or 1,035.4 mg/kg/day in females). The NOAEL is 302 mg/kg/day
(male); 358 mg/kg/day (female). The LOAEL is 930 mg/kg/day (male); 1035
mg/kg/day (female) based on decreased body weight gain, food
consumption, and increased water intake in males and females, increased
SGOT, SGPT and focal chronic interstitial nephritis in males.]

	5. Chronic toxicity. [Chronic Feeding - Nonrodent:  A 1-year feeding
study in dogs fed 0, 34, 142, and 513 (males) and 0, 35, 140, and 469
(females) milligrams/kilogram/day (mg/kg/day) resulted in a
no-observed-effect level (NOEL) of 140 mg/kg/day based on reduced body
weight gains, adverse effect on food efficiency, hematological and
clinical chemistry values, increased liver and kidney weights, and
microscopic findings in liver and kidneys at 513 mg/kg/day (males) and
469 mg/kg/day (females), the highest dosages tested (HDT). 

Chronic Feeding/Oncogenicity - Rats:  A chronic feeding/carcinogenicity
study in rats fed dosages of 1, 56, 186, 385, and 487 mg/kg/day (males)
and 0, 60, 235, 478, and 757 mg/kg/day (females) resulted in a NOEL of
385 mg/kg/day (males) and 478 mg/kg/day (females) based on an equivocal
(uncertain) increase in acinar cell hyperplasia of the pancreas in males
at 487 mg/kg/day (HDT) and a slight decreases in weight for females at
757 mg/kg/day (HDT).  No carcinogenic effect was observed in rats. 

 Oncogenicity - Mice:  A carcinogenic study in mice fed dosages of 0,
37.5, 150, 600, and 1200 mg/kg/day resulted in no carcinogenic effects
observed under the conditions of the study up to and including 1200
mg/kg/day (HDT) and a systemic NOEL of 37.5 mg/kg/day based on a
reduction of body weight at 150 mg/kg/day.]

	6. Animal metabolism. [A metabolism study with rats receiving dosages
of 15, 100, 600 and 1200 mg/kg/day resulted in more than 90% of the
administered radioactivity eliminated in the urine within 5 days (most
within 24 hours) and 0.7%–3.7% in the feces. Radioactivity was mainly
associated with the unchanged parent compound. The glucuronic acid
conjugate of quinclorac was a minor (2%–5%) metabolite in urine.]

	7. Metabolite toxicology. [Reg. No. 161555 (the methyl ester metabolite
of Quinclorac found in plant) was studied in animal metabolism and
pharmacokinetic studies as well as toxicology studies.  

Male bile catherterized Wistar rats  received a single oral dose of 15
or 600 mg/kg bw. About 83% of dosed material was absorbed, rapidly
metabolized and excreted via urine, bile and feces. Less than 1% of the
dosed radioactivity remaining in the carcass after 72 hours.  The the
primary metabolite was found in urine and identified as quinclorac (at
46.71% and 15.34% of the dose for the low and high dose respectively). 
The unchanged Reg. No. 16155 was only found in in the feces (0.45% and
12.45% of the dose for the low and high dose respectively).  The
remaining characterized and identified residues were minor, none
amounting to more than 10% of the applied dose.

An acute oral toxicity study was conducted with rats given a single oral
gavage dose of Reg. No. 161555 at a dose level of 2000 mg/kg bw.   With
no resulting mortality, the oral LD50 was found to be greater than 2000
mg/kg bw.

A 90D feeding study was conducted in rats with Reg. No. 161555 at dose
levels of 0, 2000, 4000 and 8000 ppm (equal to 0, 128, 252, and 518
mg/kg bw/d for males and 0, 145, 274 and 509 mg/kg bw/d for females).  
Treatment resulted in a no-observed-adverse-effect level (NOAEL) of 2000
ppm for male (128 mg/kg bw/d) and 4000 ppm for female Wistar rats (274
mg/kg bw/d) based upon impaired body weight gain and effects observed in
the liver and thyroid target organs.]

	8. Endocrine disruption. [No specific scientific studies were conducted
to determine endocrine effects.  However, the toxicity testing described
above and conducted on three different animal species demonstrates no
apparent estrogenic effects or treatment-related effects of quinclorac
on the endocrine system.]

C. Aggregate Exposure

	1. Dietary exposure. [A dietary exposure assessment was conducted to
evaluate the potential risk from exposure to quinclorac in food and
drinking water.  The exposure assessment was conducted using all
currently established tolerances and the proposed new import tolerance
for canola. ]

Food. [Acute Dietary Exposure Assessment: The US EPA has determined that
an acute dietary assessment for quinclorac is only required for females
ages 13–49.  The exposure was calculated using tolerance level
residues, 100% crop treatment factors, and default processing factors. 
The consumption data was from the USDA Continuing Survey of Food Intake
by Individuals (CSFII 1994–1996, 1998) and the EPA Food Commodity
Ingredient Database (FCID) using Exponent's Dietary Exposure Evaluation
Module (DEEM-FCID) software.            

The acute NOAEL is 200 mg/kg bw/day and the FQPA safety factor is 1. 
The resulting acute Population Adjusted Dose (aPAD) is 2.0 mg/kg bw/day.
 The results from the acute assessment showed that the food and water
exposure represents less than 1% of the aPAD.

Chronic Dietary Exposure Assessment: The exposure was calculated using
tolerance level residues, 100% crop treatment factors, and default
processing factors.  The consumption data was from the USDA Continuing
Survey of Food Intake by Individuals (CSFII 1994–1996, 1998) and the
EPA Food Commodity Ingredient Database (FCID) using Exponent's Dietary
Exposure Evaluation Module (DEEM-FCID) software.            

The chronic NOAEL is 37.5 mg/kg bw/day and the FQPA safety factor is 1. 
The resulting chronic Population Adjusted Dose (cPAD) is 0.375 mg/kg
bw/day.  The results from the chronic assessment showed that children
ages 1–2 years old were the most highly exposed sub-population.   The
food and water exposure utilized 3.1% of the cPAD.  Table 1 below shows
the chronic exposure for all sub-populations. 

Table 1. Results for Quinclorac (BAS 514 H) Chronic Dietary Exposure
Analysis Considering all Tolerances using DEEM-FCID (food and water) 

Population	Exposure Estimate	%cPAD

Subgroups	(mg/kg b.w./day)	 

U.S. Population	0.0054	1.44

All Infants (< 1 year old)	0.0099	2.65

Children (1-2 years old)	0.0117	3.13

Children (3-5 years old)	0.0100	2.68

Children (6-12 years old)	0.0066	1.75

Youth (13-19 years old)	0.0044	1.16

Adults (20-49 years old)	0.0050	1.32

Adults (50+ years old)	0.0042	1.13

Females (13-49 years old)	0.0043	1.16

]

	ii. Drinking water. [The proposed import tolerances for canola will not
result in water exposure.  The use with the highest estimated drinking
water concentration is a section 18 use on cranberry.  The modeled acute
and chronic surface water concentrations are 77 ug/L and 70 ug/L,
respectively.  These drinking water values were included in the acute
and chronic dietary exposure assessment.  The acute water exposure for
females ages 13–49 utilized 0.19% aPAD.  The chronic water exposure
for the most highly exposed population sub-group, all infants, utilized
1.3% cPAD.]

	2. Non-dietary exposure. [Quinclorac is currently registered for use in
turf.  However, the US EPA has not selected a dermal endpoint for
quinclorac because no dermal toxicity was observed at the limit dose of
1000 mg/kg bw/day in the 21-day dermal toxicity study.  Therefore, a
dermal exposure assessment is not required.  For the turf use, an oral
exposure from hand-to-mouth and object-to-mouth for toddlers is
required.  The oral short- and intermediate-term NOAEL is 70 mg/kg
bw/day.  The toddler oral exposure and resulting MOE values from the use
of quinclorac on turf is shown in Table 2 below.  

Table 2.  Residential Exposure and Risk Estimates for Post-Application
Incidental Oral Exposure of Toddlers to Quinclorac on Turf.  

Acute Aggregate Exposure (Food and Drinking Water)

The aggregate acute risk includes residues of quinclorac from food and
water. Exposures from residential uses are not included in the acute
aggregate assessment.  The results demonstrate that there are no safety
concerns for any subpopulation based on established and new uses, and
that the results clearly meet the FQPA standard of reasonable certainty
of no harm.

Short- and Intermediate-Term Aggregate Exposure and Risk (food, water,
and residential)

Short-term aggregate risk from quinclorac takes into account exposures
from dietary consumption (food and water) and residential exposure from
turf use.  Short- and intermediate-term aggregate risk assessment is not
required for adults because there is no dermal exposure assessment
required.  The aggregate MOE from food, water, and residential oral
exposure for children 1–2 years old is 2700.  This MOE is greater than
the target MOE of 100 which indicates there is no safety concern.  

Chronic Aggregate Exposure and Risk (food and water)

The aggregate chronic risk includes residues of quinclorac from food and
water. Exposures from residential uses are not included in the chronic
aggregate assessment.  The results demonstrate there are no safety
concerns for any subpopulation based on established and new uses, and
that the results clearly meet the FQPA standard of reasonable certainty
of no harm.]

D. Cumulative Effects

	[BASF is not aware of any other EPA registered active ingredient that
is structurally similar to quinclorac or has a common mechanism of
toxicity.]

E. Safety Determination

	1. U.S. population. [Based on this risk assessment, BASF concludes that
there is a reasonable certainty that no harm will result to the general
population from the aggregate exposure to quinclorac.]

	2. Infants and children. [Based on this risk assessment, BASF concludes
that there is a reasonable certainty that no harm will result to infants
or children from the aggregate exposure to quinclorac.]

F. International Tolerances

	[There are no CODEX or Mexican maximum residue limits established for
quinclorac on canola.]

 PAGE   

 PAGE   5