OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION **UNITED	STATES	ENVIRONMENTAL	PROTECTION	AGENCY**

**WASHINGTON	D.C.,	20460**

DP	Barcode:		D 42468 6 PC	Code: 128968 Date: February 1 9 , 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 Probl em	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	lik e	to	obtain	this	independent	laboratory	validation	of	the	analytical	method	for measuring	fluroxypyr - MHE	in	water.

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**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	Unpublished	report.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 , w as	inadvertently	excluded	from	the review of	ecotoxicity	data	in	the problem	formulation	document . An	EFED	review	of	this	study	has identified numerous serious	deficiencies: 1. The	number	of replicates	per	treatment	level	(3)	is	less	than	recommended	(4). 2. The	dilution	water	characteristics	were	not	reported. 3. Cell	growth	in	the	solvent	control	was	significantly	greater	than	in	the	negative	control, indicating	that	the	solvent	(DMF)	enhanced	gr owth	of	the	diatoms. 4. 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. 5. 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	tran sformation	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. 6. 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	a s	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

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plants	at	different	growth	stag es;	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 report ed 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.	Eurofin s	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	LD 50 value	is	>	100	μg/bee	indicating	low	toxicity	to adult	honeybees.	“Cole,	J	(1983).		The	acute	contact	and	ora l	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	prot ocol,	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	guidel ine	and	laboratories	experienced	in	conducting	th ese 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

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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	avail able	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. 1 Several	testing	laboratories	also	have	experience	with cond ucting	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	initiat ed. **Comment	# 8**  **(page	6):** There	is	low	toxicity	of	fluroxypyr- meptyl	to	adult	honeybees	observed	in	the	acute	contact	studies (100	μg/bee	and	>25	μg/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	show ing 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 nee ded . 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	D2 93064,	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	contaminate d	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	oth er	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 fluroxypy r - 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)

1 http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.pdf

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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	unclea r	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	fluro xypyr 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	μg/kg	(0.007	a.e.	lb/A).	An	independent	laboratory validation	has	also	not	been	submitted	for	the	envi ronmental	chemistry	method	in	water.