UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON D.C., 20460
                                   OFFICE OF
                              CHEMICAL SAFETY AND
                             POLLUTION PREVENTION
                                   OFFICE OF
                              CHEMICAL SAFETY AND
                             POLLUTION PREVENTION



                                                           DP Barcode:  D424686
                                                               PC Code:  128968
                                                       Date:  February 19, 2015

MEMORANDUM


Subject:	EFED's Response to Comments on the Problem Formulation for Fluroxypyr-MHE

To:		Neil Anderson, Branch Chief
		Benjamin Askin, Chemical Review Manager
		Risk Management and Implementation Branch I
		Pesticide Re-evaluation Division

Through:	Dana Spatz, Branch Chief
		Environmental Risk Branch III
		Environmental Fate and Effects Division

From:		Nicholas Mastrota, Wildlife Biologist
		Rochelle F. H. Bohaty, Chemist
		Environmental Risk Branch III
		Environmental Fate and Effects Division

Peer Review:	Rosanna Louie-Juzwiak, RAPL
		Environmental Risk Branch III
		Environmental Fate and Effects Division



This memo communicates the response of the Environmental Fate and Effects Division (EFED) to comments received from Dow AgroSciences (DAS) on the Problem Formulation for the Registration Review of fluroxypyr-methylheptyl ester (PC Code 128968).  

Comment #1 (Page 3): 
DAS agrees that the LOQ of fluroxypyr-MHE residues in water (0.05 μg/L) [MRID 48581303] is sufficient considering the current toxicological endpoints of terrestrial plants.  An independent laboratory validation for this water method is available and will be submitted upon request.

EFED Response #1:
EFED would like to obtain this independent laboratory validation of the analytical method for measuring fluroxypyr-MHE in water.

Comment #2 (Page 4): 
Data on the effects of fluroxypyr-MHE on the growth of Navicula can be taken from this study previously submitted:  Fluroxypyr-MHE "Hoberg, J (2002). Fluroxypyr 1-mepthylheptyl ester technical  -  acute toxicity to the freshwater diatom (Navicula pelliculosa).  Springborn Smithers Laboratories.  DowAgroSciences Study No. 021041. Unpublished report. MRID 45820801".


EFED Response #2:
The 2002 freshwater diatom study, MRID 45820801, was inadvertently excluded from the review of ecotoxicity data in the problem formulation document. An EFED review of this study has identified numerous serious deficiencies:

The number of replicates per treatment level (3) is less than recommended (4).
The dilution water characteristics were not reported.	
Cell growth in the solvent control was significantly greater than in the negative control, indicating that the solvent (DMF) enhanced growth of the diatoms.
Cell growth was very inconsistent among replicates within a treatment group, and mean cell growth did not follow a consistent dose-response among the treatment groups.
The test material, fluroxypyr-MHE, transformed into fluroxypyr acid at different rates in different test concentrations. At lower test concentrations, the transformation to the acid was nearly total by the end of the 5-day study. At the highest test concentrations, in which all of the diatoms were killed, very little transformation occurred. The intermediate test concentrations, 0.30 and 0.71 mg a.i./L, had intermediate rates of transformation. As the toxicity of the fluroxypyr acid is likely different than that of fluroxypyr-MHE, this inconsistent transformation may have impacted the study results. 
The 120-hour recovery for the measured 0.17 (68%), 0.30 (59%) and 1.3 (63%) ppm treatment groups was less than 70% of the nominal 0.25, 0.50 and 2.0 ppm treatment groups, respectively.

Consequently, this study was classified as INVALID. A new study is still needed to provide acceptable toxicity data for this species.


Comment #3 (Page 5): 
Dow AgroSciences has also conducted a study with fluroxypyr-acid and Navicula and this is available for review by EFED at request. "Hoberg, J (2002). Fluroxypyr  -  growth inhibition test with the freshwater diatom (Navicula pelliculosa).  TERC.  DowAgroSciences Study No. 031132. Unpublished report".

EFED Response #3:
EFED would like to receive this freshwater diatom study with fluroxypyr-acid for review. 


Comment #4(Page 5): 
Data has been reviewed by EFED on several studies conducted by Mohr et al., 2013. DowAgroSciences would like to highlight that these studies were conducted on fluroxypyr acid. Hence the values used in EFED review are mg a.e./L. Furthermore this paper evaluates a range of study designs and exposes plants at different growth stages; careful comparisons and conclusions should be made from the results of these studies containing fluroxypyr-acid.

EFED Response #4:
The studies reported in Mohr et al., 2013 do appear to have been conducted with fluroxypyr acid. EFED incorrectly reported the results as mg a.i./L rather than mg a.e./L. The discussion of these results on page 26 of the Problem Formulation, and the presentation of the results in Table IV.1, will be revised accordingly in the Preliminary Risk Assessment.

Comment #5 (p. 5): 
Dow AgroSciences has conducted water milfoil (Myriophyllum spicatum) studies with fluroxypyr-MHE and fluroxypyr acid and these are available for review by EFED. These studies were conducted in water/sediment systems where the water column was spiked with the test material.  The method that was followed at the time these studies were conducted is now a published OECD Guideline (No. 239). "Gonsior, G. (2013). Fluroxypyr-meptyl - Growth inhibition of Myriophyllum spicatum in a water/sediment system. Eurofins AgroScience Services EcoChem GmbH. DAS Study no. 120747. Unpublished report."  Also "Gonsior, G. (2012). Fluroxypyr - Growth inhibition of Myriophyllum spicatum in a water/sediment system. Eurofins AgroScience Services EcoChem GmbH. DAS Study no. 120748. Unpublished report".

EFED Response #5:
These studies of the toxicity of fluroxypyr-MHE and fluroxypyr acid to milfoil would be useful for the risk assessment of fluroxypyr-MHE.  EFED would like to receive both of these studies.

Comment #6 (page 5): 
Data on acute oral toxicity of fluroxypyr-MHE to adult honeybees can be taken from the following study previously submitted. The 48-hour oral LD50 value is > 100 ug/bee indicating low toxicity to adult honeybees. "Cole, J (1983).  The acute contact and oral toxicity to honeybees of technical Dowco 433  -  MH ester: laboratory project ID: DWC 387/73717/2. Unpublished study prepared by Huntingdon research centre. (MRID 40244527)"

EFED Response #6:
As shown in Table VI.3 of the Problem Formulation, EFED reviewed the honey bee study MRID 40244527 and classified it as Supplemental. According to the Data Evaluation Record for this study, the study methods deviated significantly from the recommended protocol, and some important information about the study methods were not reported. The newer honey bee study, MRID 42137313, which was classified as Acceptable, will therefore be used for assessing risk to bees.

Comment #7 (pages 6-7): 
Conducting [the chronic oral toxicity study with adult honeybees] is unlikely to provide more information for the pollinator risk assessment due to the lack of toxicity and sublethal effects observed in the acute oral study with adult honeybees... [The chronic oral toxicity study with honeybee larvae is not needed because] the toxicity of fluroxypyr-MHE to the larvae is likely to be very low based on known toxicity of this active to adult honeybees via both the oral and contact routes of exposure.  Without a published guideline and laboratories experienced in conducting these studies, results maybe variable and unreliable.

EFED Response #7:
A June 23, 2014 guidance memorandum titled, Guidance for Assessing Pesticide Risk to Bees, advises that chronic oral toxicity tests with adult and larval honey bees are needed as tier-1 screening-level tests for all pesticides that have uses that could result in exposure to bees. Similar to other taxa evaluated by EPA, the chronic testing requirements for bees are not contingent on results observed in acute tests. Use of fluroxypyr-MHE is expected to result in some oral exposure to bees. Therefore, these studies are considered necessary.

While formal test guidelines are not currently available for these studies, guidance for conducting chronic oral testing of adult and larval honey bees is available, including a draft OECD guideline for a honey bee larval test with repeated doses. Several testing laboratories also have experience with conducting these types of tests and have submitted both 10-day adult and 21-day larval toxicity tests in support of registration. EPA recommends that proposed protocols for conducting these tests be submitted for review and comment before the tests are initiated. 

Comment #8 (page 6): 
There is low toxicity of fluroxypyr-meptyl to adult honeybees observed in the acute contact studies (100 ug/bee and >25 ug/bee) and so exposure via foliage residues of fluroxypyr-meptyl is also likely to be practically non-toxic. 

EFED Response #8:
We agree with the DAS's comment. Since there is an acceptable acute contact study showing that fluroxypyr-MHE is not acutely toxic to the honeybee, the "Honey Bee Toxicity of Residues on Foliage" study (GLN 850.3030) should not be needed. EFED recommends that the status of this guideline be changed from "Reserved pending outcome of tier 1 studies" to "Not required."


Comment #9 (page 6-7)
EPA has requested a new compost study due to some apparent shortcomings cited by EPA EFED during a cursory review of a study previously submitted by Dow AgroSciences ("Herbicide content changes in bench-scale compost made with fluroxypyr and dicamba treated grass clippings", MRID 45833601).  The EFED response was dated September 3, 2003 (DP Barcode D293064, PC Code: 128959).  In the review the EPA EFED scientist indicate that "The submitted study was conducted at 60°C continuously, which may have underestimated the persistence of the chemical and therefore the risk to non-target plants from contaminated compost."  However, this assertion is clearly not the case in that the study was a "self-heating study" which relied on natural temperature fluctuations as a result of the composting process...
  
In contrast to some other members of the pyridine class of herbicides, after many years of use there have been no adverse effects reported for damage to plants resulting from fluroxypyr in compost.  There are several reasons for this, in particular  due to use patterns,  lower potency of fluroxypyr relative to other pyridine herbicides,  and  a higher degradation rate in compost (ie, much less persistent) due to differences in physical chemistry.

EFED Response #9:
Additional data are needed to address the deficiencies noted in the problem formulation for fluroxypyr-MHE and fluroxypyr acid compost study (MRID 45833601) previously submitted to the Agency; otherwise a new study is needed. The deficiencies were identified based on a recent review of the study and not on the cursory review dated September 3, 2003. As noted in the problem formulation the study deficiencies include: 1) no methods (including an independent lab validation) or control spike analysis were provided to support the analytical procedures used in the study, 2) recoveries were variable, 3) dilution due to sample withdrawal and consolidation of multiple samples was not adequately described, and 4) a comparison of the composting method with typical composting practices was not provided.  

While after many years of use there have been no adverse effects reported for damage to plants resulting from fluroxypyr residues in compost, it is unclear if compost samples have been analyzed for fluroxypyr residues. Also, EPA is unaware of an analytical method for detecting fluroxypyr residues in compost. Thus, the presence or absence of the residues cannot be determined. If methods were available, these methods would need to be at or below levels of toxicological concern (0.00083 lb a.e./A) in order to rule out the potential effect of fluroxypyr residues in compost.

Currently, there are no environmental chemistry methods sensitive enough to detect fluroxypyr-MHE or fluroxypyr acid at levels of toxicological concern (0.00083 lb a.e./A). The lowest detection limit reported for fluroxypyr acid in soil is 3 ug/kg (0.007 a.e. lb/A). An independent laboratory validation has also not been submitted for the environmental chemistry method in water.
