EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division Contact: James Tompkins; 703-305-5697

BASF Corporation

0E7793

EPA has received a pesticide petition (0E7793) 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 180.500 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 soybean at 4.0 parts per million (ppm) and in or on the 

processed commodity soybean meal at 4.5 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. i. Bermuda grass. Radiolabelled imazapyr (pyridine-6-

14Cimazapyr), 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.

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 
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accounted for insignificant proportions of the residue below 10% TRR. Thus, the study 

demonstrates that imazapyr is the only relevant residue in clover.

2. Analytical method. The proposed analytical method for detecting residues of 

imazapyr in soybean seed and processed fractions is an LC-MS/MS method. This 

validated method has an LOQ of 0.01 mg/kg.

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. Soybeans. Imazapyr was applied at the proposed

labeled rate in 8 field trials in Brazil. Residues of imazapyr ranged from <0.05 to 2.0 

mg/kg in samples taken 60 days after treatment. Three of the trials also incorporated 

residue decline samples taken at 40, 60, 80, 100, and 120 days after treatment. No 

residues were determined 120 days after treatment.

The formulation BAS 714 01 H, containing the active ingredients imazapyr and imazapic, 

was applied according to labeled rates in 8 field trials in Brazil. Residues of imazapyr 

ranged from <0.05 to 3.0 mg/kg in samples taken 60 days after treatment. Three of the

trials also incorporated residue decline samples taken at 40, 60, 80, 100, and 120 days 

after treatment. No residues were determined 120 days after treatment.

A processing study was conducted using soybeans from two trials in Brazil, applied at 

two times and three times the proposed application rate. The soybean samples were 

taken 60 days after treatment and processed into fractions (flake soybean, oil, meal, and 

toasted meal). The mean transfer factors for soybean commodities demonstrate that 

imazapyr residues do not result in the soybean oil, but concentrate into flaked soybean, 

meal and toasted meal.

Another processing study was conducted using soybeans from two trials in Brazil. A 

single treatment of BAS 714 01 H, containing imazapyr and imazapic was applied at two 

times and three times the proposed application rate. The soybean samples were taken 60 

days after treatment and processed into fractions (flake soybean, oil, meal, and toasted 

meal). The mean transfer factors for soybean commodities were 0.75, <0.04, 1.34 and 

1.15 for flake soybean, oil, meal, and toasted meal, respectively.

Soybean hulls and aspirated grain fractions were not analyzed in either processing study. 

However, it is not anticipated that a significant amount of soybean hulls or aspirated 

grain fractions from genetically modified soybeans would be used as animal feed items. 

Additionally, soybean hulls and aspirated grain fractions are blended commodities and 

therefore any imazapyr treated soybean hulls and aspirated grain fractions would be 

blended with other untreated soybean hulls and aspirated grain fractions before being fed 

to cattle. Based on the limited import of genetically modified soybeans from Brazil and 

the blended nature of these commodities, any potential imazapyr residues would be 
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diluted and can be considered de minimus.

Furthermore, inclusion of potential imazapyr residues in the blended commodities of 

soybean hulls and aspirated grain fractions would not significantly add to the estimated 

dietary burden for cattle. The new estimated dietary burden for dairy cattle, under the 

maximally reasonably balanced diet (MRDB) guidance (updated in 2008) and including 

soybean seeds and meal at tolerance-level residues results, is 18.5 mg/kg imazapyr. 

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. 

Soybean hull residues would have to be higher than 65 mg/kg in order to result in a 

dietary burden of 24 mg/kg for dairy cattle under the MRDB guidance. Aspirated grain 

fractions are not used in the dairy cattle diet (i.e., the basis for the existing meat and milk 

tolerances), and they constitute only 5% of the beef cattle diet. The updated dietary 

burden for beef cattle is 0.8 mg/kg using the MRDB guidance, in comparison to the new 

dietary burden of 18.5 mg/kg for dairy cattle and, therefore, it is exceedingly unlikely that 

residues in aspirated grain fractions would lead to a beef cattle diet with higher imazapyr 

residues than the dairy cattle diet. Consequently, soybean hulls and/or soybean aspirated 

grain fractions containing imazapyr residues are unlikely to result in potential beef and 

dairy cattle dietary burdens in excess of the 24 mg/kg basis for the existing meat and milk 

tolerances.

ii. 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 in kidney averaged 0.25 mg/kg. 

The estimated dietary burden under current guidance is 18.5 ppm in dairy cattle including 

soybean seeds and 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 soybeans will not require any changes to the current meat and milk 

tolerances.

B. Toxicological Profile

1. Acute toxicity. Based on a battery of acute toxicity studies, imazapyr has been 

placed in toxicity category I for eye irritation, category IV for oral LD50 and primary 

dermal irritation, and category III for dermal LD50 and inhalation LC50. Imazapyr was a 

non-sensitizer when tested for dermal sensitization (Buehler Method).

2. Genotoxicty. Studies on gene mutation and other genotoxic effects, Ames 

Salmonella Assay, CHO/HGPRT Point Mutation Assay, in vitro CHO cell chromosome 

aberration assay, dominant lethal assay, and unscheduled DNA synthesis (UDS) in 

primary rat hepatocytes yielded negative results.

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

study at doses of 0, 100, 300, or 1,000 mg/kg 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 
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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 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) (738 mg/kg 

b.w./day for males, 933.3 mg/kg b.w./day for females, as based on food consumption 

data).

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 HCT (approximately 1,695 mg/kg 

b.w./day for males, 1,785 mg/kg b.w./day for females, as based on food consumption 

data).

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

resulted with the NOAEL of 400 mg/kg b.w./day 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 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 HCT (approximately 500 mg/kg b.w./day for males, 640 mg/kg b.w./day for 

females, as based on food consumption data).

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 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. Results from a rat metabolism study indicated that imazapyr was rapidly absorbed and 

excreted by 7 days post-dosing, with the majority of the administered 14C-label (90%) 

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.
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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, 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–month) studies, 

indicate that imazapyr is not associated with any treatment-related 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 soybeans 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. For this Tier 1 analysis, tolerance values were used for soybean at 4.0 mg/kg; 

grass, hay at 30 mg/kg; grass, forage at 100 mg/kg, field 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; 

other meat byproducts of cattle, sheep, goats, and horses at 0.05 mg/kg; meat of cattle, 

sheep, goats, and horses 0.05 mg/kg; fat 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 
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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 0.4% of the chronic 

RfD. Exposure estimates for infants, the most highly exposed subpopulation, were only 

0.011012 mg/kg b.w./ day (or 0.4% of the RfD). Therefore, the results of the chronic 

dietary assessment demonstrate a reasonable expectation 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 

soybean tolerance. 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 

soybeans will result in aggregate exposures with reasonable certainty of no harm.

D. Cumulative Effects 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 

soybean application will utilize approximately 0.4% of this value. Exposure estimates for 

the general U.S. population were only 0.003891 mg/kg b.w./day or 0.16% of the RfD. 

Exposure estimates for infants, the most highly exposed population group, were only 

0.011012 mg/kg b.w./day or 0.4% 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 
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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 data base 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 soybeans and the granting of the requested 

tolerances.

F. International Tolerances

There are no Codex tolerances established for imazapyr on soybeans.