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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION

MEMORANDUM

Date: 2-JULY-2013 

SUBJECT: Imazapyr: Petition for the Establishment of Import Tolerances on GeneticallyModified (GM) Soybean, Rapeseed subgroup 20A, Sunflower Subgroup 20B and 

Lentils

PC Code: 128821 DP Barcode: 384035, 403741

Decision No.: 440569, 466036 Registration No.: 172267

Petition No.: OE7793, 2E8045 Regulatory Action: Tolerance without U.S. 

Registration

Risk Assessment Type: Single 

Chemical/Aggregate

Case No.: 3078

TXR No.: None CAS No.: 81334-34-1

MRID No.: None 40 CFR: §180.500

FROM: Mohsen Sahafeyan, Chemist/Risk Assessor

Nancy McCarroll, Toxicologist

Bridgett Bobowiec, Biologist

Risk Assessment Branch VI

Health Effects Division (7509P)

THROUGH: Felecia Fort, Branch Chief

Risk Assessment Branch VI

Health Effects Division (7509P)

TO: Hope Johnson and Kable Davis

Fungicide Branch

Registration Division (7505P)

This document provides the Health Effects Division (HED) human health assessment for the 

proposed establishment of tolerances without U. S. registration for the herbicide imazapyr on 

imported GM soybean, rapeseed subgroup 20A, sunflower subgroup 20B and lentil. The field 

trials were conducted on the GM crops with the following BASF names: soybean of Cultivance®
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Production System, Clearfield® Canola, Clearfield® Sunflower, and Clearfield® Lentils. HED 

notes that some of the formulations used in the field trials contain other active ingredients 

(imazapic and imazamox) which are addressed in separate documents.

Introduction

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

pyridinecarboxylic acid] is a broad-spectrum, imidazolinone herbicide used for pre- and postemergence control of annual and perennial grass and broadleaf weeds, brush, vines, and 

deciduous trees in occupational and residential settings. Imazapyr is currently registered to 

BASF Corporation for use on non-cropland areas and on imidazolinone-resistant field corn. 

BASF has requested import tolerances without U. S. registration for residues of imazapyr on 

imidazolinone-tolerant soybean of Cultivance® Production System, rapeseed subgroup 20A, 

sunflower subgroup 20B and lentil. The BASF tolerance request triggered a review of the 

imazapyr toxicity database and endpoints for risk assessment. In September of 2012, the HED 

imazapyr review team called for a meeting of Hazard and Science Policy Council (HASPOC) to 

revisit the toxicity of imazapyr and determine whether a quantitative risk assessment is needed. 

After reviewing the available toxicology database for imazapyr, HASPOC concluded, with 

reasonable certainty that there is no hazard identified for imazapyr in the available database and

that dietary, residential, and occupational exposures to imazapyr do not pose a significant human 

health risk and, therefore, risk assessments are not needed. 

BASF is proposing the following tolerances on the food commodities as shown below. 

Commodity Proposed Tolerance (ppm) 

Soybean, seed 4.0

Soybean, meal 4.5

Rapeseed subgroup 

20A 

0.05 

Sunflower subgroup

20B

0.05 

Lentil 0.2 

Proposed Use

Soybean: BASF has requested import tolerances for residues of imazapyr on imidazolinone -

tolerant soybean of Cultivance® Production System from Brazil using Soyvance® (soluble extract 

formulation with 48.0% m/v imazapyr) at 0.064 lb ai/A per application and Cultifix® (waterdispersible granulesformulation (WDG) with 52.5% m/m imazapyr and 17.5% m/m imazapic) at 

maximum 0.047 lb ai/A per application on soybean. The use pattern is one post-emergence foliar 

application per season. The proposed PHI is 60 days. The submitted field trials were conducted 

on GM soybean of Cultivance® Production System in Brazil.
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Sunflower subgroup (crop subgroup 20B): BASF has requested an import tolerance for 

residues of imazapyr on sunflower subgroup 20B crops imported from Argentina using Clearsol®

DF formulation (WDG formulation containing 80 g imazapyr) applied at maximum 0.07 lb ai/A 

(0.08 kg ai/ha) and Clearsol® Plus formulation (soluble liquid formulation of co-active 

ingredients imazapyr and imazamox with 15 and 33 g ai/L respectively) applied at maximum

0.026 lb ai/A (0.03 kg ai/ha). The use pattern is one post-emergence foliar application per 

season. The proposed PHI depends on the growth rate and is approximately 100 days. The 

submitted field trials were conducted on GM sunflower (Clearfield® sunflower).

Rapeseed subgroup (crop subgroup 20A): BASF has requested an import tolerance for 

residues of imazapyr on rapeseed subgroup 20A crops imported from Argentina using ARESTM

(also a soluble liquid formulation of co-active ingredients imazapyr and imazamox with 15 and 

33 g ai/L respectively) applied at maximum 0.008 lb ai/A (9 g ai/ha). The use pattern is one 

post-emergence foliar application per season. The proposed PHI is 60 days. The submitted field 

trials were conducted on GM canola (Clearfield® canola).

Lentil: BASF has requested an import tolerance for residues of imazapyr on imported lentils

using ARESTM applied at maximum 0.008 lb ai/A (9 g ai/ha). The use pattern is one postemergence foliar application per season. The proposed PHI is 60 days. The submitted field 

trials were conducted on GM lentil (Clearfield® lentil).

Toxicity Data and Endpoint Selection

The latest assessment of the toxicity database for imazapyr was conducted in September 2012 

(Imazapyr: Summary of Hazard and Science Policy Council (HASPOC) Meeting of September 

13, 2012: Recommendations on the type of risk assessment (quantitative vs. qualitative) to be 

conducted. TXR# 0056464, 2/26/13) as part of the HASPOC determination on whether a risk 

assessment was necessary because there is no hazard identified for imazapyr in the available 

database (i.e., no toxicity demonstrated in acceptable guideline studies generally up to the 

highest doses tested of 250 – 1000 mg/kg/day). Since July 2005, when the most recent 

Reregistration Eligibility Document (RED) for Imazapyr was prepared (Jarvis et al., 2005), no 

new data have been received that would warrant a change in the acute or chronic reference doses 

(RfDs), the occupational/residential toxicological endpoint selections, the uncertainty factors, or 

the FQPA Safety Factor. 

Prior to HASPOC’s deliberations, the HED’s policy was to establish toxicological endpoints for 

all pesticides in anticipation of the RED. Consequently, the Hazard Identification Assessment 

Review Committee (HIARC, 2003) chose 250 mg/kg/day and skeletal muscle effects, based on 

the imazapyr findings and analogy with imazapic, as the endpoint for the cRfD, the short-term 

and intermediate-term incidental oral exposures as well as the short-term and intermediate-term 

dermal and the short, intermediate, and long-term inhalation exposures. The data also show that 

there is no evidence of neurotoxicity, immunotoxicity, genotoxicity, or carcinogenicity. Further, 

no adverse developmental effects or adverse reproductive effects were detected in wellconducted guideline studies. 
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Viewed from a risk assessment perspective, the conservative toxicity endpoints assigned by 

HIARC amounted only to negligible exposures and risks from dietary, residential, swimming,

and occupational routes. 

Based on the above factors, the HASPOC, with reasonable certainty, concluded that dietary, 

occupational, and residential exposures to imazapyr do not pose a significant human health risk 

and, therefore, risk assessments are not needed. Although there is potential for exposure to 

imazapy, no hazard was identified from the toxicity studies. No adverse effects were observed in 

the submitted toxicological studies regardless of the route of exposure or the species tested. 

Therefore, risk assessments are not required. Furthermore, according to the present HED 

policies, the toxicology database is considered to be adequate and no additional studies are 

required.

Residue Data

Detailed review of residue chemistry data were not conducted and are not needed because of 

HASPOC’s determination of low/no risk associated with exposure to imazapyr. Adequate field 

residue data in South America and in NAFTA regions were submitted for GM canola, GM 

sunflower and GM lentil. Field trials for soybean were conducted in South America only. 

Except for lentil, most if not all of the residues from GM soybean, GM canola, and GM 

sunflower were below the limit of quantitation (<LOQ) of the analytical method. However, if in 

future, BASF requests tolerances for residues of imazapyr on other GM crops or the same crops 

with different types of genetic modifications, adequate rational and information should again be 

provided to show that the metabolic pathways in non-tolerant and tolerant plants are comparable. 

Analytical Methods

FDA multi-residue methods do not exhibit sufficient detectability and sensitivity to other 

imidazolinone herbicides, and thus there is no reasonable expectation that these methods would 

prove to be useful for determining residues of imazapyr.

BASF has recommended new enforcement methods, BASF method SOP-PA.0288 for GM 

soybeans seed, oil, flakes and meal and BASF Method M 3519-Modified for Rapeseed subgroup 

20A, Sunflower Subgroup 20B and Lentils; these methods are substantially similar. In both 

methods the primary solvent system is acidic methanol:water solution which was used in plant 

metabolism studies of grass, corn and soybean. Both methods are liquid chromatography with 

tandem mass spectrometric detection (LC/MS/MS). The limit of quantitation (LOQ) for BASF 

method SOP-PA.0288 is 0.01 ppm and for BASF Method M 3519-Modified is 0.05 ppm.

Radiovalidation (for both methods) and independent-method validation (for M 3519-Modified) 

studies were not submitted and not required because (1) the solvent system (acidic 

methonal:water ) in the recommended methods (SOP-PA.0288 and M 3519-Modified) are 

similar to what was used in plant metabolism studies and (2) acceptable method validation data 
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were submitted for both methods. A confirmatory method is also not required since both 

methods have acceptable method validation and/or include second mass transition.

HED concludes that the submitted LC/MS/MS methods, Method SOP-PA.0288 for imazapyr 

residues in GM soybeans seed, oil, flakes and meal and Method M 3519-Modified for imazapyr 

residues in Rapeseed subgroup 20A, Sunflower Subgroup 20B and Lentils (BASF) are adequate 

for data collection and tolerance enforcement. A summary of each method is provided in 

Attachment 2.

The enforcement methods for grass forage and grass hay is method M3184, for meat and meat 

byproduct is method M 3184 and for milk is method M 3075; these methods were previously 

established.

Aggregate and Occupational Risks

HASPOC in September 2012, concluded with reasonable certainty that dietary, occupational and 

residential exposures to imazapyr do not pose a significant human health risk and, therefore, risk 

assessments are not needed. 

Imazapyr risk assessments which were conducted previously showed that there are not 

significant risks from dietary (food + water), residential, swimming and occupational exposure 

routes. The last chronic dietary exposure assessment for food and water (Donovan, W., 

D288806, 3/26/2003) resulted in <1% of the chronic population adjusted dose (cPAD) for the 

U.S. population and all population subgroups. Since imazapyr is also registered as an aquatic 

herbicide, a swimmer’s assessment was carried out resulting in incidental ingestion and dermal 

exposure MOE estimates ranging from 68,000 to 1,000,000. Similarly, a screen of the turf uses, 

analyzed as described in the new SOPs, shows MOEs in a range comparable to the swimmer’s 

scenario except for dermal which is being driven by a default conservative 100% dermal 

absorption factor. 

An acute dietary exposure and risk assessment was not conducted because a toxicological 

endpoint attributable to a single dose has not been identified for imazapyr. Similarly, no cancer 

assessment was conducted because imazapyr has been classified as a “Category E Chemical” 

(adequate evidence of no carcinogenicity in two species) which was confirmed (TXR# 0051943,

May 22, 2003). 

HED concludes that the proposed uses of imazapyr on imported soybean, rapeseed crop 

subgroup 20A, sunflower crop subgroup 20B and lentil will not result in significant aggregate

and occupational exposures and risk estimates.

Adequacy of the Proposed Tolerances

The BASF proposed tolerances and existing MRLs are as shown in the Table below.
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Commodity Proposed Tolerance (ppm) Canadian MRL

Soybean, seed 4.0

Soybean, meal 4.5

Rapeseed subgroup 

20A 

0.05 0.05 

seeds (borage, cuphea, 

echium, flax, gold of pleasure, 

hare's ear mustard, milkweed, 

mustard seed (oilseed type), 

oil radish, poppy, rapeseed 

(canola), sesame, sweet rocket

Sunflower subgroup

20B

0.05 

Lentil 0.2 0.2 

dry lentil

There are Canadian MRLs on rapeseed and lentil which are at the same levels as the proposed 

tolerances for those crops; the Canadian residue definition is also the same as that of U. S. No 

other international or Codex maximum residue limits (MRLs) exist for any other imazapyr 

registered or proposed uses. 

Based on toxicity considerations, the HASPOC concluded that there are no risk concerns from 

exposure to imazapyr. Therefore, an exemption from the requirement of a tolerance would be 

appropriate for imazapyr if there were no tolerances on other crops. In addition, lack of 

tolerance would provide trade irritation since there are existing MRLs on some crops. HED 

therefore, concluded that tolerances need to be established. HED agrees that the proposed 

tolerance levels are appropriate and also harmonize with Canadian MRLs. 

Conclusions

The toxicity database for imazapyr is considered adequate; no additional toxicological studies are 

required. The available toxicity studies (profile is attached) indicate that there are no risk 

concerns from exposure to imazapyr from dietary (food and water), residential, swimming, and 

occupational routes. Adequate residue data are available to support the proposed import 

tolerances on GM soybean, rapeseed subgroup 20A, sunflower subgroup 20B, and lentil. HED 

agrees that the proposed import tolerance levels are appropriate and also harmonize with 

Canadian MRLs. Therefore, HED has no objections to granting the proposed import tolerances

for residues of imazapyr in/on GM soybean, rapeseed subgroup 20A, sunflower subgroup 20B, 

and lentil (as shown below).

The petitioner should revise the proposed tolerance expressions for imazapyr, as follows:
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Tolerances are established for residues of the herbicide, imazapyr, including its 

metabolites and degradates, in or on the commodities in the table below. Compliance 

with the tolerance levels specified below is to be determined by measuring only the 

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

yl]-3-pyridinecarboxylic acid].

Commodity Recommended

Tolerance (ppm) 

Soybean, seed 4.0

Soybean, meal 4.5

Rapeseed subgroup 

20A 

0.05 

Sunflower subgroup 20B 0.05 

Lentil 0.20

Attachments:

Attachment 1: Supplemental Toxicology Tables

Attachment 2: Recommended Enforcement Methods
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Attachment 1: Supplemental Toxicology Tables

The toxicological data requirements (40 CFR 158.340) for food uses for imazapyr are listed in

Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline 

protocols were used. 

Table 1. Test Guideline

Technical

Required Satisfied1

870.1100 Acute Oral Toxicity .......................................................

870.1200 Acute Dermal Toxicity...................................................

870.1300 Acute Inhalation Toxicity ..............................................

870.2400 Primary Eye Irritation ....................................................

870.2500 Primary Dermal Irritation...............................................

870.2600 Dermal Sensitization ......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rat and mouse) ...................................

870.3150 Oral Subchronic (dog)....................................................

870.3200 21/28-Day Dermal (rat)..................................................

870.3250 90-Day Dermal...............................................................

870.3465 28-Day Inhalation ..........................................................

yes

yes

yes

no

no

yes

yes

yes

---

---

870.3700a Developmental Toxicity (rat).........................................

870.3700b Developmental Toxicity (rabbit)....................................

870.3800 Reproduction (rat)..........................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rat) ....................................................

870.4100b Chronic Toxicity (dog)...................................................

870.4200a Carcinogenicity (rat) ......................................................

870.4200b Carcinogenicity (mouse)................................................

870.4300 Chronic/Carcinogenicity (rat) ........................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial .....................

870.5300 Mutagenicity—Gene Mutation - mammalian ................

870.5375 Mutagenicity—Structural Chromosomal Aberrations ...

870.5395 Mutagenicity—Mammalian Erythrocyte Micronucleus.

870.5450 Mutagenicity—Rodent dominant lethal assay 

870.5500 Mutagenicity— Bacterial DNA Damage or Repair Test

870.5550 Mutagenicity—Unscheduled DNA Synthesis.................

yes

yes

yes

yes

no

no

no

yes

yes

yes

see footnote 1

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity. (hen) ..............................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotoxicity Screening Battery (rat)..................

870.6200b 90 Day Neurotoxicity Screening Battery (rat) ...............

870.6300 Developmental Neurotoxicity (rat) ................................

no

no

yes

yes

no

---

---

yes

yes

see footnote 1

870.7485 General Metabolism (rat)...............................................

870.7600 Dermal Penetration, in vivo (male rat) ...........................

yes

no 

yes

yes

870.7800 Immunotoxicity (rat and mouse)........................... yes see footnote 1
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Table 1. Test Guideline

Technical

Required Satisfied1

Non-Guideline: Comparative dermal absorption, in vitro (rat 

 and human skin)

no --

1 According to the present HED policies, the toxicology database is considered to be adequate and no additional studies are required. This is 

because, HASPOC confirmed that the available data do not suggest that there is a concern for neurotoxicity, immunotoxicity, genotoxicity, or 

carcinogenicity (Imazapyr: Summary of Hazard and Science Policy Council (HASPOC) Meeting of September 13, 2012: Recommendations on 

the type of risk assessment (quantitative vs. qualitative) to be conducted. TXR# 0056464, 2/26/13). 

Table.2: Acute Toxicity of Imazapyr Technical Grade Active Ingredient (TGAI)

Guideline No/Study Type MRIDs Results Toxicity Category

870.1100 Acute Oral 41551002 (1990)

93048016 (1990)

LD50 = > 5000 mg/kg IV

870.1200 Acute Dermal 41551003 (1990)

93048017 (1990)

LD50 = >2000 mg/kg III

870.1300 Acute Inhalation

TXR# 0006998

00132032 (1983)

93048018 (1990)

LC50 = >1.3 mg/L (gravimetric)

> 5.1 mg/L (nominal)

III

870.2400 Primary Eye Irritation/NZW 

rabbit

41551001 (1990)

93048019 (1990)

2/6 rabbits with corneal opacity 

at 21 days; discharge in 1/6 

rabbits at 21 days; 

vascularization of cornea in 1/6 

rabbits at 21 days;

Irreversible Eye Damage

I

Tested with 99.3% 

technical fine 

powder

870.2400 Primary Eye Irritation/NZW 

rabbit

Accession# 

252004

Corneal opacity cleared within 

72 hours; conjunctivitis 

reversible by day 7 

III

Tested with 93% 

technical

870.2500 Primary Skin Irritation 41551004 (1990)

93048020 (1990)

non-irritating to slight erythema 

and edema

IV

870.2600 Dermal Sensitization 00131607 (1983)

93048021 (1990)

Negative -
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Table 3: Toxicity Profile of Imazapyr Technical.

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification/Doses

Results

870.3100

90-Day oral toxicity

rodents (rat)

42774401 (1992)

Acceptable/guideline

0, 15,000, or 20,000 ppm 

(equivalent to 0, 1248, or 

1695 mg/kg bw/day in 

males and 0, 1423 or 1784 

mg/kg bw/day in females).

NOAEL =1,695 mg/kg/day for males and =1,784 

mg/kg/day for females (HDT). 

LOAEL = None.

870.3200 

21/28-Day dermal toxicity

(rabbit)

00131609 (1983)

93048022 (1990)

Acceptable/guideline

0, 100, 200 or 400 

mg/kg/day, 6 hrs/day for 5 

d/week during a 21-day 

period.

NOAEL =400 mg/kg/day (HDT). 

LOAEL = None.

870.3700a

Prenatal developmental 

toxicity in rodents

(rat)

00131611 (1983)

93048023 (1990)

Acceptable/guideline

0, 0, 100, 300 or 1,000 

mg/kg/day from days 6 

through 15 of gestation. 

Maternal NOAEL = 300 mg/kg bw/day. LOAEL 

=1,000 mg/kg bw/day, based on salivation.

Developmental NOAEL =1,000 mg/kg/day. This 

was the HDT; therefore, there is no LOAEL.

870.3700b

Prenatal developmental 

toxicity in nonrodents

(rabbit)

00131613 (1983)

93048024 (1990)

Acceptable/guideline

0, 25, 100, or 400 

mg/kg/day from days 6 

through 18 of gestation. 

Maternal NOAEL =400 mg/kg bw/day This was 

the HDT; therefore, there is no LOAEL.

Developmental NOAEL =400 mg/kg bw/day. 

This was the HDT; therefore, there is no LOAEL.

870.3800

Reproduction and fertility 

effects

(rat)

41039505 (1987)

Acceptable/guideline

0, 1,000, 5,000 and 10,000 

ppm in the diet 

(equivalent to 0, 74.2, 

380.5, or 738 mg/kg 

bw/day for males and 0, 

94.3, 471.2, or 933.3 

mg/kg bw/day for 

females). 

Parental systemic, reproductive and offspring

NOAEL =10,000 ppm (738 mg/kg bw/day in 

males 933.3 mg/kg bw/day in females). This was 

the HDT; therefore, there is no LOAEL.

870.4100a

Chronic toxicity

(rodent)

NA; see 870.4300 NA

870.4100b

Chronic toxicity 

(dog)

41039502 (1987)

Acceptable/guideline

0, 1,000, 5,000 or 10,000 

NOAEL is =10,000 ppm (250 mg/kg/day)(HDT). 

LOAEL. = None.
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Table 3: Toxicity Profile of Imazapyr Technical.

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification/Doses

Results

ppm (equivalent to 0, 25, 

125 or 250 mg/kg/day) for 

1 year.

870.4200a

Carcinogenicity 

(rat)

NA; see 870.4300

870.4200b

Carcinogenicity 

(mouse)

41038505 (1988)

42774401 (1992)

Acceptable/guideline

0, 1,000, 5,000 or 10,000 

ppm (equivalent to 0, 126, 

674 or 1,301 mg/kg /day 

in males and 0, 151,776 or 

1,639 mg/kg /day in 

females) for 18 months. 

NOAEL =10,000 ppm (1,301 mg/kg/day in males 

and 1,639 mg/kg/day in females). This was the 

HDT; therefore, there is no LOAEL.

870.4300 Combined 

Chronic/Carcinogenicity 

(Sprague Dawley rat)

41039503 (1988)

Acceptable/guideline 1

0, 100, 5000, 10000 ppm 

(M/F: 0/0, 49.9/64.2, 

252.6/317.6, 503/638.6 

mg/kg/day)

NOAEL = 10000 ppm (M/F: 503/638.6 mg/kg/day.

LOAEL = None was shown, however a statistically 

significant (but within normal range) increase in 

BUN and a nominal decrease in body weight gain 

in males (2%)(may have approached a toxic dose) 

and a nominal increase (not statistically 

significant, pair wise) in brain astrocytomas was 

seen in females, which the CARC classified as a 

“group E chemical”, no evidence of 

carcinogenicity in mice or rats. A 90-day study in 

rats showed no adverse effects at levels including 

the limit dose of 20,000 ppm (1000 mg/kg/day). 

870.5100

Bacterial reverse mutation 

(Ames Assay)

00131615 (1983) 

93048025 (1990) 

Acceptable/guideline

Negative up to 5,000 μg/plate.

870.5300

In vitro mammalian cell gene 

mutation

00151641 (1984)

93048028 (1990)

Acceptable/guideline

Negative up to cytotoxic doses (5,000 μg/mL) with 

and without activation.

870.5375 00151640 (1984) Negative up to cytotoxic doses (5,000 μg/mL) with 
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Table 3: Toxicity Profile of Imazapyr Technical.

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification/Doses

Results

In vitro mammalian 

chromosome aberration 

(CHO)

93048026 (1990)

Acceptable/guideline

and without activation.

870.5550

Unscheduled DNA synthesis 

(RPH)

00151639 (1984)

93048027 (1990) 

Acceptable/guideline

Reported as negative (unacceptable, 1989), but 

considered acceptable in 1997. 2

870.5450

Rodent Dominant Lethal

00151638 (1985)

Acceptable/guideline

Reported as negative (unacceptable, 1989), but 

considered acceptable in 1997. 2

870.6200a

Acute neurotoxicity 

screening battery (rat)

48469001 (2011)

Acceptable/guideline

0, 200, 600 mg/kg

NOAEL =≥2000 mg/kg (HDT); therefore, there is 

no LOAEL

870.6200b

90 Day neurotoxicity 

screening battery (rat)

48469001 (2011)

Acceptable/guideline

0, 300, 1000 mg/kg/d

(0, 89, 272, 924 mg/kg/d 

♂; 0 92, 283, 933 mg/kg/d 

♀)

NOAEL ≥924 mg/kg/d (♂); ≥933 mg/kg/d (♀) 

(HDT); therefore, there is no LOAEL
Page 13 of 15

Table 3: Toxicity Profile of Imazapyr Technical.

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification/Doses

Results

870.7485

Metabolism and 

pharmacokinetics

(rat)

43861501 (1994)

Acceptable

M&F: unlabeled or 

labeled imazapyr ~ 9.5 

mg/kg or 924 mg/kg 

single gavage dose or as 

14-daily doses of 

unlabeled imazapyr 

followed by single labeled 

dose of 9.26 mg/kg.

M&F: 10 mg/kg labeled 

imazapyr single gavage 

dose to measure excretion 

via expired air (pilot 

study). 

M&F: 9.94 mg/kg labeled 

imazapyr by intravenous 

injection.

No sex-related differences in absorption were 

apparent. Within 48 hours of treatment, >90% of 

the administered dose was recovered in the excreta 

suggesting that elimination of the labeled test 

material was rapid. No specific sequestering 

tissues or organs were identified. Seven days after 

treatment, essentially all the test material had been 

eliminated. Rats that received the test material by 

intravenous injection excreted 87-95% of the 

administered dose in the urine and approximately 

6% into the feces. This suggests that 15-28% if the 

oral administered dose recovered in the feces 

represents unabsorbed material. 

Metabolite characterization studies show that 

essentially all of the test material was excreted 

unchanged. Two minor metabolites CL 252,974 

and CL 60,032 were detected in the urine or feces 

of treated rats; however, their contribution

combined was <0.5% of the administered dose. 

Up to 12 additional unidentified metabolites were 

isolated, but they constituted <3% of the 

administered dose. Based on the results, the study 

author suggests that what limited metabolism of 

CL 243,997 occurs, proceeds through hydrolysis 

to form the 2-carbonyl derivatives: CL 252,974 

and CL 60,032.

870.7600

Dermal penetration

NA NA

870.7800

Immunotoxicity

48490102 (2011)

Acceptable/guideline

0, 500, 1500, 5,000 ppm 

(equivalent to 0, 155, 525

or 1,668 mg/kg /day in 

female mice)

NOAEL = ≥1,668 mg/kg/day; LOAEL was not 

established.

1 The study is acceptable for regulatory purposes according to documentation in TXR# 0011692 (1995), TXR# 

0051943 (2003), and TXR# 0011213 (1994). 

2 Memorandum, dated 3/10/97, from Steve Robbins et al. of HED to Phillip Errico RD. 
Page 14 of 15

Attachment 2: Recommended Enforcement Methods

BASF petitioned for imazapyr on GM soybean in September 2010 and proposed method SOPPA.0288 as the enforcement method. In May of 2011, BASF petitioned for imazapyr on rapeseed 

crop subgroup 20-A, sunflower crop subgroup 20-B and lentils and proposed method 3519-

modified as the enforcement method. Although the methods have different numbers, method 

M3519-modified and method SOP-PA.0288 are very similar.

Method SOP-PA.0288: References: MRIDs: 48251006-7, 48793802 and 48824802

Method SOP-PA.0288 is used for determination of imidazolinone residues (imazapyr, imazapic 

and its metabolites) in several matrices and processed fractions (Sugarcane, sugar, molasses, 

sunflower seed, sunflower oil, soybean grain, flaked soybean, soybean meal, soybean toasted 

meal, soybean oil)

Briefly, samples of the fortified soybean matrices were extracted with methanol:water:HCl 1 

mol/L (60:39:1, v/v/v) on a mechanical shaker for 10 minutes. The extract was centrifuged for 5 

minutes at 3000 rpm and an aliquot was taken into 5 mL volumetric flask. The volume was 

filled to the mark with a solution of 0.1% formic acid in water:0.1% formic acid in methanol 

(1:1, v/v). The solution was filtered, when necessary, and all samples were then quantified by . 

Two characteristic mass transitions (262.0 → 217.1 m/z and 262.0 → 149.1 m/z) were used to 

monitor imazapyr in each of the soybean matrices. 

Acceptable method validation data were submitted. The limit of quantitation (LOQ) was 

established as 0.01 ppm. 

BASF Method M3519-Modified

References: MRIDs 48793801, 48793804-6, and 4882501

BASF method M3519 is fully described in the independent laboratory validation report BASF 

Reg Doc ID 2002/5004302 (MRID: 48793801). 

The summary of method M3519 with the modifications listed is as follows:

Residues of imazamox (BAS 720 H), imazapyr (BAS 693 H) and hydroxymethyl metabolite (CL 

263,284) are extracted using an acid methanol-water solution (40 mL 1N hydrochloric acid 

solution + 1560 mL purified water + 2400 mL methanol). The extract is centrifuged and an 

aliquot is taken and diluted with either Mobile phase A:Mobile phase B (50:50 V/V) (lentils) or 

acidic water solution (water + 0.1% formic acid) (canola and sunflower) for analysis by 

LC/MS/MS.

The final solution for the samples was either 50/50 v/v Mobile Phase A and Mobile Phase B:

Mobile Phase A – 1 mL formic acid in 1000 mL water
Page 15 of 15

Mobile Phase B – 1 mL formic acid in 1000 mL methanol

Or acidic water solution (0.1% formic acid in water – no PH stated).

Lentils and some of the canola seeds were diluted in the Mobile Phase A + Mobile Phase B.

Sunflower seed, sunflower oil and meal, some of the canola seeds and canola meal and oil were 

diluted in the acidic water solution.

Formic acid was substituted for glacial acetic acid in the HPLC mobile phases in all three 

studies, for all matrices as follows:

Mobile Phase A – 1 mL formic acid in 1000 mL water

Mobile Phase B – 1 mL formic acid in 1000 mL methanol

The following mass transitions were used for canola, lentil and sunflower matrices (including 

process fractions):

Matrix / Commodity Validation Samples Field and Procedural 

Recovery Samples

Reference

Canola seed

Canola meal

Canola oil

262/217

262/149

262/217 2008/7019227 

(MRID 48793805)

Lentil seed N/A 262.2/217.2 2008/7019226

(MRID 48793804)

Sunflower seed

Sunflower meal

Sunflower oil

262.2/217.2 262.2/217.2 2008/7019225

(MRID 48793806)

Acceptable method validation data were submitted. The limit of quantification (LOQ) of the 

method is 0.05 mg/kg for imazamox (BAS 720 H), CL 263,284 and imazapyr (BAS 693 H).