### UNITED STATES ENVIRONMENTAL PROTECTION AG EN CY WASHINGTON , D

. C

. 20460



### MEMORANDUM

Date: 12-MAR-2014 OFFI CE OF C HEMIC AL SAFETY AND POLL Uf iO N PREVE NT IO N



### SUBJEC T: Imazethapyr. Human Health Assessme nt Scopin g Document in Support of Re gis tra t ion Review.

PC Code: 128922 , 12892 3 D ecis i o n No.: 483346 Petition N o.: N / A DP**~arcode:** 04 1 5244 Registration No.: N / A Regulatory Action: Registration Re view Scoping Document Case No.: 7208 Risk Assessment T ype: N / A TXRNo. : N / A 

# - CAS No.:**81335-7 ~**  10191 7-66- 2 40 CFR : 

### § 180.447 MRID No.: N / A


### FROM: Kelly M

. Lowe,_Env ironm entm

## Scie**tist_~~ ~**  Ch es t e r E

. Rodnguez, Ph.D. ,**Pharm co** **t ··**  

# , William D. Wassell, Chemist • 

### ' Risk Assessme nt Branch l (RAB 1) H e al t h Effec t s Division ( HED , 7509 P )

THROUGH: Charles W. S mi th III , Branch Chi ""'--

_ George F. Kramer, Ph.D. , Senior**Che mi** **~~~~2!~._,~:...--­** 

### RAB 1/HED ( 7509P)

TO: Kath e rin e St. C lair , Chemical Review Manager Pe sticide R e
- Ev aluation Division (P RD) (7508P)

Attached is HED ' s seep in g document for imazet hap yr to s upport Re gis tr atio n R ev i ew.

Pa ge 1 of 18____ Imaze!hapyr**Registrati? ~~eview**  Human Health**Ass ~~sment** **Scopin ~**  Document



### Executive Summary



### HED has prepared a seeping document to support Registration Review of imazethapyr. Imazethapyr [ ( ± 

### )-2-[ 4 ,5-d ihydro-4-methyl-4

- ( 1-methylethyl)

- 5-oxo-1 H-imidazol

- 2-yl]-5-ethyl3-pyridinecarboxylic acid] is a member of the imidazolinone class of chemicals that kills weeds by inhibiting the enzyme acetohydroxyacid synthase (AHAS). This enzyme is involved in the sy nthesis of three branched-chain aliphatic amino acids. The inhibition causes a disruption in protein synthesis that leads to an interference in D NA synthesis and cell growth. lmazethapyr, as its acid or ammonium salt, is registered for use on legume vegetables (Group 6), nongrass animal feeds (Group 18), soybean, peanut, rice, and field corn. In additio n , there is a tolerance for imazethapyr on imported canola. It 

### is also registered for use on turf, including highway rights of way , athletic fields, parks , residential lawns, sod farms , golf courses, and areas around schools/universities, libraries, hospitals , and commercial/industrial areas. In addition , there is a Special Local Needs (SLN) Registration for imazethapyr (SD 12000 l; provides additional environmental precautions and soil type restrictions) and one SLN for imazethapyr, ammonium salt (AR130002; for use on edamame). The most recent human health risk assessment was performed in 2005 and was fo r an increased tolerance on rice and crayfish (Memo, H. Johnson 

### et al

. , 11- N OV-2005 ; D321723). The re are currently no pending PRIA actions for imazethapyr.

HED has evaluated the status of the human health assessments for imaz e thapyr to determine whether sufficient data are available and whether any updates are needed to support Registration Review. HED has considered all available data and human health risk assessments for imazethapyr with r espect to its toxicity, exposure , and usage databas es, and the most updated Agency science policy and risk assessment methodologies to support Registration Re v ie w.
The toxicity database is adequate for hazard characterization and Food Quality Protec t ion Act (FQPA) Safety Factor (SF) evaluation. Imazeth apyr exhibits low toxicity in mammalian systems

. In previous risk assessments, toxicity points of departure were based on NOAELs from
s tudies where no effects were observed at th e limit dose or effects were observed at excessively high dose levels**(~1** 

### 000 mg/kg/day) not relevant for human health ri sk assessment. Thru Registration Review , it has been determined that these points of departure are no longer appropria te and no toxicological points of departure will be selected for imazethapyr for Regi stration R eview and future actions, and an add itional safety factor to prote ct children is not needed. As a result , a quantitative risk assessment is not required for imazethapyr for Registration Review to support the currently registered uses.
The residue chemistry and dietary-exposure databases for imazethapyr are adequate to support current registration requirements. The most rec e nt dietary-exposure assessment was performed for the November 2005 human health risk assessment and no risks of concern were identified. Since it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazethapyr , a quantitative dietary exposure assessment is not needed for Registration Re view for HED to conclude with reasonable certainty that dietary exposures to imazethapyr do not pose a sign ificant human health risk.

There is sufficient information available to assess occupational and residential exposure and risk from the registered uses. The most recent occupational and residential exposure assessment was
Page2 of 18Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 3 of 18 

### performed for the November 2005 human health risk assessment and no risk estimates of concern were identified

. Residential exposure scenarios have not previously been assessed. However , s ince it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazethapyr, quantitative occupational and residential exposure assessment s are not needed for Registration Review for HED to conclude with reaso nable certainty that non
dietary exposures to imazethapyr do not pose a significant human health risk. Based on the low frequency and generally low severity of incident cases reported for imazethapyr in both IDS and SENSOR

- Pesticides, there does not appea r to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a concern is triggered additional analysis will be conducted during Registration Review

. I t was noted that i n one Agricultural Health Study (AHS) study, authors observed an elevated risk of bladder and colon cancers in relation to imazethapyr use ; however, EPA notes that the structure of imazethapyr is unlike the classic structures of the carcinogenic aromatic amines and that the toxicological studies submitted to EPA for registration of imazethapyr do not show any evidence of carcinogenicity. T he Agency will continue to monitor the literature for further investigations relating to potential elevated risk of bladder and colon cancers in relation to imazethapyr use

. There are no data deficiencies for imazethapyr. Since i t has been determined that no toxicological points of departure will be selected for imazethapyr for Registr ation Review and future actions, the Agency does not anticipate the need for conducting any quantitative exposure or risk assessments during Registration Review

. 1 .0 Introduction Imazethapyr is a member of the imidazolinone class of chemicals that kills weeds by inhibiting the enzyme A HAS. This enzyme is involved in the synthesis of three branched

- chain aliphatic amino acids. The inhibition causes a disruption in protein synthesis that leads to an interference in DNA synthesis and cell growth. Imazethapyr, as its acid or ammonium sal t, is registered for use on legume vegetables (Group 6), nongrass animal feeds (Group 18), soybean, peanut, rice, and field corn. There is a tolerance for imazethapyr on imported canola. It is registered for use on turf, including highway rights of way, athletic fields, parks, residential lawns, sod farms, golf courses, and areas around schools/universities, libraries, hospitals, and commercial/industrial areas. In addition, there is a SLN Registration for imazethapyr (SD120001; provides additional envir onmental precautions and soil type restrictions) and one SLN for imazethapyr, ammonium salt (AR130002; for use on edamame). The most recent human health risk assessment was performed in 2005 and was for an increased tolerance on rice and crayfish ( Memo, H . Johnson et al. , 11

- NOV

- 2005; D321723 ). There are currently no pending PRIA actions for imazethapyr. The structure, chemical names, and other identifiers as well as the physical/chemical properties of imazethapyr can be found in Attachment 1

. 2 .0 Haza rd Characterization/Assessment The pesticidal mode of action of imazethapyr involves inhibition of the enzyme AHAS which is a key plant enzyme in the biosynthesis of the amino acids leucine, isoleucine, and valine. Mammals seem to lack this biosynthetic p athway and must obtain these amino acids from their diet. The low toxicity exhibited by imazethapyr is consistent with the proposed pesticidal mode of action and the lack thereof in mammalian systems.Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 4 of 18 

### Toxicological Studies Available for Analysis In the November 2005 risk assessment for imazethapyr , no additional toxicity data w ere deemed required because of the low toxicity exhibited by imazethapyr and structurally similar compounds (imazamox, imazapic, and imazapyr). The Hazard and Science Policy Counci l (HASPOC) met ( TXR# 0056841 , 12/ 17/13 ) to evaluate the need for inhalation, immunotoxicity, and neurotoxicity (acute and subchronic) studies

. The HASPOC concluded that these studies are not required at this time

. Therefore, the current toxicity database is adequate for hazard characterization, toxicity endpoint selection, and FQPA SF evaluation. Absorption, Distribution, Metabolism, and Excretion Following oral administration in rats, radiolabeled imazethapyr was extensively absorbed as reflected by the high percentage of the radioactivity recovered in urine (89

- 95% in the urine and 6

- 11% in the feces)

. Metabolism of the parent chemical was minimal as the major residue excreted in both urine and feces was the parent chemical

. There was no evidence of bi oaccumulation , as over 95% of the oral dose was excreted in the first 31 hours following administration. Toxicological Effects Imazethapyr exhibited very low toxicity in mammalian systems

. In subchronic and chronic toxicity studies in rats and dogs, there were no toxic effects identified [ the n o o bserved a dverse
e ffect l evel (NOAEL) was set in these studies at the highest dose tested ]

. There is no evidence of increased prenatal susceptibility following in utero exposures to rats and rabbits

. In both studies, there were no developmental effects reported at any dose , and maternal effects (increased incidence of clinical signs of toxicity, ulcerations in the stomach and gall bladder, increased abortions and maternal deaths) were reported only at the hig hest doses tested (rabbits: 1 , 000 mg/kg/day , rats: 1,125 mg/kg/day )

. Similarly, in a rat two

- generation reproductive toxicity study, there were no parental or offspring effects reported at any dose. Although there are no neurotoxicity studies available f or imazethapyr, there is no indication of neurotoxicity in any of the available studies , and neurotoxicity studies for structurally similar compounds (imazamox, imazapic, and imazapyr) do not indicate a concern for neurotoxicity. In a rabbit dermal toxici ty study, there were no effects (local or systemic) up to the highest dose tested. There is no evidence that imazethapyr is genotoxic or carcinogenic based on the results of adequate studies in mice and rats. In previous risk assessments, toxicity points of departure were based on NOAELs set either at the limit dose or on effects seen at excessively high dose levels (  1000 mg /kg/day) not relevant for human health risk assessment. Thr ough Registration Review, i t has been determined that these points of dep arture are no longer appropriate and no toxicological points of departure will be selected for imazethapyr for Registration Review and future actions, and an additional safety factor to protect children is not needed. As a result, a quantitative risk asse ssment is not required for imazethapyr for Registration Review to support the currently registered uses.

Conclusions : The toxicology database is adequate to support existing registrations and registration review (Attachment 2). No additional toxicological studies are currently required. N o toxicological points of departure were selected for imazethapyr for Registration Review and an additional safety fac tor to protect children is not needed. As a result, a quantitative risk assessment is not required for imazethapyr for Registration Review to support the currently registered uses.Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 5 of 18 

### 3 .0 Residue Chemistry The nature of the imazethapyr residue in plants, poultry , ruminants , and crayfish is adequately understood based on adequate metabolism studies with soybean, green bean, lettuce, imidazolinone

- tolerant corn, peanut, laying hens, and lactating goats . Based upon these data, the HED Metabolism Assessment R eview Committee (MARC) concluded that the residue of concern in/on canola, soybean, and legume vegetables (Group 6) is imazethapyr. The MARC further concluded that the residue of concern in nongrass animal feed (Group 18), peanut, and rice are imazethapyr and its metabolites , CL 288511 and CL 182704, both free and conjugated. Additionally , the residues of concern in ruminant tissues, corn, crayfish, endive, and lettuce are imazethapyr and its metabolite CL 288511 (free and conjugated). Adequate confined field rotational crop trial data are available , and support the label

- specified plantba ck intervals ( PBIs ) for crops without uses on the imazethapyr label. In previous imazethapyr risk assessments, the following data were conditionally required: a clover residue data (three field trials), a ruminant feeding study, and a crayfish residue study. In 2004, a study was submitted that would fulfill the crayfish residue study requirement (Johnston, R., 2004, Field Accumulation Study of BAS 685 H (AC 263499 Imazethapyr) and Its Metabolite (CL 288511) in Crayfish, Procambarus clarkii: Final Study Report ). The other two data requirements are no longer considered necessary since a qualitative assessment is sufficient based on the low toxicity of imazethapyr

. Conclusions: Adequate residue data are available to support the registered uses of im azethapyr.

4.0 Dietary Exposure and Risk Assessment The most recent dietary

- exposure assessment was performed for the 2005 human health risk assessment ( Memo, H. Johnson et al. , 11

- NOV

- 2005; D321723 ) and no risks of concern were identified

. Since it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazethapyr, a quantitative dietary exposure assessment is not needed for Registration Review for HED to conclude with reasonable certainty that dietary e xposures to imazethapyr do not pose a significant human health risk.

Conclusions : The dietary

- exposure database is adequate to support current registration requirements. Since it has been determined that a qualitative assessment is sufficient based on t he low toxicity of imazethapyr, a quantitative dietary exposure assessment is not needed for Registration Review for HED to conclude with reasonable certainty that dietary exposures to imazethapyr do not pose a significant human health risk.

5 .0 Resident ial Exposure /Risk Assessment Imazethapyr is currently registered for use on turf, including areas around schools/universities, athletic fields, parks, residential lawns, and golf courses. Residential exposures from these uses have not previously been quantitatively assessed

. However, since it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazethapyr, a quantitative residential exposure assessment is not needed for Registration Review for HED to conclude with reasonable certainty that residential non
- dietary exposures to imazethapyr do not pose a significant human health risk.Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 6 of 18 

### Spray Drift Residential exposures resulting from off

- site transport (e.g., spray drift or volatilization) may occur as a result of applications of imazethapyr ; however, due to the low toxicity of imazethapyr, quantitative spray drift and/or bystander assessments are n ot necessary for Registration Review

. Conclusions : The residential

- exposure database is adequate to support current registration requirements. Since it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazet hapyr, a quantitative res i dential exposure assessment is not needed for Registration Review for HED to conclude with reasonable certainty that residential non
- dietary exposures to imazethapyr do not pose a significant human health risk.

6 .0 Aggregate Exposure/ Risk Assessment The most recent aggregate

- risk assessment was performed in conjunction with the November 2005 human health r isk assessment ( Memo, H. Johnson et al. , 11

- NOV

- 2005; D321723 )

. Since no residential uses were assessed previously and th ere was no acute dietary point of departure for imazethapyr , only chronic aggregate assessments were conducted, which took into consideration dietary food plus water e xposures. S ince it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazethapyr, a quantitative aggregate risk assessment is not needed for Registration Review for HED to conclude with reasonable certainty that aggregate exposures to imazethapyr do not pose a significant human health risk.

Conclu sions : Since it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazethapyr, a quantitative aggregate exposure assessment is not needed for Registration Review for HED to conclude with reasonable certainty that aggregate exposures to imazethapyr do not pose a significant human health risk.

7 .0 Occupational Exposure /Risk Assessment Occupational handler and post

- application exposures are expected b ased on the registered agricultural uses of imazethapyr

. Attachment 4 provides a summary of the occupational use pattern. The current registrations include some SLN registrations. The application rates range from 0.003

– 0.09 5 lb ai/A, and applications can be made either pre

- or post

- emergence. Most labels appear to restrict over

- the

- top sprays or allow them only up to an early crop stage (i.e., when few leaves are present). The most recent occupational risk assessment was performed in conjunction with the November 2005 human health r isk assessment ( Memo, H. Johnson et al. , 11

- NOV

- 2005; D321723 ) Since it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazetha pyr, a quantitative occupational exposure assessment is not needed for Registration Review for HED to conclude with reasonable certainty that occupational non

- dietary exposures to imazethapyr do not pose a significant human health risk.

In accordance with the updated Part 158 data requirements (2007), one or more dislodgeable foliar residue (DFR) studies are required when a pesticide has occupational uses that could result in post

- application dermal exposure. However, s ince no quantitative dermal exposure assessment is necessary for imazethapyr, a DFR study is not required at this time. Imazethapyr has low acute toxicity via the oral, dermal and inhalation routes (Toxicity Categories III and IV). It is not an eye (Toxicity Category III) or skin irritan t (Toxicity CategoryImazethapyr Registration Review Human Health Assessment Scoping Document

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Page 7 of 18 

### IV). Imazethapyr was no t shown to be a skin sensitizer

. Under 40 CFR 156.208 (c) (2) (iii),
a ctive i ngredient s classified as Acute Toxicity III or IV for acute dermal, eye i rritation and primary skin irrit ation are assigned a 12

- hour REI. Therefore, the [156 subpart K] Worker Protection Statement (WPS) interim REI of 12 hours is adequate to protect agricultural workers from post

- application exposures to imazethapyr

. The restricted entry intervals on the re gistered labels for imazethapyr range from 4 to 24 hours

. PRD should ensure that the appropriate REI is listed on the product labels. Many of the products contain multiple active ingredients, which may warrant a longer REI. In addition, while the WPS

- re commended REI for imazethapyr based on its acute toxicity categories is 12 hours, REIs may be further reduced if certain criteria are met for both the technical material and the different end

- use products in accordance with the Pesticide Registration (PR) Notice 95

- 3 [Reduction of Worker Protection Standard (WPS) Interim Restricted Entry Intervals (REIs) for Certain Low Risk Pesticides] 1



### . Imazethapyr meets one of the criteria for a reduction to a 4

- hr REI b ased only on its acute toxicity categories, howeve r, during Registration Review, the additional criteria listed in PR Notice 95

- 3 will be checked to ensure they are met for both the active ingredient and the end

- use product for those products listing a 4

- hr REI

. Conclusions : The occupational exposure database is adequate to support the Registration Review process for imazethapyr

. Since it has been determined that a qualitative assessment is sufficient based on the low toxicity of imazethapyr, a quantitative occupational exposure assessment is not nee ded for Registration Review for HED to conclude with reasonable certainty that occupational non

- dietary exposures to imazethapyr do not pose a significant human health risk. During Registration Review, the products listing a 4

- hour REI will be checked aga inst the criteria listed in PR Notice 95

- 3 to ensure they are met for both the active ingredient and the end

use product for those products listing a 4

- hr REI

. 8 .0 Public Health and Pesticide Epidemiology Data Memo, E. Evans, S. Recore, C. Christensen, D416459, 18

- DEC

- 2013.


### T he OPP Incident Data System (IDS) and the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk

- Pesticides (SENSOR) databases were consulted for pesticide incident data on the active ingredient imazethapyr ( PC codes: 128922, 128923). The purpose of the database search wa s to identify potential patterns in the frequency and severity of the health effects attributed or p otentially attributed to imazethapyr exposure. Imazethapyr is also included in the Agricultural Health Study ( AHS ) , and review of studies within the AHS was also conducted

. For the Main IDS (which contains incidents resulting in higher severity outcomes and provides more detail with regard to case specifics ) , there were no incidents reported for the single chemical active ingredient imazethapyr in the database from January 1, 2008 to September 11, 2013 . There was one incident reported involving more than one chemical including imazethapyr. This incident was classified as moderate severity , but due to the nature of the report, i.e. , multiple chemical exposure, there is little information to glean for the imazethapyr risk assessment. In Aggregate IDS (whic h contains incidents resulting in less severe human incidents (minor, unknown, or no effects outcomes) ) , there were eight reported incidents involving imazethapyr from January 1, 2008 to September 11, 2013 . These incidents were all classified as minor seve rity. Overall, there are few incidents involving imazethapyr reported to

1 Available: http://www.epa.gov/PR_Notices/pr95

- 3.htmlImazethapyr Registration Review Human Health Assessment Scoping Document

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Page 8 of 18 

### IDS. A query of SENSOR

- Pesticides from 1998

- 2009 identifie d no single ai cases involving imazethapyr and one multiple ai case involving imazethapyr. This case was low in severity. The low frequency and low severity of acute poisoning cases (also referred to as human incident data) reported for imazethapyr in both the IDS and SENSOR

- Pesticides does not trigger an EPA concern at this time. The Agency will continue to monitor the inc ident information , and if the magnitude and frequency of reported acute poisoning events increases, additional analysis will be performed. In one Agricultural Health Study (AHS) study, authors observed an elevated risk of bladder and colon cancers in rel ation to imazethapyr use. Authors state the findings are supported by the relatedness of imazethapyr to other heterocyclic amine (HCA) compounds , which are putative risk factors for these cancers. While this study does show a potential association between bladder and colon cancer and imazethapyr use, EPA notes that the HCA structure of imazethapyr is unlike the classic structures of the carcinogenic aromatic amines and that the toxicological studies submitted to EPA for registration of imazethapyr do not s how any evidence of carcinogenicity. EPA will continue to monitor the literature for further investigations on this topic.

Conclusions : Based on the low frequency and generally low severity of incident cases reported for imazethapyr in both IDS and SENSOR

- Pesticides, there does not appear to be a concern at this time that would warrant further investigation. The Agency will continue to monitor the incident information and if a concern is triggered additional analysis will be conduct ed during Registration Review

. In addition, the Agency will continue to monitor the literature for further investigations relating to potential elevated risk of bladder and colon cancers in relation to imazethapyr use

. 9 .0 Tolerance Assessment and Inter national Harmonization

Current U.S. permanent tolerances (listed in 40 CFR 180. 447 ) are summarized in Attachment 5

. HED recommends that the following tolerance issues should be considered during Registration Review: 1) T olerances listed for imazethapyr on e ndive and lettuce should be revoked as there are no current registrations for these commodities. 2) Potential for harmonization of U.S. tolerances and Canadian MRLs for canola (or rapeseed), field corn grain, and dry lentils. 3) Potential for the establishment o f tolerances for residues of imazethapyr in/on the oilseed group (group 20) as Canadian MRLs are established for imazethapyr borage seeds, cuphea seeds, echium seeds, flaxseeds, gold of pleasure seeds, hare's ear mustard seeds, milkweed seeds, mustard seed s (oil seed type), oil radish seeds, poppy seeds, sesame seeds, sweet rocket seeds, fenugreek seeds, and sunflower seeds; however, the U.S. does not have established tolerances for imazethapyr on these commodities. 4) The tolerance expression for imazethapyr should be changed for harmonization purposes and to conform to current HED policy. Specifically, the tolerance expression for 40 CFR §180. 477 ( all subsections ) should be as follows: Tolerances are established for residues of imazethapyr including its metabolites and degradates, applied as its acid or ammonium salt, in or on the commodities listed in the following table. Compliance with the tolerance levels specified are to be determined by measuring only imazethapyr [ (±)

- 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1H

-Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 9 of 18 

### imidazol

- 2

- yl]

- 5

- ethyl

- 3

-

pyridine carboxylic acid], in or on the following food commodities:
10.0 Environmental Justice Potential areas of environmental justice concerns, to the extent possible, were considered in the most recent imazethapyr human health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions to Address Environmental Justice in Mino rity Populations and Low

Income Populations,” ( http://www.epa.gov/compliance/environmentaljustice/resources/policy/exec_order_12898.pdf ). The OPP typica lly considers the highest potential exposures from the legal use of a pesticide when conducting human health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets wi thin the U.S., and people who may be exposed when harvesting crops. Should these highest exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure that the risk estimates are based on the best available information.
11.0 Cumulative Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for imazethapyr and any other substances; and imazethapyr doe s not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that imazethapyr does not have a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

1 2 .0 Risk Assessment Updates and Data Deficiencies There are no data deficiencies for imazethapyr. Since i t has been determined that no toxicological points of departure will be selected for imazethapyr for Registration Review and future actions , the Agency does not anticipate the need for conducting any quantitative exposure or risk assessments during Registration Review

. 1 3 .0 References
Memoranda Relevant to Registration Review. Author Barcode Date Title S. Koepke None 02/06/91 PP# 0F3870 Imazethapyr (Pursuit®) In or On Corn Forage, Silage, Grain and Fodder. Request for Petition Method Validation Trials of Analytical Method SOP M1981.

S. Koepke D170056 02/06/91 Pursuit (Imazethapyr). Review The Submitted Comments of the Meeting of October 7, 1991 with Representatives of American Cyanamid Company Concerning the Data Requirements for Pursuit on Corn and Peanuts. S. Koepke None 04/01/91 PP# 0F3870 Imazethapyr (Pursuit®) in or on Corn Forage, Silage, Grain and Fodder. Evaluation of Analytical Methods and Residue Data.Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 10 of 18 Memoranda Relevant to Registration Review. Author Barcode Date Title
S. Koepke None 05/15/91 PP# 0F3870 Imazethapyr (Pursuit®) in or on Corn Forage, Silage, Grain and Fodder Results of Petition Method Validation of the hydroxylated metabolite (Cl 288,511). S. Koepke None 08/15/91 PP# 0F3870 Imazethapyr (Pursuit®) in or on Corn Forage, Silage, Grain and Fodder. Review of Petitioner's June 20, 1991 Response to Deficiencies. S. Koepke None 09/25/91 Conference of September 25, 1991 with Toxicology Branch I. Discussion of Toxicological Significance of Pursuit Metabolites. S. Koepke D172262 03/03/92 PP# 0F3870 Imazethapyr (Pursuit®) i n or on Corn Forage, Silage, Grain and Fodder. Review of Petitioner's Responses to Deficiencies dated 11/19/91. G. Herndon D189669 4/28/93 ID#: 93FL0007; Section 18 Exemption For Use of Imazethapyr on Lettuce and Endive. F. Griffith, Jr. D167657 05/25/93 PP# 1F4013

- Imazethapyr (Pursuit®) in Alfalfa Hay. Forage, and Seed. Review of Analytical Method and Residue Data.

F. Griffith, Jr. D175956 08/18/93 PP# 0F3870

- Imazethapyr (Pursuit®) on Corn Grain, Forage, Fodder, and Silage. Review of the P etitioner's Memorandum of Understanding of the April 29, 1992, Meeting, Update on Proposed Analytical Method Revisions, Draft for Revised Residue Analytical Method, Additional Independent Laboratory Validation Data, and Revised Tolerance proposal.

F. Griffith, Jr. D194534 08/27/93 PP# 1F4013

- Imazethapyr (Pursuit®) in Alfalfa Hay, Forage, and Seed. Request for Additional Analytical Reference Standard, Data Detailing

How the Standard Was Characterized, and a Comparison Between Standards. F. Griffith, Jr. D188634 10/13/93 PP# 1F4013

- Imazethapyr (Pursuit®) in Alfalfa Hay, Forage, and Seed. Review of the January 28, 1993, Amendment. F. Griffith, Jr. D196896 11/30/93 ID#: 94CA94006 Section 18 Exemption For Use Of Imazethapyr (Pursuit®) On Alfalfa. F. Griffith, Jr. D197216 02/02/94 PP# 1F4013

- Imazethapyr (Pursuit®) in Alfalfa Forage, Hay and Seed. Tolerance Method Validation Requests. F. Griffith, Jr. D196948 02/02/94 PP# 1F4013

- Imazethapyr (Pursuit®) in Alfalfa Forage, Hay, and Seed. Review of New Residue Analytical Method.

R. Cook D205581 07/21/94 94FL0010. Imazethapyr [Pursuit® Herbicide, EPA Reg. No. 241

- 310] as its ammonium salt in or on lettuce and endive (escarole) in Florida only. Submission dated 7/07/94.

R. Cook D197216 11/08/94 PP# 1F04013. Imazethapyr [Pursuit® Herbicide] in or on Alfalfa Forage, Hay and Seed. ACL Tolerance Method Validation Report. March 18, 1994 and Oct. 17, 1994. R. Cook D201538 11/10/94 PP# 1F04013. Imazethapyr [Pursuit® Herbicide] in or on alfalfa fo rage, hay and seed. Review of petitioners response to previous reviews.

R. Cook D194850 12/13/94 PP# 3E04241. Imazethapyr [Pursuit® Herbicide] as its ammonium salt in or on lettuce and endive (escarole) in Florida only. Evaluation of Analytical Metho d and Residue Data. Submission dated 7/06/93.

R. Cook D210387 01/17/95 PP# 1F04013. Imazethapyr [Pursuit® Herbicide] in or on alfalfa forage, hay and seed. Review of petitioners response to previous reviews. DP Barcode D210387. J. Stokes D230401 01/07/97 PP#0F3870. Imazethapyr in/on RAC Corn. Revised Section F dated September 23, 1996. T. Bloem D272022 01/23/2001 ID# 01LA0002: Section 18 for Application of Imazethapyr to Rice. Chronic Dietary Exposure Analysis

. P. V. Shah et al

. D271177 02/06/2001 ID# 01LA0002

- Section 18 for Application of Imazethapyr to Rice in Louisiana.

T. Bloem D273086 03/13/2001 PP# 0F06186

- Imazethapyr in/on Rice. Petition Method Validation (PMV) Request.
T. Bloem D273086 03/13/2001 PP# 0F06186

- Imazethapyr in/on Rice. Request for a Metabolism Study Performed on Imidazolinone

- Resistant Rice.

T. Bloem et al

. D280365 01/18/2002 ID#s

- 6F04746 (non

- grass animal feed),1E06286 (import tolerance; imidazolinone

- tolerant canola), and 0F06186 (crayfish and imidazolinone

tolerant rice)

- Imazethapyr in/on Nongrass Feed, Imidazolinone

- Tolerant Canola (Import), Imidazolinone

- Tolerant Rice, and Crayfish. Metabolism Assessment Review Committee (MARC) Briefing Document. T. Bloem D279832 02/07/2002 ID# 1E06286

- Import Tolerance for Imidazolinone

- Tolerant Canola.Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 11 of 18 Memoranda Relevant to Registration Review. Author Barcode Date Title Petition Method Validation (PMV) Request.

T. Bloem et al

. D280609 03/07/2002 ID#s

- 6F04746 (non

- grass animal feed), 1E06286 (import tolerance; imidazolinone

- tolerant canola), and 0F06186 (crayfish and imidazolinone

tolerant rice)

- Health Effects Division (HED) Metabolism Assessment Review Committee (MARC) Decision Document.

T. Bloem D281431 03/14/2002 Imazethapyr Chronic Dietary Exposure Assessment for the Proposed Section 3 Registrations on Imidazolinone

- Tolerant Rice (ID # 0F06186), Imidazolinone

- Tolerant Canola (1E06286), and the non

- Grass Animal Feed Crop Group (6F04746).

T. Bloem et al

. D282248 04/11/2002 ID#s

- 6F04746 (non

- grass animal feed), 1E06286 (import tolerance; imidazolinone

- tolerant canola), and 0F06186 (crayfish and imidazolinone

tolerant rice)

- Amendment to Health Effects Division (HED) Metabolism Assessm ent Review Committee (MARC) Decision Document

- D280609. T. Bloem D282112 04/18/2002 PP# 0F06186

- Imazethapyr in/on Rice. Crayfish and Liver Petition Method Validation (PMV) Request.

T. Bloem D278993 04/22/2002 ID#s

- 6F04746 (nongrass animal feed crop group), 1E06286 (import tolerance; imidazolinone

- tolerant canola), and 0F06186 (crayfish and imidazolinone

- tolerant rice)

- Imazethapyr in/on Nongrass Feed, Imidazolinone

- Tolerant Canola (Import), Imidazolinone

- Tol erant Rice, and Crayfish. Evaluation of Residue Data and Analytical Methods.

T. Bloem et al

. D232428 04/23/2002 ID#s

- 6F04746 (nongrass animal feed crop group), 1E06286 (import tolerance; imidazolinone

- tolerant canola), and 0F06186 (crayfish and imida zolinone

- tolerant rice)

- Health Effects Division (HED) Risk Assessment for Imazethapyr.

T. Bloem D283383 06/25/2002 ID#s

- 6F04746 (nongrass animal feed crop group), 1E06286 (import tolerance; imidazolinone

- tolerant canola), and 0F06186 (crayfish and imidazolinone

- tolerant rice)

- Imazethapyr in/on Nongrass Feed, Imidazolinone

- Tolerant Canola (Import), Imidazolinone

- Tolerant Rice, and Crayfish. Petitioners Response (24

- May

- 2002) to Deficiencies Identified in HED’s Residue Chemistry Review (D278993, T. Bloem, 22

- Apr

- 2002).

T. Bloem D286253 11/21/2002 Imazethapyr (PC Code 128923). Section 3 Registration for Application of Imazethapyr (ammonium salt) to Imidazolinone

- Tolerant Rice (ID # 000241

- 00412). Petitioners Response (17

- Oct

- 2002) to Deficiencies Identified in the D278933 Residue Chemistry Memorandum.

T. Bloem D288669 03/20/2003 Imazethapyr (PC Code 128923). Section 3 Registration for Application of Imazethapyr (ammonium salt) to Imidazolinone

- Tolerant Rice (ID#

- 0F06186). Review of a Crayfi sh Feeding Study Protocol. H. Johnson D321721 11/03/2005 Imazethapyr: Chronic Dietary Exposure Assessment for the Section 3 Registration Tolerance Increase on Rice. H. Johnson D321723 11/07/2005 Imazethapyr : Human Health Risk Assessment for Tolerance Increase on Rice and Crayfish

. E. Evans et al. D416459 12/ 19 / 13 Imazethapyr : Tier I Review of Human Incidents


### Attachments:

Attachment 1: Imazethapyr Identity and Physicochemical Properties
. Attachment 2 : Imazethapyr Acute, Subchronic, and Chronic Toxicity Profile
. Attachment 3 : Summary of Occupational and Residential Registered Uses
. Attachment 4 : Imazethapyr International Residue Limit Status Sheet.

cc: K. Lowe (RAB1), W. Wassell (RAB1), C. Rodr iguez (RAB1) RDI: RAB1 ( 12/11/13 ), D. Vogel ( 12/30/13 ) K.Lowe :S109 4 7:PY

- S:(703)3 47

- 8989 :7509P:RAB1Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 12 of 18 

### Attachment 1: Imazethapyr Identity and Physicochemical Properties
. Imazethapyr Nomenclature. Imazethapyr Chemical structure

Common name Imazethapyr IUPAC name (±)

- 5

- ethyl

- 2

- (4

- isopropyl

- 4

- methyl

- 5

- oxo
- 2

- imidazolin

- 2

- yl) nitotinic acid CAS name (±)

- 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1 H

- imidazol

- 2

- yl]

- 5

- ethyl

3

- pyridinecarboxylic acid CAS registry number 81335

- 77

- 5 Imazethapyr salt Chemical structure

Common name Imazethapyr ammonium IUPAC name ammonium 5

- ethyl

- 2

- [( RS )

- 4

- isopropyl

- 4

- methyl

- 5

- oxo
- 2

- imidazolin

- 2

- yl]nicotinate CAS name ammonium 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1 H

- imidazol

- 2

- yl]

- 5

- ethyl

- 3

- pyridinecarboxylate CAS registry number 101917

- 66

- 2
Physicochemical Properties of the Technical Grade Test Compound: Imazethapyr Parameter Value Reference Melting range 169

– 173 o C D321723, 11/7/05, H. Johnson pH Not available Density 0.459 g/ml D321723, 11/7/05, H. Johnson Water solubility 0.14 g/100 ml (distilled) D321723, 11/7/05, H. Johnson Solvent solubility Not available Vapor pressure 1 x 10 - 7 mm Hg at 60 o C D321723, 11/7/05, H. Johnson Dissociation constant, pK a Not available Octanol/water partition coefficient 11 at pH 5; 31 at pH 7; 16 at pH 9 D321723, 11/7/05, H. Johnson
UV/visible absorption spectrum Not availableImazethapyr Registration Review Human Health Assessment Scoping Document

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Page 13 of 18 

### Attachment 2 : Imazethapyr Acute, Subchronic, and Chronic Toxicity Profile
Acute Toxicity Profile

- Imazethapyr Technical
. Guideline No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 00159375 LD 50  5,000 mg/kg (male and female rats) IV

870.1200 Acute Dermal 00159375 LD 50  2,000 mg/kg (male and female rabbits) III

870.1300 Acute Inhalation 00159378 LD 50  3.27 mg/L (male and female rats) III 870.2400 Primary Eye Irritation 00159375 Not an irritant III 870.2500 Primary Skin Irritation 00159375 Not an irritant IV 870.2600 Dermal Sensitization 00159379 Not a skin sensitizer N/A
Subchronic, Chronic, or Other Toxicity Profile of Imazethapyr. Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.3100 90

- Day oral toxicity rodents

- rat 00159381 (1986)

Acceptable/guideline 0, 1,000, 5,000, or 10,000 ppm 0, 50, 250, or 500 mg/kg/day NOAEL = 500 mg/kg/day (HDT). LOAEL = not observed.

870.3150 90

- Day oral toxicity nonrodents

- dog 00159382 (1985)

Acceptable/guideline 0, 1,000, 5,000 or 10,000 ppm 0, 25, 125 or 250 mg/kg/day NOAEL = 250 mg/kg/day (HDT). LOAEL = not observed.

870.3200 21

- Day dermal toxicity

- rabbit 00159383 (1985)

Acceptable/guideline 0, 50, 200, or 1000 mg/kg/day 0, 54.8, 219.3, or 1096.5 mg/kg/day (adjusted for purity) NOAEL = 1096 mg/kg/day (HDT). LOAEL = not observed.

870.3700a Prenatal developmental in rodents

- rat 40429417 (1985)

Acceptable/guideline 0, 125, 375, or 1125 mg/kg/day Maternal : NOAEL= 375 mg/kg/day. LOAEL 1 = 1,125 mg/kg/day based on increased incidences of clinical signs during the gestation. Developmen tal : NOAEL = 1,125 mg/kg/day. LOAEL = not observed.

870.3700b Prenatal developmental in nonrodents

- rabbit 00159384 (1986)

Acceptable/guideline 0, 100, 300, or 1,000 mg/kg/day Maternal : NOAEL = 300 mg/kg/day. LOAEL 1 = 1,000 mg/kg/day based on an increased incidence of clinical signs during gestation, ulcerations in the mucosal layer of the stomach and gall bladder, increased abortions, and maternal deaths. Developmental : NOAEL = 1,000 mg/kg/day (HDT). LOAEL = not o bserved.

870.3800 Reproduction and fertility effects

- rat 40429418 (1987)

Acceptable/guideline 0, 1,000, 5,000 or 10,000 ppm 0, 50, 250 or 500 mg/kg/day Parental/Systemic NOAEL = 500 mg/kg/day (HDT). LOAEL = not observed. Reproductive NOAEL = 500 mg/kg/d ay (HDT). LOAEL = not observed. Offspring NOAEL = 500 mg/kg/day (HDT). LOAEL = not observed.

870.4100b Chronic toxicity

- dog 40429416 (1987)

Acceptable/guideline 0, 1,000, 5,000 or 10,000 ppm 0, 25, 125, or 250 mg/kg/day NOAEL = 250 mg/kg/day (HDT). LOAEL = not observed.

870.4300 Chronic/ Carcinogenicity

- rat 40429414 (1987)

Acceptable/guideline 0, 1,000, 5,000, or 10,000 ppm 0, 50, 250, or 500 mg/kg/day NOAEL = 500 mg/kg/day (HDT). LOAEL = not observed. No evidence of carcinogenicity.Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 14 of 18 Subchronic, Chronic, or Other Toxicity Profile of Imazethapyr. Guideline No./ Study Type MRID No. (year)/

Classification /Doses Results

870.4300 Carcinogenicity

mouse 40429415 (1987)

Acceptable/guideline 0, 1,000, 5,000, or 10,000 ppm 0, 150, 750, or 1500 mg/kg/day NOAEL = 750 mg/kg/day. No evidence of carcinogenicity at doses tested.

870.5100 Gene Mutation 00159719 (1986)

Acceptable/guideline 0, 50, 158, 500, 1000, 1581, 3162 or 5,000 μg/plate Non

- mutagenic when tested up to 5000 ug/plate, in presence and absence of metabolic activation, in S. typhimurium strains TA98, TA100, TA1535, TA1537, and TA 1538 and E.coli strain WP2uvra.

870.5300 Gene Mutation 40429419 (1986)

Acceptable/guideline up to 3333 μg/mL (limit of solubility) and 4000 μg/mL (beyond limit of solubility) Negative for induction of forward mutation at the HPRT locus in Chinese hamster ovary cells, in the presence or absence of S9

- activation at doses up to limit of solubility (3333 μg/mL) and beyond (4000 μg/mL).

870.5375 Chromosome aberration 40438201 (1986)

Acceptable/guideline 0, 1.14, 1.71, 1.82, 2.05, and 2.28 mg/ml with and without S9 activation Did not induce structural c hromosome aberration in Chinese hamster lung (V79) cell cultures in the presence and absence of activation up to cytotoxic concentrations.

870.5450 Dominant Lethal Assay 00159720 (1985)

Unacceptable/guideline 0, 200, 1000 or 2000 mg/kg Negative for domina nt lethal effects (chromosomal damage) at doses up to 2000 mg/kg.

870.5550 Other Genotoxicity 00159721 (1985)

Acceptable/guideline 0, 0.13, 0.4, 1.3, 4.0, 13, 40, 133, 400, 1333, or 4000 μg/mL No evidence that unscheduled DNA synthesis was induced by imazethapyr, as determined by radioactive tracer procedures [nuclear silver grain counts].

870.7485 Metabolism and pharmacokinetics

– rat 40429420 and 41467703 (1987)

5.7 mg/kg single dose; 1000 mg/kg single dose and 3 daily doses of 250 mg/kg followed by a single dose of 1000 mg/kg; 1000 mg/kg/day single and repeated dose In a rat metabolism study, almost 100% of the administered radiolabeled test material was recovered in the excreta within 96 hours (89

- 95% in the urine and 6

- 11% in the feces). Greater than 95% of the oral dose was excreted in the first 31 hours. The major residue in both urine and feces was the parent compound. Approximately 2% of the oral dose was metabolized and excreted as CL 288511 (1

- hydroxy ethyl derivative of AC 263,499, parent)

. A high percentage of the administered material was excreted in the urine as the unmodified parent compound (>97%) and a very small amount as the CL 288511. In the high dose group, the unmodified parent compound was the major fecal component in both
sex es, particularly at 12 hours or less. The CL 288511 was the major metabolite. One unknown was also found in significant quantities. In the low dose group, six components were found in the feces: parent compound, the CL 288511, the unknown previously
me ntioned and several minor unknowns. 1 T he LOAELs from these studies were greater than or equal to the limit dose of 1000 mg/kg/day and, in combination with the low toxicity of other toxicity studies, are therefore considered not relevant f or human health risk assessment.Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 15 of 18 

### Attachment 3 : Summary of Occupational and Residential Registered Uses

Crop/Use Site Formulation Application method Maximum App Rate (lb ai/A) REI 

### Imazethapyr

Alfalfa Liquid ground and aerial (no chemigation) 0.094 48 hours WSP 0.095 12 hours

Clearfield and IMI corn hybrids DF ground and aerial (no chemigation) 0.063 12

- 48 hours Liquid aerial, ground, dry bulk

fertilizer (no chemigation) 0.063 24

- 48 hours

Clearfield rice DF ground and aerial (no chemigation) 0.094 12 hours

Clover DF ground and aerial (no chemigation) 0.095 12 hours Forage Legumes and Grasses (Federal Conservation Reserve Program and Agricultural Reserve Prog r am Land) DF ground and aerial (no chemigation) 0.063 12 hours

Peanuts Liquid ground and aerial (no chemigation) 0.050 12 hours DF 0.063 12 hours

Peas and Beans WSP aerial and ground (no chemigation; aerial is prohibited for red kidney beans and snap beans) 0.063 12 hours

DF ground only (no aerial or

chemigation) 0.047 12 hours
Liquid 24 hours

ground and aerial (no chemigation) 0.031 12 hours Residential, Commercial and institutional Lawns, Athletic Fields, Commercial Sod Farms, Golf Course Fairways and Roughs, Railroad Rights

- of

- Way, Highway, Roadside, Pipeline and Utility Rights

- of

- Way, Industrial Areas, Fence Rows and Other Non

- crop Sites L iquid Aerial, Groundboom, Handheld (no chemigation) 0.075 NS

Soybeans DF and WSP ground and aerial (no chemigation) 0.063 12 hours Liquid aerial, ground, dry bulk

fertilizer (no chemigation) 0.064 12

- 48 hours 

### Imazethapyr Salt
Alfalfa Liquid ground and aerial (no chemigation) 0.094 4 hours

Clearfield rice Liquid ground and aerial (no chemigation) 0.094 4 hours Clearfield corn hybrids Liquid ground and aerial (no chemigation) 0.063 4 hours

Clover Liquid ground and aerial (no chemigation) 0.094 4 hours

Edamame Liquid ground and aerial (no chemigation) 0.063 4 hours Forage legumes and grasses Liquid ground and aerial (no chemigation) 0.063 4 hours Highway rights of way, land around schools/universities, libraries, hospitals, commercial/industrial areas, Liquid Aerial, ground (no chemigation) 0.003 NAImazethapyr Registration Review Human Health Assessment Scoping Document

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Page 16 of 18 Crop/Use Site Formulation Application method Maximum App Rate (lb ai/A) REI athletic fields, parks, golf course

roughs Legume (trefoil) Liquid ground and aerial (no chemigati on) 0.063 4 hours

Peanuts Liquid ground and aerial (no chemigation) 0.063 4 hours Peas and Beans (some restrictions by

specific variety) Liquid ground and aerial (no chemigation; no aerial for kidney or snap beans) 0.063 4 hours

Soybeans Liquid ground and aerial (no chemigation) 0.063 4

- 24 hoursImazethapyr Registration Review Human Health Assessment Scoping Document

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Page 17 of 18 

### Attachment 4 : Imazethapyr International Residue Limit Status Sheet

. International Residue Limits (128922/128923; 10/23/2013)
Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 40 CFR 180.447 (a) General. (1) imazethapyr, 2

- [4,5

- dihydro

4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1H

imidazol

- 2

- yl]

- 5

- ethyl

- 3

- pyridine carboxylic acid, applied as its acid or ammonium salt (±)

- 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo

- 1 H

- imidazol

- 2

- yl]

- 5

- ethyl

- 3

- pyridineca rboxylic acid, expressed as ammonium salt None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Canola, seed 1 0.10 0.05 rapeseeds (canola) Soybean 0.1 0.1 dry soybeans Vegetable, legume, group 6 0.1 0.1 Dry (Dutch brown beans, adzuki beans, black beans, cranberry beans, kidney beans, lima beans, navy beans, pink beans, pinto beans, red beans, soybeans, tepary beans, white beans, yelloweyed beans), peas; Edible

- podded (runner beans, snap beans, wax beans); s ucculent shelled lima beans 0.05 dry lentils
(2) Sum of the residues of the herbicide imazethapyr, 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1H

- imidazol

- 2

- yl]

- 5

- ethyl

- 3

- pyridine carboxylic acid; its metabolite CL 288511, 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1H

- imidazol

2

- yl]

- 5

- (1

- hy droxyethyl)

- 3

- pyridine carboxylic acid; and its metabolite CL 182704, 5

- [1

- (beta

- D

glucopyranosyloxy)ethyl]

- 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1H

- imidazol

2

- yl]

- 3

- pyridinecarboxylic acid, applied as its acid or ammonium salt Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Alfalfa, seed 0.15 Alfalfa, seed screenings 0.15 Animal feed, nongrass, group 18, forage 3.0 Animal feed, nongrass, group 18, hay 5.5 Peanut 0.1 Rice, bran 1.2 Rice, grain 0.3 Rice, straw 0.4Imazethapyr Registration Review Human Health Assessment Scoping Document

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Page 18 of 18 Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex (3) Sum of residues of the herbicide imazethapyr, 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1H

- imidazol

- 2

- yl]

- 5

- ethyl

- 3

- pyridine carboxylic acid, and its metabolite CL 288511, 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1H

imidazol

- 2

- yl]

- 5

- (1

- h ydroxyethyl)

- 3

- pyridine carboxylic acid, applied as its acid or ammonium salt Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Cattle, meat byproducts 0.10 Corn, field, forage 0.1 Corn, field, grain 0.1 0.05 Corn, field, stover 0.1 Crayfish 0.15 Goat, meat byproducts 0.10 Hog, meat byproducts 0.10 Horse, meat byproducts 0.10 Sheep, meat byproducts 0.10 MRLs with NO US Equivalent Borage seeds, cuphea seeds, echium seeds, flaxseeds, gold of pleasure seeds, hare's ear mustard seeds, milkweed seeds, mustard seeds (oil seed type) , oil radish seeds, poppy seeds, sesame seeds, sweet rocket seeds 0.05

Fenugreek seeds 0.05 Sunflower seeds 0.1 Completed: M. Negussie; 10/29/13 1 There are no U.S. registrations for canola as of March 21, 2003. 2 Mexico adopts U.S. tolerances and/or Codex MRLs for its export purposes. NOTE: The following tolerances are listed in 40 CFR 180.447; however, there are no current registrations and thes e should be removed. (c) Tolerances with regional registrations. Tolerances with regional registration, as defined in §180.1(l) of this chapter, are established for the sum of residues of the herbicide imazethapyr, 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methyleth yl)

- 5

- oxo
- 1H

- imidazol

- 2

- yl]

- 5

- ethyl

- 3

- pyridine carboxylic acid, as its ammonium salt, and its metabolite, 2

- [4,5

- dihydro

- 4

- methyl

- 4

- (1

- methylethyl)

- 5

- oxo
- 1H

- imidazol

- 2

- yl]

- 5

- (1

- hydroxyethyl)

- 3

- pyridine carboxylic acid, both free and conjugated, applied as its acid or ammonium salt, in or on the following raw agricultural commodities: Commodity Parts per million
Endive 0.1 Lettuce, head 0.1 Lettuce, leaf 0.1