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**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 ] [ In sert petition number ] EPA has received a pesticide petition ( [ insert petition number ] ) from [ BASF Corporation ] , [ 26 Davis D rive, P.O. Box 13528, Research Triangle Park, North Carolina 27709
- 3528 ] request ing, 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 tol erance for residues of [ Quinclorac, 3,7

- dichloro

- 8
- quinolinecarbox yl ic 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 fo r 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 day s 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 actual2

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 day s 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 b uffer (1:1 v/v) followed b y 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 , respectivel y. Based on anal ys is of the seed extract b y HP LC with radiometric detection, the main radioactive residues in the seed were quinclorac ( (37.1% TRR, 0.176 pp m) and the methyl ester, BH 514

- ME (37.1% TRR, 0.176 ppm). No other residue >5% TRR was observed. To remain consiste nt with the current residu e definition for quinclorac of parent onl y 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 anal yt ical method for enforcement of the tolerances exists. The analy tical 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 quin clorac does not pose any acute toxicity

risks. Several acute toxicology studies place technical

- grade quinclorac in Toxicity

Category I II for acute oral, acute dermal, acute inhalation toxicity , and for ey e irritation. Technical

- grade quinclorac is in cate gory IVfor 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 se nsitization.] 2. Genotoxic i ty. [ Quinclorac was tested for its genotoxic potential in a battery of3

six in vitro or in vivo studies covering the required endpoints of point mutations, chromosomal damage and DNA damage and repair. Quinclorac did not demons trate an y 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 chromo some aberration assay

(with and without metabolic activation) showed no evidence of a clastogenic effect. Unscheduled DNA s ynthesis 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 developmenta l toxicity

NOELof 438 mg/kg/day and a maternal toxicity

NOELof 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 r esorptions 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 NOE L 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 t oxicity 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 delay s. ] 4. Subchronic toxicity. [ A 13
- week feeding study i n 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 f or females. The lowest observed adverse effect level (L O AEL) is 1,000 mg/kg/day f or males and 1,467 mg/kg/day f or females based on decreased body w eight gains in males and females (17.6 and 18.7%, respectivel y). 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 12 000 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); 3 58 mg/kg/day

(female). The LOAEL is4

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

- ye ar 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

bas ed 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 kidney s at 513 mg/kg/day (males) and 469 mg/kg/day (females), the highest dosages tested (HDT). Chronic Feeding/Oncogenicity

- Rats: A chronic feeding/carcinogenicit y 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 hy perplasia 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 obs erved in rats. Oncogenicit y - Mice: A carcinogenic study in mice fed dosages of 0, 37.5, 150, 600, and 1 200 mg/kg/day

resulted in no carcinogenic effects observed under the conditions of the study up to and including 1 200 mg/kg/day (HDT) and a s ys temic 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 day s ( 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 tox icology
. [ 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 60 0 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 onl y found in in the feces (0.45% and 12.45% of the dose for the low and high dose respectively). The remaining characterized and i dentified 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 , th e oral LD50 was found to be greater than 2000 mg/kg bw.5

A 90D feeding stud y 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 thy roid targe t 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 s ys tem.] 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 expo sure assessment was conducted using all currentl y established tolerances and the proposed new import tolerance for canola. ] i. Food. [ Acute Dietary Exposure Assessment : The US EPA has determined that an acute dietary

assessment for quinclorac is only requir ed 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, 1 998) 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 safet y factor is 1. The resulting acute Population Adjusted Dose (aPAD) is 2.0 mg/kg bw/day . The results from the acute asse ss ment 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 Eval uation Module (DEEM

- FCID) software. The chronic NOAEL is 37.5 mg/kg bw/day and the FQPA safet y factor is 1. The resulting chronic Population Adjusted Dose ( c PAD) is 0.375 mg/kg bw/day . The results from the chronic assessment showed that chil dren ages 1

–2 years old were the most highl y expos ed sub

- population. The food and water exposure utilized 3.1% of the cPAD. Table 1 below shows the chronic exposure for all sub

- populations.6

**Table 1**  **. Results**  **for Quinclorac**  **( BA** **S 514**  **H) Chronic**  **Dietary Exposure**  **An aly** **sis 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 ye ar old) 0.0099 2.65 Children (1

- 2 years old) 0.0117 3.13 Chil dren (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+ y ears old) 0.0042 1.13 Females (13

- 49 years old) 0.0043 1.16 ] ii. Drinking water
. [ The pro posed 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, re spectivel y. 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/k g 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 T able 2 below. Table 2 . Residential Exposure and Risk Estimates for Post

- Application Incidental Oral Exposure of Toddlers to Quinclorac on Turf.

**Sc en**  **ar io**  **Ex ps**  **oure mg**  **/k g**  **bw /d**  **ay Short**  **- an**  **d**

**In te**  **rm ed**  **ia te**  **-**

**T er**  **m MOE**  Hand-t o-m out h 0. 011 6364 Obj ec t- to -m out h 0. 0028 25000 To ta l 0. 0138 5072 Acute Aggregate Exposure (Food and Drinking Water) The aggregate acute risk includes residues of quinclorac from food and water
. Exposures7

from residential uses are not included in the acute aggregate assessment. The results demonstrate that there are no safet y concerns for any subpopulation based on established and new uses, and that the results clearl y meet the FQPA standard of reasonable certainty of no harm. Short

- and Intermediate

- T erm 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. T he aggregate MOE from food, water, and residential oral exposure for children 1

–2 years old is 2700 . Th is 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 concern s for an y 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 reg istered active ingredient that is structural ly

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 .]