UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

### MAY 

### 2 

## 8 

# a03 WASHINGTON,D.C. 20460

OFFICE OF PREVENTION, PESTICIDES, AND TOXIC SUBSTANCES
PC Code No. 090209 DP Barcode: D274862 May 27,2003
MEMORANDUM

SUBJECT: Fenhexamid: Response to Waiver Requests for Additional Aerobic Soil Metabolism Data and Additional Fish Bioaccumulation Data

TO: Summer Gardner-Jenkins, PM Team Reviewer Mary Waller, Product Manager Registration Division (75056

FROM: Cheryl A. Sutton, Ph.D. Environmental Scientist ERB4lEFED (7507C)

THRU: Elizabeth Behl, Chief ERB4lEFED (7507C)

The Environmental Fate and Effects Division (EFED) has reviewedthetwo fenhexamid data waiver requests submitted to EPA on 412012000 on behalf of Tomen Agro, Inc. and Bayer Corporation, entitled:

0 Fenhexamid: Request for Waiver from the Requirement of Additional Aerobic Soil Metabolism Data; and

Fenhexamid: Request for Waiver from the Requirement of Additional Fish Bioaccumulation Data.
The additional datawere requiredinthe May 2 1,1999 Notice ofRegistration for Fenhexamid Technical as a condition of registration. The Notice of Registration stated that the studies were to be submitted to the Agency by June 30,2001. The new data requirements were made in response to the needs for additional data as stated in EFED's Section 3 review (dated 411 5/99; DP Barcodes D24492 1, D244932, D249057, D250286, D253050, and D254 

### 139) which was conducted for the registration of fenhexamid for use on grapes, strawberries and ornamentals. In a letter dated 4/20/2000 and received at the Agency on 4/21/2000, the registrant requested that both of the additional data requirements be waived, and provided documents in which they explained the rationale for and provided information and/or data in support of the waiver requests.Aerobic SoilMetabolism Data Waiver Request (Bayer Report #MR-157/00; Tomen Report#TMN014E-1) 

### The requirement for additional aerobic soil metabolism data followed fiom the review of MRIDs 44346729 and 44346730, submitted to fulfill data requirements under Subdivision 

### N Guideline 1 62- 1 (83 5.4 100Aerobic Soil Metabolism). In each of the studies, the parent compound was observedto degrade rapidly (DT,,'s of<1 day), while forming high levels ofbound residues (up to 6 

### 1 %

### of the applied);polymerization oftheparent was a major transformation process. Ofconcern to the previous EPA reviewer (Dr. Jim Cowles) and the PMRA reviewer (Dr. Regi Mathew), as stated in the EPA-PMRA joint review (reportedly dated February 1999),was the potential effect on residue binding resulting fiom the use of the organic solvent carrier, acetonitrile. Of particular
concern was whether the carrier solvent increases the polymerization process in the soil matrix. Based on informationprovided in the waiver request document, a condition ofregistration included the requirement for additional 1 62- 1 

### data as stated below:

"Anaerobic soil metabolism study in which fenhexamid is introducedto the testsystem via an aqueous solution to determine ifthe rapid binding in soil is facilitated by organic solvent."



### In the data waiver request, the registrant indicated that the use of acetonitrilewas necessary due to the low aqueous solubility of the compound and the limitations on the amount of water that could be added to the soil samples and still allow for the study design to meet the soil moisture requirements for the aerobic soil metabolism study under Subdivision N.

To support the waiver request, the registrant provided informationwhich indicated that the carrier solvent did not significantly affect either the formation of metabolites or the behavior (includingbinding) offenhexamid in soil as compared with thebehavior ofthe compound following applicationin aqueous solution. The submitted data was generated as a supplementary experiment in a soil photolysis study (MRID 44346728) which was also submitted to the Agency as part of the registrationpackage.

Based on the information provided by the registrant and considering the results of the submitted 162-1 studies (MRIDs 44346729 and 44346730), the EFED reviewer concurs with the registrant's conclusion that the behavior of fenhexamid in soil is understood and that a new study would not provide significant new information. Therefore, EFED recommends that the waiver request be granted.

Fish Bioaccumulation Data Waiver Request (Bayer Report #notprovided; TomenReport #TMNOOlDD) 

### The requirement for additional fish bioacuurnulation data followed from the review of MRIDs 44346746 and 44346747, submitted to fulfill data requirements under Subdivision N Guideline 165-4(850.1850 Aquatic Food ChainTransfer, Aquatic Organism Accumulation). In the study, which was done at two treatment levels, fenhexamid displayed a moderate potential tobioaccumulate in the edible portion of bluegill sunfish (BCF's of 37 and 60), and a high potential to bioaccumlate in the nonedible (BCF's of248 and 339) and whole fish tissues (BCF's of 158 and 132)of the fish. The parent compound accounted for approximately 50% and 40% of the residues found in the filet and viscera tissues, respectively. While a glucuronide was found to account for approximately 12%of the residuesin the filettissues, residues summingto 6% were not adequately characterized. Of concernto the previous EPA reviewer (Dr. Jim Cowles) and the PMRA reviewer (Dr.Regi Mathew), as stated in the EPA-PMRAjoint review (reportedly dated February 1999),was the lack of adequate characterization of the residuesinboth the water and fish tissues. It isnoted that the study was submitted in the form oftwo MRID's, the first ofwhich reportedthe BCF values while the second study contained information on fenehxamid residues in the fish tissues, obtained from
a separatestudythan that in which the BCF values were determined. Neither ofthe reports contained information on the residuesinthe test system water, as a chromatographic analysis ofwater samples was not conducted as part of either of the studies. Based on information provided in the waiver request document, a condition ofregistration included the requirement for additional 165-4 data as stated below:



### "A bioaccumulation study that adequately measures the concentration of parent and the transformation products in the test water andfish."

In the data waiver request document, the registrant indicated that fenhexamid was stable in water (i.e., in the dosing water), and provided data from an acute toxicity study conducted using a flow-through system with bluegill sunfish, as used in the bioaccumulation studies. The basic parameters (e.g., water temperature and pH; photoperiod and light conditions)were similar in the two different types of studies. The summary data from the acute toxicity study reported by the registrant demonstratethat theparent compound, detected at 93-1 0 1 %ofthenominal concentration,
was stable in such an aqueous system. It was noted in the waiver request document that the data are in agreement with other submitted data which indicate that the compound is hydrolytically stable, but do not agree with submitted data which indicate that the compound undergoes rapid photolysis. However, the lack of significantphotolysis in the acute toxicity study was attributed to the use of light of "much lower" intensity than that used in the aqueousphotolysis study.

Also in the data waiver request document, the registrant indicated that the residues in fish tissue which could not be isolated or identified were present at "low concentrations" and could not be isolated in sufficientquantity for identificationdue to a high loss ofresidues during clean-up of the tissue samples. The registrant also indicated that the single metabolite that was detected [adequatelyresolved]in HPLC chromatograms, but not identified, waspresent at low levelsthat did not allow for its isolation and [further]spectroscopic analysis. The registrant indicated that a repeat studywould be prone to the same analytical limitationsand would not result in data that contribute to a greater understanding of fenhexamid metabolites in fish tissues.

The reviewer notes that the aforementioned unidentified single metabolite was detected at levels at or approximating those at which other degradates were successfully identified. Additionally, the data table included in the waiver request document indicates that there were other residueswith known retention times which were present at levels of 20.05 ppm, the minimum level

### beyond which identification is required under Subdivision 

### N Guidelines.

Based on the information provided by the registrant and considering the results of the submitted 165-4 studies (MRIDs 44346746 and 44346747), the EFED reviewer concurs with the registrant's conclusion that the stabilityof fenhexamid in the test water is adequately demonstrated by the reported data from the acute toxicity test. However, with respect to the identification of the metabolites present in the fish tissue samples, the EFED reviewer does not concur with the registrants conclusions that fenhexamid metabolite residues in fish studiesare adequately understood and that a repeat study would not add to the present understanding of such. Therefore, EFED recommends that, with regard to the fish tissue data, the registrant be requested to either provide additionaldata to support the waiver request or, alternatively, provide the datapreviously requested
as a condition of registration.