EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE

PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: Kathryn Montague 703-305-1243

Bayer CropScience LLC

PP# 9F7679

EPA has received a pesticide petition (9F7679) from Bayer CropScience LLC, 2 T. W. 

Alexander Drive, Research Triangle Park, NC 27709 proposing, pursuant to section 408(d) of the 

Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C.346a(d), to amend 40 CFR part 180. 

by establishing a tolerance for residues of the herbicide safener, mefenpyr-diethyl including its 

metabolites and degradates. Compliance with the tolerance levels specified is to be determined 

by measuring residues of mefenpyr-diethyl ((RS)-1-(2,4-dichlorophenyl)-5-methyl-2-pyrazoline3,5-dicarboxylic acid) and its dichlorophenylpyrazoline metabolites] in or on the raw agricultural 

commodity [sorghum, grain] at [0.01] parts per million (ppm); [sorghum, forage] at [0.1] ppm; 

[sorghum, stover] at [0.05] ppm; [grass, hay] at [0.05] ppm; and [grass, forage] at [1.5] ppm. 

EPA has determined that the petition contains data or information regarding the elements set 

forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of 

the submitted data at this time or whether the data supports granting of the petition. Additional 

data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The nature of mefenpyr-diethyl residues in plants and livestock is

adequately understood. The residues of concern are combined residues of mefenpyr-diethyl, also

known as 1-(2,4-dichlorophenyl)-4,5-dihydro-5-methyl-1H-pyrazole-3,5-dicarboxylic acid,

diethyl ester and its 2,4-dichlorophenyl-pyrazoline metabolites.

2. Analytical method. An enforcement method for plants has been developed and

radiovalidation and independent laboratory validation (ILV) conducted. The EPA has concluded

that this method is suitable for food tolerance enforcement of mefenpyr-diethyl and its 2,4-

dichlorophenyl-pyrazoline metabolites.

M-36Ü357-Ü1-1

3. Magnitude of residues. The appropriate number of residue trials was conducted in

sorghum and grasses in the appropriate locations in the United States to support the requested

tolerances on the sorghum and grass commodities. Specifically, twelve field trials were

conducted to measure the magnitude of total mefenpyr-diethyl residues in/on sorghum forage,

grain, and stover or grass hay and forage following two foliar spray applications of HUSKIE

herbicide to sorghum or grass. Residues of mefenpyr-diethyl and 2,4-dichlorophenyl-pyrazoline

metabolites were quantified in the harvested matrices (sorghum grain, forage and fodder as well

as grass hay and grass forage) following a postemergence application of Huskie Herbicide.

The highest average field trial (HAFT) total mefenpyr-diethyl residue in sorghum forage

harvested at a 0-day PHI was 1.1 ppm (maximum residue 1.2 ppm); There were no total

mefenpyr-diethyl residues greater than the LOQ (0.10 ppm) in sorghum forage harvested at

either a target 7-day PHI or at ECH. There were no total mefenpyr-diethyl residues greater than

the LOQ (0.01 ppm) in sorghum grain. The HAFT total mefenpyr-diethyl residue in sorghum

stover was 0.06 ppm (maximum residue 0.06 ppm). The total mefenpyr-diethyl residue

decreased with time in sorghum early forage but could not be assessed in ECH forage, grain, or

stover due to residues being below the LOQ.

The HAFT total mefenpyr-diethyl residue in grass forage harvested at a 0-day PHI was 1.4 ppm
(maximum residue 1.4 ppm). The HAFT total mefenpyr-diethyl residue in grass forage harvested

at a 7-day PHI was 1.2 ppm (maximum residue 1.2 ppm). No residues greater than the LOQ of

0.05 ppm were observed in any of the hay samples harvested at a target 30-day PHI.

B. Toxicological Profile

The Agency published complete reviews of the safety of mefenpyr-diethyl in the ‘Final Rule’

published in the Federal Register April 30, 2003 (Volume 68, Number 83, Pages 23038-23046),

and in the Federal Register December 10, 2008 (Volume 73, No. 238, pages 74972- 74979).

EPA has evaluated the available toxicity data and considered its validity, completeness, and

reliability as well as the relationship of the results of the studies to human risk. EPA has also

considered available information concerning the variability of the sensitivities of major

identifiable subgroups of consumers, including infants and children.

1. Acute toxicity. Mefenpyr-diethyl has low acute toxicity by the oral, dermal, and

inhalation routes of exposure. It is not a dermal irritant but is a slight dermal sensitizer and ocular

irritant.

2. Genotoxicty. Mefenpyr-diethyl did not show any genotoxic potential.

3. Reproductive and developmental toxicity. Developmental toxicity was not observed in

the rat at the limit dose (1,000 milligrams/kilogram/day (mg/kg/day)) but was observed in the

rabbit (abortions) at the same dose level producing maternal toxicity. Mefenpyr-diethyl did not

induce any signs of reproductive toxicity or neurotoxic potential. The developmental toxicity

studies in rats and rabbits, as well as the reproductive toxicity study in rats, did not demonstrate

any prenatal or postnatal sensitivity. There was no evidence of reproductive toxicity following

exposure via the diet at concentrations of 0, 200, 1000, and 5000 ppm for two generations. There

is a lack of evidence of neurotoxicity in any study on mefenpyr-diethyl and therefore there is no

concern for neurotoxicity resulting from exposure to mefenpyr-diethyl.

4. Chronic toxicity. Repeat exposure via the dermal route did not induce any treatmentrelated

effects at dose levels up to and including the limit dose. Repeated exposure studies via

the oral route demonstrated that the target organs are the liver and hematopoietic system in dogs,

mice, and rats. Mefenpyr-diethyl was negative for carcinogenicity in rats and mice, and classified

as ``not likely to be carcinogenic to humans.''

5. Animal metabolism. Metabolism studies indicate that mefenpyr-diethyl is rapidly

metabolized, widely distributed, and primarily excreted via the urine and feces during the first 24

hours.

7. Metabolite toxicology. The metabolic profile for mefenpyr-diethyl appears to be

substantially similar in plants, animals and the environment. The primary identified metabolites

in rats, ruminants, poultry, plants and the environment are the three 2, 4-

dichlorophenylpyrazolone

metabolites which are included in the risk assessment and for tolerance setting

purposes.

C. Aggregate Exposure

1. Dietary exposure. Assessments were conducted to evaluate potential risks due to

chronic and acute dietary exposure of the U.S. population and selected population subgroups to

residues of mefenpyr-diethyl and its two 2,4-dichlorophenyl-pyrazoline metabolites. These

assessments included current and proposed uses of mefenpyr-diethyl.

Exponent Inc.'s Dietary Exposure Evaluation Model (DEEM-FCID, Version 2.14), which is

licensed to Bayer, was used to estimate the chronic and acute dietary exposure. This software

uses the food consumption data from the 1994-1998 USDA Continuing Surveys of Food Intake
by Individuals (CSFII 1994-1998).

No appropriate endpoint attributable to a single exposure (dose) was identified from oral

toxicity studies in the database. Therefore, an acute dietary endpoint was not selected and

an acute dietary risk assessment was not conducted.

The cRfD was established based on increased liver weights in the chronic dog study. The

LOAEL for this study was 260 mg/kg/day (M/F) with a NOAEL = 51.0 mg/kg/day. This

study is supported by the chronic rat study, which shows a similar NOAEL (48

mg/kg/day). Application of the normal 100X uncertainty factor results in a cRfD/cPAD

of 0.51 mg/kg/day. Results from the chronic dietary exposure analysis described below 

demonstrate a reasonable certainty of no harm to the overall U.S. population or any population

subgroup from the proposed use of mefenpyr-diethyl on sorghum and grass grown for

seed.

i. Food. The tier 1 chronic risk assessment was conducted using the results of

field trials conducted at maximum label application rates and the shortest pre-harvest

intervals on the proposed label. No adjustments were made to account for dissipation of

residues during storage, transportation from the field to the consumer, washing or

peeling. Therefore, the actual dietary exposure will be less than that presented here.

The chronic dietary exposure estimated the percent of the chronic reference dose (cRfD)

for the overall US population and various subpopulations. In this analysis, total exposure

was less then 1% of the chronic RfD for the US Population and all population subgroups.

Therefore, the chronic exposure estimates are below EPA's level of concern for the

overall U.S. population as well as all subpopulations.

ii. Drinking water. EPA’s Tier 1 EDWCs for surface and ground water were generated

using FIRST and SCIGROW, respectively. Based on the results of these simulations,

EPA recommended a chronic EDWC of 3μg/L for use in the human-health risk

assessment. Potential water residues are included in the dietary exposure calculated

above.

D. Cumulative Effects

EPA has not made a common mechanism of toxicity finding for mefenpyrdiethyl

and any other substances and mefenpyr-diethyl does not appear to produce a toxic

metabolite produced by other substances. Therefore, EPA has not assumed that

mefenpyr-diethyl has a common mechanism of toxicity with other substances. 

E. Safety Determination

1. U.S. population. Using the conservative exposure assumptions described

above and based on the completeness of the toxicity data, it can be concluded that

aggregate exposure to residues of mefenpyr-diethyl presents a reasonable certainty of no

harm. No appropriate endpoint attributable to a single exposure (dose) was identified

from oral toxicity studies in the database. Therefore, an acute dietary endpoint was not

selected and an acute dietary risk assessment was not conducted.

The chronic assessment indicated that exposure from residues in crops utilized

<1% of the chronic RfD for the U. S. Population when food and water are included. EPA

generally has no concerns for exposures below 100% of the cRfD. An aggregate

assessment for the proposed uses for mefenpyr-diethyl demonstrates that there is a

reasonable certainty that no harm will result to the US Population from these uses of

mefenpyr-diethyl.

2. Infants and children. FFDCA section 408 provides that EPA shall apply an
additional tenfold margin of safety for infants and children in the case of threshold effects

to account for pre and post natal toxicity and the completeness of the data base unless

EPA determines that a different margin of safety will be safe for infants and children. The

toxicological database for mefenpyr-diethyl is complete for FQPA purposes and there are

no residual uncertainties for pre-/post-natal toxicity for mefenpyr-diethyl. Based on the

available toxicity data the Special FQPA Safety Factor can be reduced to 1x.

Based on the exposure assessments described above and on the completeness and

reliability of the toxicity data, it can be concluded that the dietary exposure from the

proposed uses for mefenpyr-diethyl consumes <1% of the cRfD for all subpopulations.

Thus, it can be concluded that there is a reasonable certainty that no harm will result from

aggregate exposure to mefenpyr-diethyl residues.

F. International Tolerances

No Codex, Canadian, or Mexican maximum residue limits (MRLs) are

established for residues of mefenpyr-diethyl and metabolites in crop or livestock

commodities.