CLODINAFOP-PROPARGYL Human Health Risk Assessment DP No. D400607

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Table of Contents

1.0 Executive Summary ........................................................................................................... 4

2.0 HED Recommendations .................................................................................................... 5

2.1 Data Deficiencies ............................................................................................................ 5

2.2 Tolerance Considerations.............................................................................................. 6

2.2.1 Enforcement Analytical Method ............................................................................... 6

2.2.2 Recommended Tolerances......................................................................................... 6

2.2.3 Revisions to Petitioned-For Tolerances.................................................................... 7

2.2.4 International Harmonization..................................................................................... 7

3.0 Hazard Characterization and Dose-Response Assessment............................................ 7

4.0 Dietary Exposure and Risk Assessment........................................................................... 8

Appendix A. International Tolerances..................................................................................... 12

Appendix B. Summary of Endpoints, Points of Departure, and Toxicology Data 

Requirements for Clodinafop-Propargyl.................................................................................. 13
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1.0 Executive Summary

Syngenta Crop Protection, LLC, jointly with Syngenta Crop Protection Canada, Inc., has 

submitted a petition to amend the established tolerance for clodinafop-propargyl on wheat grain 

from 0.1 ppm to 0.02 ppm. Syngenta has proposed using Method REM 138.10, which 

determines the metabolite clodinafop only, as the enforcement method. Method REM 138.10 is 

the current US enforcement method for the metabolite clodinafop. Method REM 138.01 is the 

current enforcement method for the parent. The LOQs in wheat grain are 0.05 ppm for 

clodinafop-propargyl and 0.02 ppm for clodinafop (D267870, N. Dodd, 8/8/00).

A tolerance was established (D246730, N. Dodd, 4/7/00; D324689, N. Dodd, 3/30/06) for 

combined residues of clodinafop-propargyl and its metabolite clodinafop at 0.1 ppm in wheat 

grain. Tolerances were also established on wheat forage and wheat hay at 0.1 ppm and wheat 

straw at 0.5 ppm (40 CFR 180.559). The tolerances were based on the limits of quantitation 

(LOQs) of the methods since residues in grain were all less than the LOQs. No tolerances other 

than those on wheat commodities have been established for clodinafop-propargyl.

The lower tolerance of 0.02 ppm will harmonize with the maximum residue limit proposed for 

the European Union (EU) by the European Food Safety Authority (EFSA). The EFSA has 

proposed residues of the metabolite clodinafop only as the residue of concern since residues of 

parent are not expected to occur in wheat grain. No request has been made to change the 

established tolerances on wheat forage, wheat hay, or wheat straw.

The US registered end-use products are Discover® Herbicide (EPA Reg. No. 100-907) and 

Discover® NG Herbicide (EPA Reg. No. 100-1173). Discover Herbicide®contains 2 lb 

ai/gallon. Discover® NG Herbicide contains 0.5 lb ai/gallon. One postemergence broadcast 

foliar application is made at the rate of 3.2-4 oz Discover® Herbicide/A (0.05-0.06 lb ai/A) or 

12.8-16 oz Discover® NG Herbicide/A (0.05-0.06 lb ai/A). Preharvest intervals (PHIs) are 30 

days for forage and hay, and 60 days for grain and straw.

Syngenta Crop Protection, LLC has submitted a new analytical method using high performance 

liquid chromatography with tandem mass spectrometry detection (LC/MS/MS), Enviro-Test 

Laboratories Report No. MS 247, for the determination of residues of clodinafop-propargyl 

(CGA-184927) and its metabolite clodinafop (CGA-193469) in/on wheat forage, grain, and 

straw. The method is adequate for determination of residues of clodinafop-propargyl and its 

metabolite clodinafop in wheat grain at 0.02 ppm (i.e., 0.01 ppm for each analyte).

Also, Syngenta Crop Protection, LLC, has submitted field trial data for clodinafop-propargyl on 

wheat. Twenty field trials were conducted in Canada during the 2001 growing season in the 

North American Free Trade Agreement (NAFTA) Growing Zones 5 (MB; 2 trials), 7 (AB and 

SK; 7 trials), 7A (AB; 1 trial), and 14 (AB, SK, and MB; 10 trials). Field trial data show <0.02 

ppm of residues in wheat grain.

Since the last human health risk assessment, three toxicity studies have been submitted and

reviewed: acute neurotoxicity (ACN, MRID 46012922), subchronic neurotoxicity (SCN, MRID

46012921), and developmental neurotoxicity (DNT, MRID 47085301). 
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2.0 HED Recommendations

Provided Syngenta proposes use of Method MS 247 as an enforcement method for the combined 

residues of clodinafop-propargyl and clodinafop on wheat grain, HED recommends for the 

reduction of the established clodinafop-propargyl tolerance on wheat grain from 0.1 ppm to 0.02 

ppm. HED will retain both the parent clodinafop-propargyl and the metabolite clodinafop as 

residues of concern for the tolerance expression. 

Syngenta has not proposed Method MS 247 as an enforcement method because the lowest level 

of method validation (1.0 ppb for each analyte) may not be reproducible in all laboratories. 

However, EPA has determined that Method MS 247 is adequate as an enforcement method for 

determination of residues of clodinafop-propargyl and its metabolite clodinafop in wheat grain at 

0.02 ppm (i.e., 0.01 ppm for each analyte). The method is also adequate as a data collection 

method based on adequate fortified control sample recoveries.

According to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. Knizner), the 

tolerance expressions for clodinafop-propargyl in 40 CFR §180.559 should be revised as follow:

Under 40 CFR §180.559(a): “Tolerances are established for clodinafop-propargyl, 

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 clodinafop-propargyl [(2R)-2-[4-[(5-chloro-3-fluoro-2-

pyridinyl)oxy]phenoxy]propanoic acid, 2-propynyl ester] and its metabolite clodinafop 

[(2R)-2-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenoxy]propanoic acid].”

2.1 Data Deficiencies

The following deficiencies relevant to wheat grain remain outstanding as conditions of 

registration:

Toxicology

870.7800 Immunotoxicity

An immunotoxicity study is required under 40 CFR §158.500.

Residue Chemistry

860.1300 Nature of the Residue - Livestock

The requirement from the 04/07/2000 review for additional information pertaining to the goat 

metabolism study has not been addressed by the petitioner. The petitioner must submit 

information pertaining to the time from sampling to final analysis for milk and tissue samples for 

the ruminant metabolism study reported in MRIDs 44399204 and 44399205. The petitioner 

should note that if the time between sampling and final analysis of the samples exceeded six 

months, evidence should be provided that the identity of residues did not change during the 
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period between collection and final analysis. 

860.1380 Storage Stability

The requirement from the 4/7/00 review for additional information to support the study reported 

in MRID 44399210 (storage stability of CGA-193469 in wheat grain) has not been addressed by 

the petitioner. The petitioner must submit the following additional data to support the study: (1) 

raw data, including residues (ppm) found and representative chromatograms (for standards, 

controls, freshly fortified samples, and stored samples); (2) description of storage containers; and 

(3) submission or identification by number of the method used to analyze the storage stability 

samples. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Method MS 247 (MRID 48693701) is a high performance liquid chromatography method with 

tandem mass spectrometry detection (LC/MS/MS) for the determination of residues of 

clodinafop-propargyl (CGA-184927) and its metabolite clodinafop (CGA-193469) in/on wheat 

forage, grain, and straw. Since Method MS 247 determines only one ion transition for each 

analyte, a confirmatory method is needed. The enforcement methods (REM 138.01 for parent 

and REM 138.10 for the metabolite) can serve as confirmatory methods for Method MS 247 on 

wheat grain since they use a different detection system [high performance liquid 

chromatography/ultraviolet detection (HPLC/UV)]. Recovery data at the lowest fortification 

level (1 ppb) was acceptable (i.e., within the range of 70-120%). The limit of detection (LOD) 

was set at 0.5 ppb for each analyte in wheat grain, forage, and straw, based on a signal to noise 

ratio (S/N ratio) of >3:1. The method is adequate as an enforcement method for determination of 

residues of clodinafop-propargyl and its metabolite clodinafop in wheat grain at 0.02 ppm (i.e., 

0.01 ppm for each analyte).

2.2.2 Recommended Tolerances

According to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. Knizner), the 

tolerance expression for clodinafop-propargyl in 40 CFR §180.559 should be revised as follow:

Under 40 CFR §180.559(a): “Tolerances are established for clodinafop-propargyl, 

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 clodinafop-propargyl [(2R)-2-[4-[(5-chloro-3-fluoro-2-

pyridinyl)oxy]phenoxy]propanoic acid, 2-propynyl ester] and its metabolite clodinafop 

[(2R)-2-[4-[(5-chloro-3-fluoro-2-pyridinyl)oxy]phenoxy]propanoic acid], expressed as 

the stoichiometric equivalent of clodinafop-propargyl.”

Table 2.2.2. Tolerance Summary for Clodinafop-propargyl

Commodity Established/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

Wheat, grain 0.10 0.02
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2.2.3 Revisions to Petitioned-For Tolerances

The US tolerance expression will continue to contain both parent clodinafop-propargyl and the 

metabolite clodinafop as residues of concern.

2.2.4 International Harmonization

A Codex Sheet is attached. A tolerance is established in Canada for residues of parent and the 

metabolite clodinafop on wheat at 0.1 ppm. No Codex MRLs are established for clodinafoppropargyl. The European Union has proposed a tolerance of 0.02 ppm on wheat grain, to be 

determined as clodinafop.

3.0 Hazard Characterization and Dose-Response Assessment

Clodinafop-propargyl exhibits low acute mammalian toxicity via oral (Toxicity Category III), 

dermal (Toxicity Category III), and inhalation (Toxicity Category IV) routes of exposure. 

Clodinafop is not an eye or skin irritant but is a dermal sensitizer. The primary target organ of 

toxicity is the liver in dogs, mice, and rats in subchronic and chronic studies. Skin lesions were 

observed in dogs during subchronic and chronic exposure. The most recent human health risk 

assessment of clodinafop-propargyl (D264702, A. Lowit, 05/15/00) considered the entire 

toxicology database and retained the FQPA safety factor, in part, for neurotoxicity data 

deficiencies. Since then, a neurotoxicity screening battery and a developmental neurotoxicity 

study have been submitted. The acceptable/guideline neurotoxicity studies have been reviewed 

but not incorporated into the endpoint selection for risk assessment for this action. 

A brief summary of clodinafop-propargyl neurotoxicity studies follows: 

Acute neurotoxicity (ACN), MRID 46012922: There was evidence of acute neurotoxicity 

in the form of demyelination of the tibial (distal and proximal) and sciatic (proximal) 

nerves in rats administered a single bolus dose of 300 mg/kg [ACN lowest observed 

adverse effect level (LOAEL)] and higher. NOAEL = 100 mg/kg; 

Subchronic neurotoxicity (SCN), MRID 46012921: When rats were administered 83.6 

mg/kg/day (highest dose tested) in the diet for 90 days, no treatment-related effects on 

brain weight or morphometrics, nervous tissue histopathology or neurobehavior were 

observed. The SCN LOAEL in male rats is 78.7 mg/kg/day and is based on an 11-13% 

decrease in body weight and decreased food consumption and utilization. The SCN 

LOAEL in females is greater than 83.6 mg/kg/day. NOAEL = 9.3 mg/kg/day in males 

and 86.3 mg/kg/day in females;

Developmental neurotoxicity (DNT), MRID47085301: No maternal toxicity was 

observed in the DNT but an offspring LOAEL was established at 44 mg/kg/day based on 

decreased body weight gain, increased liver weight, and decreased auditory response on 

PND 23 and increased thickness of the corpus callosum in females in PND 63. NOAEL 

= 9.0 mg/kg/day.

HED has determined that the results of the neurotoxicity studies adequately elucidate the hazard 

and will not increase the risk associated with clodinafop-propargyl exposure. The current points 
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of departure (PoD) for clodinafop-propargyl risk assessment are protective of all effects, 

including neurotoxicity, observed in the ACN, SCN and DNT submitted since the last risk 

assessment (D264702, A. Lowit, 05/15/00). The ACN no observed adverse effect level 

(NOAEL), 100 mg/kg, is 4 times greater than the current dose and endpoint selected for an aRfD 

(based currently on mortality and clinical signs of toxicity in the rabbit developmental study). 

The current acute dietary PoD for females 13-49 years is 5 mg/kg and nearly ten times less than 

the dose eliciting any effect in pups exposed perinatally to clodinafop-propargyl (DNT LOAEL 

= 44 mg/kg/day). The SCN and DNT NOAELs, both approximately 9 mg/kg/day, are two- and 

ten-fold greater than the current dose and endpoint selected for the short- and intermediate-term 

inhalation exposure scenarios, respectively. 

Developmental toxicity was observed in rats following in utero exposures but not in the rabbits 

administered clodinafop-propargyl. There was no evidence of reproductive toxicity. Toxicity to 

the offspring was seen in the DNT. There is also evidence of neurotoxicity in the recently 

submitted ACN and DNT studies. Clodinafop-propargyl is classified “Suggestive Evidence of 

Carcinogenic Potential” but quantification of carcinogenic potential is not required based on 

adequate data on the mode of action for hepatocarcinogenesis in mice. Clodinafop-propargyl is 

negative for mutagenicity in a battery of genotoxicity studies.

Absent a functional immunotoxicity study, there is evidence in the database that clodinafoppropargyl may perturb immune function. In a subchronic oral toxicity study in rats, a treatmentrelated 37% decrease in thymus weight was observed and accompanied by an increased 

incidence of thymic atrophy. Thymus effects were observed only in males, only at the highest 

dose tested (71 mg/kg/day) and fully reversed after a 4 week recovery period. No thymus effects 

were noted in the chronic toxicity/carcinogenicity study in rats. And no other indicators of 

structural immunotoxicity were observed elsewhere in the toxicology database. While an 

immunotoxicity study is required to complete the clodinafop-propargyl database in accordance 

with the 2007 revised 40 CFR §158 toxicology data requirements, this data gap will not increase 

the risk associated with clodinafop-propargyl exposure. 

4.0 Dietary Exposure and Risk Assessment 

A dietary risk assessment was not conducted, as there have been no changes in the dietary intake 

values since the last assessment. The present action lowers the tolerance for wheat grain from 0.1 

to 0.02 ppm, and this change would have no significant effect on the dietary exposure.

An analytical method (MS 247) and field trials on wheat were submitted to support the proposed 

reduction in tolerance level for wheat grain from 0.1 ppm to 0.02 ppm. Syngenta has not 

proposed Method MS 247 as an enforcement method because the lowest level of method 

validation (1.0 ppb for each analyte) may not be reproducible in all laboratories. 

860.1340 Residue Analytical Method (MRID 48693701)

Syngenta Crop Protection, LLC has submitted an analytical method description and validation 

data for a high performance liquid chromatography method with tandem mass spectrometry 

detection (LC/MS/MS), Enviro-Test Laboratories Report No. MS 247, for the determination of 
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residues of clodinafop-propargyl (CGA-184927) with its metabolite CGA-193469 and 

cloquintocet-mexyl (CGA-185072) with its metabolite CGA-153433 in/on wheat forage, grain, 

and straw. The method was used for data collection in the wheat crop field trials reviewed under 

DP# D399618 (MRID 48693702).

Briefly, homogenized samples of wheat forage, grain, and straw are extracted twice with 80% 

acetone/water, buffered to a pH of 3 using citric acid. After centrifuging and bringing to volume, 

one aliquot is taken for the analysis of clodinafop-propargyl, cloquintocet-mexyl, and CGA193469. The aliquot is purified by two solid phase extraction (SPE) clean-up steps in a series 

(C18 SPE and Envi-Carb SPE), concentrated using nitrogen, reconstituted in 20% acetonitrile/

0.1% formic acid/water, and analyzed by liquid chromatography with tandem mass spectrometry 

(LC/MS/MS). A second aliquot is taken for analysis of CGA-153433 only. The aliquot is 

purified by selective liquid/liquid partitions with 8:2 hexane/ether and ethyl acetate, concentrated 

using nitrogen, reconstituted in phosphate/water (pH 7), and cleaned-up by C18 SPE. Samples 

are then evaporated to dryness, reconstituted in 20% acetonitrile/0.1% formic acid/water, and 

analyzed by LC/MS/MS.

The method monitors one ion transition for each analyte: m/z 350→266 for clodinafoppropargyl, m/z 312→266 for CGA-193469, m/z 336→238 for cloquintocet-mexyl, and m/z

238→192 for CGA-153433. Since only one ion transition was monitored for each analyte, a 

confirmatory method is needed for the method to be an enforcement method. The current 

HPLC/UV enforcement methods (REM 138.01 for parents and REM 138.10 for metabolites) can 

serve as confirmatory methods for wheat grain.

Recovery data at the lowest fortification level (1 ppb) was acceptable (i.e., within the range of 

70-120%). The limit of detection (LOD) was set at 0.5 ppb for each analyte in wheat grain, 

forage, and straw, based on a signal to noise ratio (S/N ratio) of >3:1.

The method was adequately validated by Enviro-Test Laboratories using samples of wheat grain, 

forage, and straw fortified with each analyte at 1.0, 5.0, and 10.0 ppb (1x to 10x the LOQs). 

Overall average recoveries were 80-115% (standard deviation of 5.4-6.8%) for clodinafoppropargyl, 75-78% (standard deviation of 5.1-9.7%) for CGA-193469, 73-111% (standard 

deviation of 5.9-11.1%) for cloquintocet-mexyl, and 87-111% (standard deviation of 4.5-12.3%) 

for CGA-153433. 

Radiovalidation data were not submitted as part of the study; however, radiovalidation data have 

been conducted for Methods REM 138.01, REM 138.06, REM 138.10, and REM 138.12 

(D324689, N. Dodd, 3/30/06). Methods 138.01 and 138.12 use acetonitrile to extract parent 

residues of clodinafop-propargyl and cloquintocet-mexyl (acetonitrile was also used in the 

metabolism studies). Method REM 138.06 uses an acetone buffer at pH 3 to determine the 

metabolites CGA-193469 and CGA-153433. Method REM 138.10 uses an acetone:citrate buffer 

(8:2, v:v) to extract CGA-193469 and CGA-153433. Method MS 247 uses 80% acetone/water, 

buffered to a pH of 3 using citric acid, to extract parents and metabolites. While acetonitrile was 

used to extract clodinafop-propargyl and cloquintocet-mexyl, acetone and acetonitrile are both 

aprotic polar solvents of similar polarity and are expected to show similar extraction efficiencies. 
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Therefore, the previously submitted radiovalidation data are adequate to support MS 247 for both 

the parents and the metabolites. 

Adequate method validation data have been submitted by Enviro-Test Laboratories in MRID 

48693701 and by Syngenta as concurrent recovery data in MRID 48693702. No additional 

method validation data are required.

Conclusions: The analytical method test data for Method MS 247 are classified as scientifically 

acceptable. The method is adequate as a data collection method based on adequate fortified 

control sample recoveries. The method is also adequate, when used in combination with the 

HPLC/UV methods as confirmatory methods, as an enforcement method for determination of 

residues of clodinafop-propargyl and its metabolite clodinafop in wheat grain at 0.02 ppm (i.e., 

0.01 ppm for each analyte).

 

860.1500 Crop Field Trial Data on Wheat (MRID 48693702)

Syngenta Crop Protection, LLC, has submitted field trial data for clodinafop-propargyl on wheat. 

Twenty field trials were conducted in Canada during the 2001 growing season in the North 

American Free Trade Agreement (NAFTA) Growing Zones 5 (MB; 2 trials), 7 (AB and SK; 7 

trials), 7A (AB; 1 trial), and 14 (AB, SK, and MB; 10 trials). The submission also includes data 

for cloquintocet-mexyl. Refer to 48693702.de2 for data pertaining to cloquintocet-mexyl.

A number of trials in each Zone were conducted by the same Principal Field Investigator (PFI). 

Based on examination of the field trial records, HED concludes that each of the following trial 

groups constitutes a single trial with replicate samples for purposes of OCSPP 860.1500 data 

requirements:

MB trials T119 and T120; only difference = variety.

AB trials T129 and T130; no differences.

SK trials T124 and T125; only difference = variety.

AB trials T134, T135, T136; no differences.

With the classification of these trials as replicates, the number of separate trials for purposes of 

OCSPP 860.1500 data requirements is adjusted to 15, with 1 trial conducted in Zone 5, 6 trials 

conducted in Zone 7, and 7 trials conducted in Zone 14.

Each trial consisted of one untreated plot and one or two treated plots; separate plots were 

established for the harvest of forage (5 trials) and for the harvest of grain and straw (all trials). 

At each trial location, the treated plots received one foliar broadcast application of an 

emulsifiable concentrate (EC) formulation containing clodinafop-propargyl at 2 lb ai/gal (240 g 

ai/L) and the safener cloquintocet-mexyl at 0.5 lb/gal (Horizon 240 EC). Only data pertaining to 

clodinafop-propargyl are reviewed herein; therefore, the product will be referred to herein as the 

2 lb ai/gal EC formulation. Each treated plot received one application of clodinafop-propargyl at 

0.062 lb ai/A (70 g ai/ha). Applications were targeted at the 3-6 leaf growth stage. Applications 

were made using ground equipment; spray volumes were not reported. A crop oil 

concentrate/nonionic surfactant (COC/NIS) blend (Score) was added to the spray mixtures for all 

applications. Samples of forage were harvested from five trials (T119, T124, T127, T137, and 
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T138) at preharvest intervals (PHIs) of 5-13 days; grain and straw were harvested at maturity 

(PHIs of 62-110 days). Additional forage samples were harvested at PHIs of 3, 7, and 16 days 

from one trial (in MB) to assess residue decline. 

Samples were analyzed for residues of clodinafop-propargyl and its acid metabolite (CGA193469) using a liquid chromatography method with tandem mass spectrometry detection 

(LC/MS/MS), Method MS 247. The limit of quantitation (LOQ; determined as the lowest level 

of method validation, LLMV) was 1 ppb for each analyte. The method was adequate for data 

collection based on acceptable concurrent recovery data. The fortification levels used in 

concurrent method recovery were adequate to bracket expected residue levels. Concurrent 

recoveries and treated samples were not corrected for residues in controls. HED notes that the 

analytical method does not specify conversion of metabolite residues to parent equivalents; 

therefore, quantifiable residues of CGA-193469 were converted to parent equivalents by the 

study reviewer using a molecular weight conversion factor of 1.12 (MW of clodinafop-propargyl 

349.74 ÷ MW of CGA-193469 311.69).

Samples were stored frozen (~ -25 °C at the analytical laboratory) from collection to analysis for 

187-240 days (6.1-7.9 months) for forage, 70-114 days (2.3-3.7 months) for grain, and 103-192 

days (3.4-6.3 months) for straw. All samples were analyzed within 15-90 days of extraction. 

The available storage stability data support the storage conditions and intervals of samples from 

the submitted wheat field trials. Although previously submitted storage stability data indicate the 

potential for some decline of clodinafop-propargyl residues in wheat grain and straw samples 

over the storage intervals used in this study, no correction will be applied because the expected 

decline would be small, and residues of clodinafop-propargyl were below the LOQ in all grain 

and straw samples. 

Following one foliar broadcast application of the 2.0 lb ai/gal EC formulation of clodinafoppropargyl at 0.062 lb ai/A (70 g ai/ha), residues of clodinafop-propargyl, CGA-193469, and 

combined residues, respectively, in/on forage were: <1.0-2.5 (<1.0-<1.8), <1.0-8.8 (<1.0-8.5), 

and <2.0-<10 (<2.0-<9.5) ppb at the 5-13-day PHI. Corresponding residues in/on grain and 

straw harvested at PHIs of 62-110 days following one application at 0.062 lb ai/A (70 g ai/ha) 

were all <LOQ.

The residue decline results indicate that combined residues of clodinafop-propargyl and CGA193469 in/on wheat forage decreased with increasing PHI. 

Conclusion: The submitted field trial data are adequate to support the request for reduction of 

the tolerance for clodinafop-propargyl on wheat grain from 0.1 ppm to 0.02 ppm.

Attachments: 

Appendix A. International Tolerances

Appendix B. Summary of Endpoints, Points of Departure, and Toxicology Data Requirements
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Appendix A. International Tolerances

Clodinafop-propargyl (125203; 09/21/2012)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex

40 CFR §180.559: clodinafoppropargyl (propanoic acid, 2-[4-(5-

chloro-3-fluoro-2-

pyridinyl)oxy]phenoxy]-, 2-propynyl 

ester, (2R)-) and its acid metabolite 

(propanoic acid, 2-[4-[(5-chloro-3-

fluoro-2-pyridinyl)oxy]phenoxy]-, 

(2R)-) 

2-propynyl (2R)-2-[4-[(5-

chloro-3-fluoro-2-

pyridinyl)

oxy]phenoxy]propanoate, 

including the metabolite 

(2R)-2-[4-[(5-chloro-3-

fluoro-2-

pyridinyl)oxy]phenoxy]pr

opanoic acid

None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Wheat, grain 0.02 0.1 wheat

Completed: M. Negussie; 09/21/2012

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
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Appendix B. Summary of Endpoints, Points of Departure, and Toxicology Data 

Requirements for Clodinafop-Propargyl

Table 4. Summary of Toxicological Doses and Endpoints for Clodinafop-propargyl for Use in Dietary and NonOccupational Human Health Risk Assessments (A. Lowit, D264702, 05/15/2000)

Exposure/

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(Females 13-49 

years of age)

NOAEL = 5 

mg/kg.

UFA = 10x

UFH = 10x

FQPA SF = 10x

aPAD = 0.005 

mg/kg/day

Developmental Toxicity Study in Rats. 

Increased incidence of bilateral 

distension and torsion of ureters, 

unilateral 14th ribs and incomplete 

ossification of metacarpals and cranial 

bones at 40 mg/kg. 

Acute Dietary 

(General 

Population)

NOAEL= 25 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

aPAD = 0.25 

mg/kg/day

Developmental Toxicity Study in 

Rabbits. Mortality and clinical signs 

of toxicity were seen on Day 2 of 

dosing.

Chronic Dietary (All 

Populations)

NOAEL= 0.03

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 10x

cPAD = 0.00003 

mg/kg/day

Chronic Toxicity/Carcinogenicity 

Study in Rats. Hepatocytic 

hypertrophy, chronic progressive 

nephropathy and tubular pigmentation 

at 0.3 mg/kg/day.

Incidental Oral This risk assessment is not required. There are no residential uses of clodinafop-propargyl

Dermal (Short- and 

Intermediate-Term)

NOAEL = 50 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

MOE = 100

Dermal Toxicity in Rats. Increased 

liver weight and clinical signs 

including piloerection and hunched 

posture at 200 mg/kg/day.

Inhalation (ShortTerm)

NOAEL = 5 

mg/kg/day.

UFA = 10x

UFH = 10x

FQPA SF= 1x

MOE = 100

Developmental Toxicity Study in Rats. 

Increased incidence of bilateral 

distension and torsion of ureters, 

unilateral 14th ribs and incomplete 

ossification of metacarpals and cranial 

bones at 40 mg/kg/day.

Inhalation 

(Intermediate-Term)

NOAEL = 0.9 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF= 1x

MOE = 100

Subchronic Toxicity Study in Rats. 

Increased liver weight and enzyme 

activity at 8.2 mg/kg/day.

Cancer (oral, 

dermal, inhalation)

Classification: "Suggestive Evidence of Carcinogenic Potential". The quantification of 

carcinogenic potential is not required.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose. N/A = not applicable.