UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

                                                                       

	                                                       	 OFFICE OF
PREVENTION, PESTICIDES

	                                                           	           
     AND TOXIC SUBSTANCES

 

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date: May 13, 2008

SUBJECT: Fenoxaprop-p-ethyl: Bridging of toxicity data from the racemic
mixture of Fenoxaprop-ethyl (HOE 033171) to the enriched D+ isomer
Fenoxaprop-p-ethyl (HOE 046360). 

 

PC Code:  129092	DP Barcode: 351906

MRID No.:  None	Registration No.: None

Petition No.: None	Regulatory Action: None

Assessment Type: None	Reregistration Case No.: None

TXR No.:  0054851	CAS No.:  66441-23-4



	          	

FROM:  	Elissa Reaves, Ph.D., Toxicologist

	   	Reregistration Branch 2

	   	Health Effects Division (7905P)	

THROUGH:	Felecia Fort, Chief.

		Reregistration Branch 2

Health Effects Division (7905P)

		

		

TO:		Kylie Rothwell, Chemical Review Manager

		Special Review and Reregistration Division (7508P)

		

BACKGROUND

Fenoxaprop-ethyl (FE) was first registered as a racemic mixture of the
D/L isomers.  After the initial racemate registration, it was discovered
that the D isomer was more pesticidally active.  The registrants then
pursued registration of a D isomer-enriched product, fenoxaprop-p-ethyl
(FPE).  However, toxicity data for the enriched form has not been
submitted until recently during the registration review process (Spring
2007).  The scoping document for FPE was formulated and publicly
available on August 29, 2007 (Docket EPA-HQ-OPP-2007-0437-0003).  A
formal comparison of the toxicity profiles of both FE and FPE was
necessary to determine if bridging of the more robust dataset of FE
could be used in support of FPE. The Health Effects Division (HED) held
a joint HasPoc/ToxSac meeting on April 17, 2007 to determine if bridging
of FE toxicity data was appropriate for FPE (Memorandum, Kidwell May 13,
2008).  The ToxSac also determined what additional toxicity data was
required for FPE.

II.	DISCUSSION/ RESULTS 

The HasPoc/ToxSac compared both datasets and determined that FE appeared
to be slightly more toxic than FPE.  The FE dataset is robust with
studies of high confidence.  Therefore, the FE toxicity studies can be
bridged with FPE such that no chronic or reproductive studies will be
required for FPE.  However, the ToxSac suggested that since the FE
studies will likely be used in a FPE risk assessment, that the FE data
evaluation records (DERs) be updated to reflect current science
policies.  

In addition, the revised Part 158 Toxicology Data Requirements for
Conventional Pesticides 

known to operate via a PPAR-α rodent mode of action.  This rodent liver
tumor mode of action for this specific chemical class is well understood
with documented early precursor key events leading to carcinogenicity;
this class is not known to target the nervous system.  Although existing
studies for FPE are limited in that they do not specifically evaluate
neurotoxicity, the ACN/SCN study is not expected to provide more
sensitive endpoints that would be protective for risk assessment. For
example, there is both an ACN and SCN study for cyhalofop-methyl, a
similar structural compound.  The NOAEL for the ACN study was greater
than 2000 mg/kg while the NOAEL for the SCN was greater than 75/250
mg/kg [M/F], both of which were not considered “value added” for the
risk assessment.  Therefore, based on structural similarity, knowledge
of the mode of action for these compounds, and lack of neurotoxicity for
this class, the ACN and SCN studies are not required for FPE. 

 

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CONCLUSION

The FE toxicity studies may be used to bridge with FPE.  However, the
DERs for FE should be updated to reflect current HED science policies. 
Based on the revised Part 158 Toxicity Data Requirements, an
immunotoxicity study is required for FPE.  The ACN and SCN studies are
not required since the mode of action for FPE and the chemical class
does not target the nervous system.

USEPA 2005. Guidelines for Carcinogen Risk Assessment. Risk Assessment
Forum. US EPA, Washington DC. EPA/630/P-03/001F. March. 166 pp.
http://www.epa.gov/osa/mmoaframework/pdfs/CANCER-GUIDELINES-FINAL-3-25-0
5[1].pdf

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