EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

(7/1/2007)

EPA Registration Division contact: [insert name and telephone number with area 

code]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert “NA-Remove” and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., “[insert 

company name],” with the information specific to your action.

TEMPLATE:

[Dow AgroSciences, LLC]

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from [Dow 

AgroSciences, LLC], [9330 Zionsville Road, Indianapolis, IN, 46268] 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 180.576.

(Options (pick one)

1. to reestablish and make permanent tolerances for residues of

[the combined residues of cyhalofop (cyhalofop-butyl, R-(+)-n-butyl-2-(4(4-

cyano-2-fluorophenoxy)-phenoxy)propionate, plus cyhalofop acid, R-(+)-2-(4(4-

cyano-2-fluorophenoxy)-phenoxy)propionic acid) and the di-acid metabolite, (2R)-4-

[4-(1-carboxyethoxy)phenoxy]-3-fluorobenzoic acid] in or on the raw agricultural 

commodity [Rice, grain] at [0.35] parts per million (ppm) and [Rice, wild grain] at 

[0.35] 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 metabolism of cyhalofop-butyl in plants (rice) is 

adequately understood for the purposes of a tolerance in rice. Two separate foliar 

broadcast 14C NOR studies have been conducted. Results indicated cyhalofop-
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butyl was metabolized to cyhalofop (acid form) and then subsequently to the free 

and conjugated forms of the di-acid and the FHPBA. Other minor metabolites were 

also identified. In addition, the rotational crop study showed no carryover of 

significant cyhalofop-butyl related residues in representative crops.]

2. Analytical method. [An adequate analytical method is available for 

enforcement purposes; the method has been developed and validated to determine 

the residues of cyhalofop-butyl, cyhalofop (acid form) and the di-acid metabolite in 

rice grain, straw and processed products. The method was based on capillary gas 

chromatography with mass selective detection. Limits of detection were 0.005 or 

0.006 ppm depending on the analyte and matrix.]

3. Magnitude of residues. [The existing MOR work in rice was conducted as 18 

field trials in 1998 in the major rice-growing regions of the US. Clincher* herbicide 

(formulation XRM-5151) was applied as a foliar broadcast to established rice plants 

at proposed maximum label rates. Samples were analyzed for cyhalofop-butyl, 

cyhalofop-acid and the di-acid metabolite via GC/MSD using method GRM 99.06 

with a limit of detection (LOD) of 0.005 ug/g. No residues were detected in a 

majority of the grain samples. Residues in the grain ranged from ND to 0.02 ppm. 

Residues in the straw ranges from 0.02 to 6.14 ppm. Within the processing study 

conducted at ~ 5X the application rate, no detectable residues were noted for grain, 

bran and polished rice. 

Six more residue trials were also conducted in 2009 in the major rice growing areas 

of the country to provide updated residue data. Residues of cyhalofop-butyl and 

metabolites in grain and rice straw were determined by LC/MS/MS after two 

postemergent applications of GF-2112 or NAF-541 at a total rate of 0.47 lb ai/A. 

After treatments, cyhalofop acid residues in rice grain and straw ranged from nondetectable to 0.022 μg/g and from non-detectable to 0.788 μg/g, respectively. 

Cyhalofop diacid residues in rice grain and straw ranged from non-detectable to 

0.265 μg/g and from 0.564 to 3.33 μg/g, respectively, after treatment with NAF-541. 

These studies are also supporting uses in wild rice varieties for the minor use of 

cyhalofop in or on wild rice. Cultural practices and pest problems are similar such 

that rice data can be used for bridging data to wild rice.]

B. Toxicological Profile [The toxicological profile and endpoints for cyhalofop-butyl

which support this petition and tolerances were previously published in the Federal 

Register of June 4, 2002 (67 FRL-7178-5). The relevant information is summarized 

below.]

1. Acute toxicity. [No appropriate endpoint attributable to a single dose was 

identified; the EPA has not established an acute RfD for cyhalofop-butyl.]

2. Genotoxicty. [No evidence of genetic toxicity was observed when cyhalofopbutyl was tested in a battery of in vitro and in vivo tests.]
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3. Reproductive and developmental toxicity. [Cyhalofop-butyl did not have any 

effects on reproductive parameters at dose levels that induced treatment-related 

effects in parental rats. In addition, no teratogenic potential was demonstrated in 

either rats or rabbits at dose levels that induced maternal toxicity.]

4. Subchronic toxicity. [Sub-chronic studies on cyhalofop-butyl have been 

conducted and reviewed. No endpoint was established for dermal exposure because 

no systemic effects were observed in the 21-day dermal study in the rat at doses up 

to 1000 mg/kg/day. A short-term incidental NOAEL of 4.3 mg/kg/day was selected 

as endpoint based on subchronic feeding study in mice; this endpoint was also 

designated as conservative surrogate for inhalation exposures. However, for the 

review of a tolerance, no short-term oral, dermal or inhalation exposures are 

considered.]

5. Chronic toxicity. [A chronic reference dose (cRfD) of 0.01 mg/kg/day has 

been established based on the 18-month feeding study in mice and the application of 

an uncertainty factor of 100 (10X for interspecies extrapolation and 10X for intraspecies variation). A 1X FQPA safety factor was applied to the chronic endpoint. 

Thus in the case of cyhalofop-butyl, the cPAD = cRfD = 0.01 mg/kg/day.

At the time of initial registration, the carcinogencity studies in rats and mice showed 

no evidence of a tumorigenic response. But the agency also concluded the original 

studies did not reach a maximum tolerated dose and deemed them inadequate to 

assess carcinogenic potential (Federal Register of June 4, 2002 (67 FRL-7178-5). 

The agency recently reviewed additional information on peroxisome proliferation 

and the lack of human relevance for liver tumors formed by this mode of action.

Per HED Memorandum TXR: 0054798 dated December 20, 2007 and in accordance 

with the EPA Final Guidelines for Carcinogen Risk Assessment (March 29, 2005) 

the EPA has now has classified cyhalofop-butyl as “Not Likely to Be Carcinogenic to 

Humans”.

At the time of registration, the agency created a holding time for water based on the

original uncertainty for cancer classification coupled with estimates of drinking 

water concentrations using a modified GENEEC approach for rice paddies and 

SCI-GROW. A 7-day holding time was established to allow estimated

concentrations of cyhalofop-butyl to fall below 0.15 ppb. Based on the recent cancer 

reclassification and Table 6 of the June 4, 2002 Final Rule for Cyhalofop-butyl; 

Time-Limited Pesticide Tolerance, the 7-day holding time is not needed.]

6. Animal metabolism. [Oral administration of cyhalofop-butyl, results in 

rapid absorption, metabolism and excretion in the dog and rat. The butyl ester 

form is rapidly hydrolyzed to the acid form (cyhalofop) with no significant 

quantities of unchanged parent in the plasma, tissues or excreta.]

7. Metabolite toxicology. [In all matrices (animal, plant, environmental), 

cyhalofop-butyl is rapidly metabolized to the acid form, cyhalofop. Hence 
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mammalian toxicity studies inherently include the acid metabolite as part of the 

study. Plant studies have identified the di-acid as a major metabolite; the di-acid is 

more polar, and less lipid soluble and is expected to be less toxic than the parent.]

8. Endocrine disruption. [No evidence from any of the studies indicates 

cyhalofop-butyl is an endocrine disrupter.]

C. Aggregate Exposure

1. Dietary exposure. [Chronic exposure resulting from agricultural use of 

cyhalofop-butyl on rice has been assessed for the US population and subpopulations. The dietary assessment model DEEM-FCID version 2.16 was 

employed. It estimates US consumption patterns based on the Continuing Survey of 

Food Intake by Individuals (CSFII) and EPA/USDA translation recipes from 

August 2002. An estimate of the residue level in each food (e.g., water or rice) is 

multiplied by the average daily consumption estimate for that food. The resulting 

residue consumption estimate for each food is summed to determine the total 

estimated exposure. Exposure estimates are expressed in mg/kg body weight/day 

and compared to the cPAD.]

i. Food. [For cyhalofop-butyl, a DEEM residue file for a Tier I dietary 

assessment was prepared using the 0.35 ppm proposed tolerance for “Rice, grain”, 

“Rice, wild, grain”, for rice. The exposure was assessed against a cPAD = cRfD = 

0.01 mg/kg/day. The assessment assumes that all commodities with cyhalofop-butyl 

tolerances (i.e., rice and wild rice) contain residues of cyhalofop-butyl at the

tolerance level.

Results indicate exposure to cyhalofop-butyl residues is very low and represents less 

than 2.9 % of the cRfD for all subpopulations.]

ii. Drinking water. [The estimated drinking water concentrations (EDWCs) 

used in the dietary risk assessment were provided by the Environmental Fate and 

Effects Division (EFED). The EDWC was incorporated directly into this dietary 

assessment into the food categories “water, direct, all sources” and “water, indirect, 

all sources.”

Dietary and water exposure were chronically assessed against the cRfD of 0.01 

mg/kg/day. All subpopulations have exposure estimates of < 20.9% cPAD.]

2. Non-dietary exposure. [There are no residential uses for this compound.]

D. Cumulative Effects

[For purposes of this tolerance petition, no assumption of a common 

mechanism of toxicity for cyhalofop-butyl with other substances has been made.]
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E. Safety Determination []. 

1. U.S. population. [Based on the dietary and water exposure assessments, 

chronic dietary exposure to cyhalofop-butyl from registered uses in rice plus 

drinking water will utilize <20.9% of the cRfD for the U. S. population. Exposures 

below 100% of the cRfD are typically below the EPA’s level of concern because the 

chronic RfD represents the level at or below which daily dietary exposures over a 

lifetime will not pose appreciable risks to human health.]

2. Infants and children. [Per Federal Register of June 4, 2002 (67 FRL-7178-5), 

EPA has previously determined that an FQPA safety factor of 1X is applicable to all 

population subgroups for cyhalofop-butyl. The major identifiable subgroup with 

the highest chronic dietary exposure is “non-nursing infants” with exposure to 

estimated residues of <21 % of the cPAD. Dow AgroSciences concludes with 

reasonable certainty that no harm will result to infants and children from the 

aggregate exposure to cyhalofop-butyl residues from registered and proposed uses.]

F. International Tolerances

[A review of national websites and the Homologa MRL database indicates 

several values have been set for cyhalofop in rice globally. The proposed US value 

of 0.35 ppm in rice is higher than values in Europe and Latin America, and most of 

the Pacific. No MRLs were noted by Codex.

Argentina, Brazil, Australia, Turkey Rice 0.01 PPM

EU and various individual member 

states

Rice 0.02 PPM

Japan, South Korea and Taiwan Rice 0.1 PPM

]