EPA REGISTRATION DIVISION 

COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN 

THE FEDERAL REGISTER 

EPA Registration Division contact: Kable Bo Davis (703)306-0415

BASF Corporation

2E8045

EPA has received a pesticide petition (2E8045) from BASF Corporation, 

26 Davis Drive, Research Triangle Park, NC 27709 proposing, 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 180.490 by establishing a tolerance for residues 

of imazapyr 2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-]H-imidazol-2-yl]-3-

pyridinecarboxylic acid in or on the raw agricultural commodity on Crop subgroup 

20A - Rapeseed subgroup at 0.05 parts per million (ppm), Crop subgroup 20B –

Sunflower subgroup at 0.05 parts per million (ppm) and lentils at 0.2 parts per 

million (ppm). 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. The metabolic pathway of imazapyr is understood 

and is similar in a range of different crops including Bermuda grass, 

Imidazolinone-Resistant Corn, Clover and soybean. Parent imazapyr was

identified as major component of the total residue.

i. Bermuda grass. Radiolabelled imazapyr (pyridine-6-

14C-imazapyr), was applied 

to established Bermuda grass. A single application was made at the nominal 

rate of 1.5 lbs a.i./A. Samples of Bermuda grass were collected for analysis at 0, 

4, 10, 15, and 21 days after treatment. The majority of residues were extracted 

with acidified methanol (86 - 97% TRR). The predominant residue, accounting for 

78 to 97% TRR, was the parent compound, imazapyr. Metabolites CL 240000 and 

CL 247087 each accounted for ≤ 10%TRR while CL 9140 was present at a 

maximum of 12% TRR. The study demonstrated that imazapyr is metabolised 

slowly in Bermuda grass and the major residue in the foliage is imazapyr.

ii. Imidazolinone-Resistant Corn. Radiolabeled imazapyr was applied once to 

maize plants in two plots at 0.025 lb a.i./A and 0.071 lb a.i./A. Imazapyr was the 

only major residue found in maize grains or in plants of different growth stages. 

Any metabolite observed was only present at insignificant concentrations in 

samples taken after the day of application. Thus, imazapyr is the only relevant 

residue in maize. Additionally, extraction of maize oil with hexane showed that 

residues of imazapyr did not accumulate in that lipophilic matrix.
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iii. Clover. Radiolabeled imazapyr was applied once as an aqueous solution to 

established clover at 1.5 lb a.i./A (1680 g a.i./ha). Imazapyr was the major 

residue in clover plants, accounting for 68 to 99% TRR. Metabolites CL 9140, 

CL 240000 and CL 247087 each accounted for insignificant proportions of the 

residue below 10% TRR. Thus, the study demonstrates that imazapyr is the only 

relevant residue in clover.

iv. Soybean. Radiolabeled imazapyr was applied once as an aqueous solution to 

established CV127-9 soybean at 0.096 lb ai/A (107 g ai/ha). Imazapyr underwent 

significant metabolism; however, the parent molecule was the most abundant 

component of the residue in all matrices except straw and pods. Imazapyr is 

significantly metabolized in soybean, but no metabolites occur that would be 

metabolites of concern. Thus, the study demonstrates that imazapyr is the only 

relevant residue in soybean. 

2. Analytical method. i. Canola. The proposed analytical method for 

detecting residues of imazapyr in Canola RAC and processed commodity 

samples is an LC/MS/MS method with LOQ of 0.05 ppm. 

ii. Lentils. The proposed analytical method for detecting residues of imazapyr in 

lentil RAC samples is an LC/MS/MS method with LOQ of 0.05 ppm. 

iii. Sunflower. The proposed analytical method for detecting residues of imazapyr 

in sunflower RAC and processed commodity samples is an LC/MS/MS method 

with LOQ of 0.05 ppm. Another proposed method for detecting residues of 

imazapyr in sunflower RAC and processed commodity samples is also an 

LC/MS/MS method with LOQ 0.01 ppm.

iv. Animals. Enforcement methods for analysis of residues of imazapyr in animal 

commodities were included in prior submissions. M 3023 is a reliable capillary 

electrophoresis method with ultraviolet (CE/UV) detection for the determination of 

imazapyr residues in grass forage and grass hay. M 3184 is a reliable CE/UV 

method for the determination of imazapyr residues in meat, kidney, other meat 

byproducts, and fat of cattle, sheep, goats, and horses. M 3075 is a reliable 

CE/UV method for the determination of imazapyr residues in milk.

3. Magnitude of residues. i. Canola. Field trial data were generated for 

imazapyr on imidazolinone-tolerant ClearfieldTM canola with a total of 12 trials in 

NAFTA growing regions during 2008. Following a single broadcast foliar 

application of BAS 723 00 H, to canola at 9-10 g ae/ha, imazapyr residues were 

<0.05 ppm (<LOQ) in/on 24 treated canola seed samples harvested at a 68-72 

day PHI. 

A processing study was conducted using a single application of imazapyr at 45 g 

ae/ha. Imazapyr residues were 0.10 ppm in the treated meal sample and nonquantifiable (<0.05 ppm) in the treated refined oil sample, each derived from the 

seed RAC sample bearing residues at 0.07 ppm. A comparison of the residues in 

the RAC with those in the processed fractions indicated that residues of imazapyr 

do not concentrate in canola refined oil, and do not concentrated appreciably in 

meal (processing factor, 1.4x).

ii. Lentils. Field trial data were generated for imazapyr on imidazolinone-tolerant 

lentil with total of five trials in NAFTA growing regions during the 2008 season.
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Following a single broadcast foliar application of BAS 723 00 H, to lentil at 9 g 

ae/ha, imazapyr residues ranged from 0.06 to 0.10 ppm in/on ten treated lentil 

seed samples harvested at a 58-60 day PHI. 

iii. Sunflower. Field trial data from 5 trials were generated for imazapyr on 

imidazolinone-tolerant sunflower in Argentina during the 2001-2002 growing 

season. Following a single broadcast foliar application of BAS 693 05 H, to 

sunflower at rates of 80, 100 and 160 g ae/ha., imazapyr residues were <0.05 

ppm (<LOQ) in/on 3 treated sunflower seed samples and 2 treated sunflower 

flower samples harvested at a 90-100 day PHI.

A total of six trials were conducted in USA during the 2001-2002 growing season. 

Following a single broadcast foliar application of Arsenal 2AS, to sunflower at a 

rate of 0.02 lb ae/acre (22 g ae/ha), imazapyr residues ranged from <0.05 ppm 

(<LOQ) to 0.09 ppm in/on 12 treated sunflower seed samples harvested at a 72-

100 day PHI.

A total of five trials were conducted on sunflower in NAFTA Growing Regions 

during 2008. Following a single broadcast foliar application of BAS 723 00 H, to 

sunflower at 9 g ae/ha, imazapyr residues ranged from <0.05 (<LOQ) to 0.06 

ppm in/on ten treated sunflower seed samples harvested at a 58-60 day PHI.

A total of six trials were conducted on sunflower in Argentina during 2007, 2008 

and 2009. Following a single broadcast foliar application of Clearsol DF, to 

sunflower at 60 and 120 g ae/ha, imazapyr residues ranged from <0.01 (<LOQ) 

to 0.03 ppm in/on eleven treated sunflower seed samples harvested at a 98-109 

day PHI.

A total of four trials were conducted on sunflower in Argentina during 2011. 

Following a single broadcast foliar application of BAS 723 00 H, to sunflower at 

30 and 60 g ae/ha, imazapyr residues ranged from <0.01 (<LOQ) to 0.03 ppm 

in/on eight treated sunflower seed samples harvested at a 81-143 day PHI.

A total of three trials were conducted on sunflower in Uruguay and Argentina 

during 2010. Following a single broadcast foliar application of BAS 723 00 H, to 

sunflower at 80 g ae/ha, imazapyr residues were all <0.01 (<LOQ) in/on eight 

treated sunflower seed samples harvested at a 102-111 day PHI. 

A processing study was conducted using Sunflowers with imazapyr targeting 

0.02 lb ae/A (22 g ai/ha, 1X) and 0.04 lb ae/A (44 g ai/ha, 2X) in North Dakota. 

Residues of imazapyr concentrated slightly in meal (1.4X), but did not 

concentrate in refined oil. Another processing study was conducted using 

Sunflower from two trials in Canada. Imazapyr residues after a single broadcast 

foliar application of imazapyr at 46 g ae/ha, were 0.16 and 0.27 ppm. Imazapyr 

residues were 0.54 and 0.61 ppm in two treated samples of meal and were nonquantifiable in two treated samples of refined oil, each derived from the seed 

RAC samples. The residues of imazapyr do not concentrate in sunflower refined 

oil, but do concentrate in meal (processing factors 3.4x and 2.3x, average, 2.8x).

iv. Ruminants. Lactating dairy cows were dosed orally each day for 28 or 29 

consecutive days at feed equivalents of 0, 58, 157, 607, and 1,680 mg 

imazapyr/kg dry matter consumed. At 58 mg/kg, imazapyr residues in milk were 

< 0.01 mg/kg; residues in muscle, fat, and liver were <0.05 mg/kg; and residues 
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in kidney averaged 0.25 mg/kg. The estimated dietary burden under current 

guidance is 18 ppm in dairy cattle including canola and sunflower meal, which is 

lower than EPA’s 2005 dietary burden estimate of 24 mg/kg, which is the basis 

for the existing meat and milk tolerances. Therefore, the new import tolerance 

for canola, lentil and sunflower will not require any changes to the current meat 

and milk tolerances.

Canola meal and sunflower meal are used as feed items for beef and dairy cattle. 

Due to the low levels of residue in canola meal and sunflower meal, there is only 

a slight increase in dietary burden for beef and dairy cattle. EPA’s previous 

dietary burden of 24 mg/kg for beef and dairy cattle was estimated in 2005 using 

the now obsolete maximum theoretical dietary burden (MTDB) guidance. The 

current meat and milk tolerances are based on a dietary burden of 24 mg/kg.

v. Poultry. Canola meal and sunflower meal are used as feed items for poultry. 

Due to the low levels of residue in canola meal and sunflower meal, there is only 

a slight increase in dietary burden for laying hens. Based on the dietary burden of 

0.068 mg/kg in laying hens, no residues are expected in poultry commodities.

B. Toxicological Profile

1. Acute toxicity. Imazapyr has low toxicity via the oral, dermal and 

inhalation routes of exposure. It is not irritating to the skin and showed no dermal 

sensitization potential (Buehler Method). An eye irritation study demonstrated 

irreversible corneal opacity.

2. Genotoxicity. Imazapyr showed no genotoxic potential in a battery of 

studies on gene mutation (Ames Assay, CHO/HGPRT Mutation Assay) and other 

genotoxic effects (in vitro CHO cell chromosome aberration assay, dominant 

lethal assay, unscheduled DNA synthesis (UDS) in primary rat hepatocytes and 

mouse micronucleus).

3. Reproductive and developmental toxicity. i. For a rat developmental 

toxicity study at doses of 0, 100, 300, or 1,000 mg/kg body weight/day (b.w./day), 

the only clinical sign of toxicity was salivation in gravid dams at 1,000 mg/kg 

b.w./day. The No-Observed-Adverse-Effect Level (NOAEL) for maternal toxicity 

is 300 mg/kg b.w./day. There were no developmental findings in this study up to 

the limit dose of 1,000 mg/kg b.w./day, the highest dose tested (HDT).

ii. For a rabbit development toxicity study at doses of 0, 25, 100, and 400 mg/kg 

b.w./day, the maternal and developmental NOAEL is 400 mg/kg b.w./day, the 

HDT. Doses were based on pilot range-finder study, which tested at 0, 250, 500, 

1,000, and 2,000 mg/kg b.w./day. The only toxic effect observed was increased 

salivation at 1,000 and 2,000 mg/kg b.w./day.

iii. A 2–generation rat reproduction study at doses of 0, 1,000, 5,000, or 10,000 

ppm yielded a NOAEL of 10,000 ppm highest concentration tested (HCT) 

(equivalent to 738 mg/kg b.w./day for males, 933.3 mg/kg b.w./day for females).

4. Subchronic toxicity. i. A 90–day dietary study in rats at doses of 0, 

15,000, or 20,000 ppm resulted in a NOAEL of 20,000 ppm, the HCT 

(approximately 1,695 mg/kg b.w./day for males, 1,785 mg/kg b.w./day for 

females).
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ii. A 21–day rabbit dermal toxicity study at doses of 0, 100, 200, or 400 mg/ kg 

b.w./day resulted in the NOAEL of 400 mg/kg b.w./day, the HDT.

5. Chronic toxicity. i. A 1–year chronic toxicity study in dogs at doses of 0, 

1,000, 5,000, or 10,000 ppm yielded a NOAEL of 10,000 ppm, the HCT 

(equivalent to 250 mg/kg b.w./day).

ii. A 2–year chronic toxicity/ carcinogenicity study in rats at doses of 0, 1,000, 

5,000, or 10,000 ppm provided NOAELs for both systemic toxicity and 

oncogenicity of 10,000 ppm, the HCT (approximately 500 mg/kg b.w./day for 

males, 640 mg/kg b.w./day for females).

iii. An 18–month oncogenicity study in mice at doses of 0, 1,000, 5,000, or 10,000 ppm 

provided NOAELs for both systemic toxicity and oncogenicity of 10,000 ppm, the HCT 

(equivalent to 1,500 mg/kg b.w./day).

6. Animal metabolism. The rat, goat and hen metabolism studies indicate 

that the qualitative nature of the residues of imazapyr in animals is adequately 

understood. 

i. Rat. Results from a rat metabolism study indicated that imazapyr was rapidly 

absorbed and excreted by 7 days post-dosing, with the majority (90%) of the 

administered 14C-label eliminated in the urine within 48 hours. Metabolite 

characterization studies showed that essentially all the test material was excreted 

unchanged. Two minor metabolites were detected in the urine or feces of treated 

rats; however, their contribution combined was less than or equal to 0.5% of the 

administered dose. An additional 12 unidentified metabolites were isolated, but 

they contributed less than 3% of the total dose.

ii. Ruminant. Goats were dosed with radiolabeled imazapyr at 17.7, 42.5, or 47 

mg/kg dietary equivalents for 7 days. As assessed for goats receiving the 17.7 or 

42.5 mg/kg doses, TRR in fat, liver, and leg and loin muscle were nondetectable 

(<0.05 mg/kg). The TRR in milk was a maximum of 0.01, 0.02, and 0.02 mg/kg 

for the three goats, respectively, while the TRR in kidney was 0.08, 0.11, and 

0.08 mg/kg, respectively. Of these residues, parent imazapyr accounted for 50–

66% of the TRR in milk and 82–95% of the TRR in kidney. No metabolites were 

identified which require regulation. 

iii. Poultry. Hens were dosed with radiolabeled imazapyr at 0, 1.98 and 9.72 

mg/kg. TRR in the egg samples was less than the validated detection limit of 

0.01 mg/kg. Residues in blood, skin with adhering fat, muscle, liver and kidney 

tissues taken at 22 hours after the last dose were all less than the validated 

detection limit of 0.01 mg/kg. The results of this study clearly show that orally 

administered imazapyr was rapidly eliminated by the hen as unchanged parent 

compound and that imazapyr related residues do not accumulate in eggs or the 

edible tissues of poultry. Based on these metabolism results, and expected 

dietary burden in poultry, a poultry feeding study is not necessary.

7. Metabolite toxicology. There were no metabolites identified in plant or 

animal commodities which require regulation.

8. Endocrine disruption. The collective data from the 2–generation rat 

reproduction study as well as from the subchronic (90–day) rat feeding study and 

chronic feeding studies in the dog (1–year), rat (24–month), and mouse (18–
6

month) studies, indicate that imazapyr is not associated with any treatmentrelated estrogenic or endocrine effects.

C. Aggregate Exposure

1. Dietary exposure.

i. Food.

a. Acute Dietary Exposure. An acute dietary risk assessment is not required 

because no acute toxicological endpoint was identified by the EPA for imazapyr.

b. Chronic Dietary Exposure. A Tier 1 assessment of potential chronic dietary 

exposure was performed using DEEMTM for the proposed import tolerance of 

imazapyr on Crop subgroup 20A - Rapeseed subgroup (representative 

commodity rape seed canola, Crop subgroup 20B – Sunflower subgroup 

(representative commodity sunflower seed) and lentils for weed control. This 

assessment included the current tolerances as listed in 40 CFR 180.500 on 

grass hay and forage, field corn commodities, fish, shellfish, tissues of cattle, 

sheep, goats, and horses, and milk. Drinking water was also included (see 

below). For this Tier 1 analysis, tolerance values were used for rapeseed 

subgroup at 0.05 mg/kg; sunflower subgroup at 0.05 mg/kg; lentils at 0.2 mg/kg; 

corn grain at 0.05 mg/kg; fish at 1.0 mg/kg; shellfish at 0.1 mg/kg; kidney of 

cattle, sheep, goats, and horses at 0.2 mg/kg; liver, meat, fat and other meat 

byproducts of cattle, sheep, goats, and horses at 0.05 mg/kg; and milk at 0.01 

mg/kg. Chronic dietary exposure analyses for the overall U.S. population and 

population subgroups, including infants and children, were compared to the 

chronic Reference Dose (RfD) of 2.5 mg/ kg b.w./day. Results of the chronic 

dietary analyses for all population subgroups examined were at or below 0.3% of 

the chronic RfD. Exposure estimates for non-nursing infants, the most highly 

exposed subpopulation, were only 0.007152 mg/kg b.w./day (or 0.3% of the 

RfD). Therefore, the results of the chronic dietary assessment demonstrate a 

reasonable certainty of no harm from the proposed and existing uses of 

imazapyr.

ii. Drinking water. Drinking water residues were included in the dietary 

assessment at an estimated drinking water concentration (EDWC) of 79 μg/L, 

which is the maximum level estimated by EPA EFED in Tier 1 drinking water 

modeling conducted for the imazapyr RED.

2. Non-dietary exposure. A non-dietary exposure assessment was 

conducted and this assessment included the updated chronic dietary exposure 

values for the proposed rapeseed subgroup, sunflower subgroup and lentil 

tolerances. The incidental oral, dermal, and inhalation exposures were obtained 

from the EPA risk assessments conducted in 2005. Short-term residential 

aggregate MOE’s are 400 for toddlers (children 1-2 years old) and 710 for adult 

females and the U.S. population. These MOE’s demonstrate that the proposed 

import tolerance for rapeseed subgroup, sunflower subgroup and lentil will result 

in aggregate exposures with reasonable certainty of no harm. 

D. Cumulative Effects.
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Imazapyr belongs to the imidazolinone class of compounds, a class 

comprised of a number of registered herbicides. The herbicidal activity of the 

imidazolinones is due to the inhibition of acetohydroxyacid synthase (AHAS), an 

enzyme only found in plants. AHAS is part of the biosynthetic pathway leading to 

the formation of branched chain amino acids. Animals lack AHAS and this 

biosynthetic pathway. This lack of AHAS contributes to the low toxicity of the 

imidazolinone compounds in animals. We are aware of no information to indicate 

or suggest that imazapyr has any toxic effects on mammals that would be 

cumulative with those of any other chemical.

E. Safety Determination

1. U.S. population. Based on the chronic RfD of 2.5 mg/kg b.w./day, the 

proposed canola, lentil and sunflower application, in addition to the existing uses 

(tolerances), will utilize approximately 0.3% of this value. Exposure estimates for 

the general U.S. population were only 0.002006 mg/kg b.w./day or 0.1% of the 

RfD. Exposure estimates for non-nursing infants, the most highly exposed 

population group, were only 0.007152 mg/kg b.w./day or 0.3% of the RfD. EPA 

generally has no concern for exposure below 100% of the RfD which represents 

the level at or below which daily aggregate dietary exposure over a lifetime will 

not pose appreciable risks to human health. The complete and reliable toxicity 

data, indicating low potential mammalian toxicity, and the conservative chronic 

exposure assumptions support the conclusion that there is a ‘‘reasonable 

certainty of no harm’’ from aggregate exposure to imazapyr residues.

2. Infants and children. No developmental, reproductive or fetotoxic effects 

were noted at the highest doses of imazapyr tested. The only maternal effect in 

the rat teratology study was increased salivation in the highest dose group. The 

NOAEL used to calculate the RfD for the general U.S. population is 250 mg/kg 

b.w./day derived from the 1–year chronic toxicity study in dogs. That NOAEL is 

lower than the developmental NOAELs for the teratology studies in rabbits and 

rats (1.6 and 4 times, respectively), as well as lower than the NOAEL for the 2–

generation reproduction study in male and female rats (~3 - 3.7 times). EPA has 

found the database relative to prenatal and postnatal effects for children to be 

complete, valid and reliable. There were no effects observed in the offspring in 

the developmental studies in rats and rabbits. In the reproduction study, the lack 

of any pup effects observed at 10,000 ppm (the highest dose tested) in their 

growth and development from parturition through adulthood, suggests that there 

is no additional sensitivity for infants and children. Therefore, an additional safety 

(uncertainty) factor is not warranted and the RfD of 2.5 mg/kg b.w./day, which 

utilizes a 100-fold safety factor, is appropriate to assure a reasonable certainty of 

no harm to infants and children. Therefore, the registrant believes that the results 

of the toxicology and metabolism studies support both the safety of imazapyr to 

humans based on the intended use as a herbicide for imported canola, lentils 

and sunflower and the granting of the requested tolerances.

F. International Tolerances
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PMRA has proposed Canadian MRL for Lentils at 0.2 ppm and Rape seed 

(Crop subgroup 20A) at 0.05 ppm for domestic crops treated with Imazapyr. 

There are no Codex tolerances established for Imazapyr on Canola, Lentils and 

Sunflower.