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environmental fate and effects, this document addresses only those comments pertinent to human 

health aspects of the preliminary work plan (PWP) for flufenacet.

CONCLUSIONS/RECOMMENDATIONS

The Agency thanks Bayer CropScience for their comments regarding flufenacet. HED and BCS 

are in full agreement regarding the outstanding data requirements for Human Health Risk

Assessment. The Agency will consider all of BCS’ comments during the development of the 

final work plan for flufenacet registration review.

DETAILED CONSIDERATIONS 

Bayer CropScience to the Office of Pesticide Programs (OPP) Regulatory Public Docket 

(7502P). Registration Review docket for Flufenacet Docket Opened for Review and 

Comment. Docket Number: EPA-HQ-OPP-2010-0863. 

Bayer CropScience’s comment: As a part of this order, the EPA has recommended a separate 

group of rat pups be treated by gavage with the low dose that was tested in the DNT study 

(1.7 mg/kg/day) to determine whether thyroid endpoints are affected at this dose. The 

absence of an effect in these assays at 1.7 mg/kg/day would support this dose as a NOAEL 

(instead of a LOAEL) for the DNT study and for young animals generally.

The revised human health risk assessments for flufenacet should take into account the 

collective results from these assays, since the Agency’s judgment that the low dose of the 

DNT was LOAEL is the basis for the acute and chronic reference dose.

HED’s Response: HED agrees that, if designed and executed properly, the CTA may be 

used to confirm or refute offspring body weight effects (approximately 15% decrease in 

all dose groups) upon which the DNT LOAEL (1.7 mg/kg/day) is based. The Agency 

will consider the results from the CTA, DNT and entire toxicology database collectively 

to make a weight-of-evidence determination of toxicological effects.

Bayer CropScience’s comment: The study (860.1500) is complete and has been submitted to 

the Agency for review (MRIDs 47930801 and 48456001). Define SC is a “suspension 

concentrate” formulation of flufenacet (i.e., not a soluble concentrate or emulsifiable 

concentrate) and Define DF is a “dry flowable” formulation of this active. The SC was 

developed to enable users to pump the formulation in a closed system as opposed to pouring 

the dry flowable. Results from a “side by side” comparison study indicate that the residues 

in/on corn matrices resulting from the use of Define SC were similar to or lower than the 

residues observed in/on the same corn matrices resulting from the use of Define DF. 

Collectively, the data demonstrate that the corn tolerances as published in 40 CFR 180.527 

are adequate to support the use of either formulation on field or sweet corn at postemergence 

application timings through growth stage V5 at labeled application rates.

HED’s Response: Bayer CropScience has submitted a third bridging study to support 

postemergence application uses of the soluble concentrate (SC) formulation to the 

Agency for review. The study has been screened and, while the rationale for conducting 
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the bridging study in Kansas rather that Iowa was not provided, the data are considered 

adequate and support the results from the two earlier bridging studies, pending final

review.