OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

April 9

, 201 5

PC Code s : 122805 & 1 22809

MEMORANDUM DP Barcode: D 42577 2

SUBJECT : EFED Response to Registrant Comments Regarding the Registration Review Problem

Formulation for F l uazi fop

- p

- butyl

FROM : N.E. Federoff, Wildlife Biologist

Environmental Risk Branch 2

Environmental Fate and Effects Division ( 7507P)

THRU : Brian Anderson, Chief

Environmental Risk Branch 2

Environmental Fate and Effects Division (7507P )

T O : Matthew Manupella, CRM

Pesticide Re

- Evaluation Division (7508P)

The Environmental Fate and Effects Division (EFED) has completed the responses to the

Registrant (Syngenta Crop Corporation LLC ) comments regarding the preliminary problem

formulation of f luazifop

- p

- butyl

.

E P A sta t eme n t

R e f e r e n ce ( P a g e 3

, B u ll et 2) N o da t a ha v e been su b m i tt ed r e g a r d i n g c h r o ni c t o x i c i t y t o

estua r i n e/ m a r i ne f i sh or i n v er t e b r ate s

. S y n g e n t a C o m m e nt : S y n g e n t a p r e v i o u s l y su b m it t ed a chron i c m y s i d s t ud y on t he p a r e n t

compou n d ( M R I D 0 0 0 9 3 8 0 5 )

. S y n g e n t a r es p e c tf u l l y w i l l pro v i de a co u rt e sy co p y of t he or i g i n a l

s t u d y r e p o r t i n a sep a r a t e sub m i ss i o n

.

EPA Response : EFED agrees this study was submitted (MRID 00093805 )

. The study was do n e

using Fluazifop

- butyl (122805)

. It was listed as supplemental and non

- repairable. The NOAEC

for this study would be 15 ppb. This study need s to be repeated using fluazifop

- p

- butyl

(122809)

.

E P A sta t eme n t

P a g e 1 4

, T a bl e 1,

F l u a z i f op

- p

- ac i d H e n r y ’ s L a w C o n s t a n t

S y n g e n t a C o m m e nt : S y n g e n t a w il l r es p ec t f u ll y su b m i t a d d i t i o n al d a t a f o r t h i s d a t a g ap by t he

e n d o f 1 st Q u a r t er 2 0 1 5

.

EPA Response: EFED will review the data once submitted.E P A sta t eme n t

R e f e r e n ce ( P a g e 2 9,

P aragraph 5 ) A n A C R v a l ue w as ob t a i n e d fr om t he fr es h w ater a ni m al s t u di es a n d

a p p li ed t o t h e ac u t e t o x i c i t y d a t a f or estu a r i n e/ m a r i ne sp e c i es t o

estim a t e c h r o ni c t o x i c i t y v a l u e s f o r t h e se sp e c i es. T h i s a p pro a ch

y i e l d e d a N O AE C v a l ue o f 3

. 10 m g a i / L f or t he e s t u a r i n e/ m a r i ne f i sh

C

. v a r i e g atu s

. S y n g e n t a C o m m e nt : S y n g e n t a a grees t h a t an AC R i s a us e f ul t ec h n i q u e f o r ca l cu l ati n g

chron i c e ff e c t s v a l u e s f or m a r i ne f i s h

.

EPA Response: EFED would rather use actual test data, but if none are available, EFED

agrees that ACR values can be used.

E P A sta t eme n t

R e f e r e n ce ( P a g e 3 0,

P aragraph 1 , L i ne 4) F l u a z i f op

- p

- b u t y l i s s li g h t l y t o x i c t o t he h o n e y b e e wi t h an ac u t e

co n t act L D 50 o f 63 μ g/ b ee

S y n g e n t a C o m m e nt : S y n g e n t a n o t es t h a t t he a c ute co n t a c t t o x i c i t y s t u d y ( M R I D 0 0 1 6 2 4 5 3 )

c i t ed i n t he P r e li m i n a r y P r o bl em F o rm u l a t i on ( P P F) r e su l t ed i n L D 50 > 2 0 0 μ g / b e e

, i n di cati n g t h a t f l u a z i f o p

- P

- b u t y l i s prac t i ca ll y n o n

- t o x i c t o h o n e y b e es.

EPA Response: The DER in question (252825) was an acceptable study resulting in oral

LD50s of > 200 ug/bee for technical grade and 63 ug/bee for formulation. Results for acute

contact were LD50s of >200 ug/bee for technical grade and >100 ug/bee for formulation. The

most toxic value was listed but should have said for oral and not contact.

E P A s ta t eme n t

R e f e r e n ce ( P a g e 3 1,

T a bl e 9 ) R e f e r e n ced e n d p o i nt f or a q u a t i c non

- v asc ul ar s t u d i es i s prese n t ed a s

b i omas s

. S y n g e n t a C o m m e nt : S y n g e n t a r es p e c t f u ll y s t at e s t h a t e ff e c t i v e conce nt r a t i o n s ( EC x )

ca l cu l ated b a sed o n gr o w t h r ate a r e co n s i d e r ed m ore r o b u s t t h a n t h o se b as e d on s t a n d i n g c r op

( ce l l d e ns i t y a n d b i om as s) f or a g i v en t i m e

- p oi nt s i nce g r o w t h r a t e is i n d e p e n d e nt o f e x p o sure

t i m e ( EP A 2 0 1 2 ) . F o r a q u at i c p l a n t s

, s t u d y d u r a t i o n

, co n d i t i o n s o f t e m p e r atu r e

, li g h t , a n d

n u tr i e n t s

, a n d r e p o r t ed e n d p oi nts can v ary co n s i d e r a bl y amo n g s t u di es. Ot h e r r es o urce li m i t i n g

f

act o r s, such as n ut r i e n t d e p l eti o n and se l f

- sh a d i n g, can c o m p li cate t he i n t erp r e t ati o n o f

r e p o r t ed p l a n t EC x s. T h e se f a c t o r s m ay a ff ect s t u dy r es ul t s, w h i ch cou l d r es ul t i n b i as e d

estim a t es in ce r t a i n cas e s f o r s o m e sp e c i es ( EPA 2 0 1 2 )

. U s i ng a b so l ute b i omass can p o t e n t i a ll y

r es ul t i n p a r t i cu l arly m i s l e a d i ng EC x ’ s w h e n g r o w t h r ates are m o d es t

, a n d a d e p a r t ure fr om

e x p o n e nti a l g r o w t h w il l b e m o s t p r o n o u nc e d i n t h e t r e at m e n t s w i t h t he h i g h est gro w t h

r a t es ( EP A 2 0 1 2 )

. W i t h r es p e c t t o t o x i c i t y t esti n g, d i ff e r e n ces in d e s i g n o f t he s t u d y can

r es ul t i n comp li cated gro w t h d y n a m i cs a n d r e l ati o ns hi ps t h at a r e d i f f

i cu l t t o i n t erp r et a n d

app l y ( EP A

2 0 1 2 )

.

A s i n di cated by B e r gto l d a n d D o hmen ( 2 0 1 1 )

, t he O r g a ni z ati o n f o r E co n o m i c C o o p e r ati o n and

D e v e l o p m e n t ( O ECD ) i n d i cates a c l e a r p r e f e r e n c e f o r gro w t h r ate as t he a p p r o p r i ate e n d p o i nt

i n t he l emna a n d a l g al t o x ic i t y t est g u i d eli ne (O EC D 2 0 0 6 a,b )

. S p e c i f i ca ll y

, t h e O EC D

g u i d eli ne f o r t esti n g gro w t h i n h i b i t i on i n fr es h w ater a l g a and c y a n o b acte r i a ( O EC D 2 0 0 6 a )

s t ate s :

Page 2 of 6“ EC x v a l u e s b a sed u p on a v era g e sp e c i f i c g r o w t h r ate ( E r C x ) w il l g e n era ll y be

h i g h e r t h a n r es u l t s b a s e d upon y i e l d ( E y C x ) i f t h e t e s t c o n di t i o n s o f t h i s

G u i d eli ne are a d h e r ed t o, d u e t o t h e m a t h e m a t i cal b a s i s o f t he r es p e c t i v e

approach e s. T h i s sh o u l d not b e i n t e rpr e t ed as a d i ff erence i n sens i t i v i t y b e t w e e n

t he t w o r e s p o nse v ari a b l es, s i m p l y t h a t t he v a l u e s are d i ff ere n t m a t h e m atic all y

. T he co n ce p t o f a v era g e sp e c i f i c gro w t h r ate i s b a sed on t he g e n e r al e x p o n e nti a l

gro w t h p at t e r n o f a l g ae i n n on

- li m i t ed c u l t ures, w h e r e t o x i c i t y i s estim a t ed on

t he b a s i s o f t he e f f

e c t s o n t he gro w t h r a t e, w i t h o ut b ei n g d e p e n d e n t on t he

a b so l ute l e v el o f t he sp e c i f i c g r o w t h r ate o f t h e con t r o l , s l o p e o f t he

c o nc e nt r a t i o n

- r e sp o nse c u rv e or on t e s t d u r ati o n

. I n co n t r ast, r es u l t s b a s e d upon

t he y i e l d r es p o n se v ari a b l e a r e dependent upon all t he s e o t h e r v a r iab l es. [ Y i eld]

is d e p e n d e n t on t he sp e c i f i c g r o w t h r ate o f t he a l g al s p e c i es used in e a ch t est

a n d on t he m a x i m um s p ec i f i c g r o w t h r ate t h a t can v ary b e t w e e n spec i es and

e v en d i f f

e r e n t a l g al s t r a i ns. T h i s r es p o n se v ari a b l e shou l d n o t be us e d f o r

comp a r i ng t he se n s i t i v i t y t o t o x i ca n t s amo n g a l g al sp e c i es or e v en d i f f

e r e n t

s tr a i n s

. ”

B as e d on t he a f or e m e n t i o n ed i n f o r m ati o n

, r e l ati v e g r o w t h r a t e is t he m ost a p pro p r i ate

a q u a t i c p l a n t e n d p o i nt f o r ec ol o g i cal r i sk ass e s s m e n t

.

B erg t o l d, M

. a n d G. P

. D o h m e n . 2 0 1 1

. Bi omass o r g r o w t h r a t e e n d p o i nt f o r

a l g ae a n d a q u a t i c p l a n t s: R e l e v a n ce f o r t he a q u a t i c r i s k ass e s s m e n t o f

h e r b i c i d e s. I nt e gr. E n v i r o n

. A sses s

. M a n a g

. 7 : 2 3 7

- 2 4 7.

O EC D ( O r g a ni z ati o n f o r E co n omic C o o p er a t i on a nd D e v e l o p m e n t) . 2 0 0 6 a

. O EC D G u i d eli ne 2 0 1: F r es h w ater a l g a a n d c y a n o b acte r i a, g r o w t h i n h i b i t i on

t e s t

. A d o pted 23 M arch 2 0 0 6

. P aris.

O EC D ( O r g a ni z ati o n f o r E co n omic C o o p er a t i on a nd D e v e l o p m e n t) . 2 0 0 6 b

. O EC D G u i d eli ne 2 2 1: L e m na s p . gro w t h i n h i b i t i on t e s t

. A d o pted 23 M arch

2 0 0 6

. P aris.

U S EPA

, 2 0 1 2

. P r o p os e d M ethod ol o g y f or S p e c i f y i ng A tr a z i ne L e v e l s o f

C o n cern f or P r ot e c t i on o f Pl a n t C om m u ni t i es i n F r e sh w ater E cos y s t e m s. R e p o r t

T o : E n v i r o n m e n t al F a t e a n d E ff e c t s Di v i s i o n

, O ff i ce o f P estic i de P r o gr a m s,

U.S

. E n v i r o n m e n t al P r ot e c t i o n A g e n c y

, W a sh i n gton, DC

. EPA / 6 0 0/ R

- 12 / 0 1 9

. M i d

- C o n t i n e nt E co l o g y Di v i s i o n

, N ati o n a l H e al th a n d E co l o g i cal E ff ects

L a b o r ato r y

, O f f

i ce o f R es e a r ch and D e v e l o p m e n t

, U

. S

. E n v i r o n m e n t al

P r ote c t i on A g e nc y

, D u l uth, M N

. M arch 5, 2 0 1 2

.

EPA Response : EFED ’s current approach is to use the most sensitive endpoint available to

assess risk to terrestrial and aquatic organisms. For plants, both biomass as well as growth are

possible endpoint parameters.

E P A sta t eme n t

R e f e r e n ce ( P a g e 3 1,

T a bl e 1 0 ) S ub

- ac u t e d i eta r y L C 50

= 4 1 4 1

. 5 p p m

, ( M R I D 0 0 0 8 7 4 8 1, 1 9 87

S y n g e n t a C o m m e nt : S y n g e n t a r es p e c t f u ll y su b m i t s t h a t t he e n d p o i nt f or M R I D 0 0 0 8 7 4 81 i s >

2 1 3 4 8 ppm ae ( 2 5 0 0 0 p pm a i ) r a t h e r t h a n t he c it ed 4 1 4 1

. 5 p p m a e

.

Page 3 of 6EPA Response : This study (MRID 00087481, 1980) is supplemental and did not meet

guideline requirements. The ducks rejected food at all dose levels for the first 2 days of the

study and at all doses but the lowest two treatment levels for the remainder of the test. The

25

, 000 ppm ai endpoint was from the 1980 supplemental study with Fluazifop b utyl. The

cited data were for Fluazifop

- p

- butyl (MRID 41199201, 1987), although the LC50 endpoint

should have been listed as being >4850 ppm ai)

.

E P A sta t eme n t

R e f e r e n ce ( P a g e 3 2,

T a bl e 1 0 ) I ns e c t s, h o n e y b e e acu t e co n t ac t , 48 h r L D 5 0 =63 μg/b e e ( M R I D

00162453)

S y n g e n t a C o m m e nt : S y n g e n t a su b m i t s t h a t t he 48 hr co n t a c t L D 50 f o r M R I D 00162453 i s

> 2 0 0 μ g f l u a z i f op

- P

- b ut y l / b e e.

EPA Response : As mentioned previously, the LD50 of 63 ug/bee was the most toxic value

but was for the toxicity of the oral exposure study . The acute contact LD50 was >200 ug/bee

for the technical grade

.

E P A S t atement

P a g e 35 8. E n d a n g e r ed S p e c i es A ssessme n t

S y n g e n t a C o m m e n t : A su m m ary o f t he t y p e s o f h i g h e r

- t i er d a t a a n d as s essme n t r e f i n e m e n t s

a v a i l a bl e t o m o r e a ccur a t e l y a n d r e ali s t i ca ll y e v a l u a t e p o t e n t i al r i sks t o e n d a n g e r ed sp e c i es i s

pro v i d e d in M R I D 4 9 2 0 0 6 0 1

.

EPA Response : EFE D will take this data into consideration under any future endangered

species assessments.

E P A sta t eme n t

R e f e r e n ce ( P a g e 4 5,

T a bl e 1 6 ) H o n e y b e e acu t e adu l t o r al d a t a is n e e d ed f or r i s k ass e s s m e n t

S y n g e n t a C o m m e nt : S y n g e n t a n o t es t h a t M R I D 0 0 1 6 2 4 53 p r o v i d e d adu l t ac u t e o r al d a t a. T he

48

- hr oral L D 50 w as > 2 00 μ g f l u a z i f o p

- P

- b u t y l / b e e

. S y n g e n t a r es p e c t f u ll y propos e s t h a t

M R I D 00162453 w i l l sati s f y t he h o n e y b e e adu l t ac u t e o r al d a t a r e q u i r e m e n t

.

EPA Response : EFED agrees this data has been submitted

. This study is adequate for a limit

test and no new adult oral bee data are required

.

E P A sta t eme n t

R e f e r e n ce ( p a g e 4 6 ) A v i an R e p r o d ucti o n ( 8 5 0

. 2 3 0 0 )

E s t u a r i n e / M ari n e F i sh a n d I n v er t e b r ates ( 8 5 0.15 0

. a n d 8 5 0.140 0 )

A q u a t i c Pl a n t T o x i c i t y ( 8 5 0

. 4 4 0 0 , 8 5 0.4500 & 8 5 0.455 0 )

S y n g e n t a C o m m e nt : T h e a v a il a bl e da t a f or f l u a z i f o p

- P

- b u t y l a n d o t h e r h erb i c i d e s i n t he

same c l ass d e m o n s t r ate t h a t t he ac i d d e gradate f or t h i s c l ass o f compo un d is m uch l ess

b i o l o g i ca ll y acti v e t h a n t h e pa r e n t c o m p o u n d

. S y n g e n t a p l a n s t o su b m i t ( i n a se p a r ate

su b m i ss i o n ) a d d i t i o n al t o x i c i t y d a t a f o r p a r e n t a n d t he ac i d d e g r a d at e

.

EPA Response : EFED will review these data upon submission.

Page 4 of 6E P A sta t eme n t

R e f e r e n ce ( A p p e n d i x

B : E co l o g i cal

T o x i c i t y D ata, P a g e

6 5

, A q u a t i c

I n v er t e b r a t e D a t a) ( 1) W a t er f l ea ( D a p h ni a m a g n a )

, M R I D 0 0 0 8 7 4 9 0 ( 48 hr EC 5 0 =240.1

p p m a e / 2 8 1.2 p p m a i ) a n d M R I D 0 0 1 6 2 4 52 ( 48 hr L C 5 0 s=47 3

. 0 p p m

a e / 5 5 3.9 p p m a i , 4 6 5.9 p pm a e / 5 4 5.6 p p m a i , a n d 3 5 2.2 p p m

a e / 4 1 2.4 p p m ai f or d i f f

e r e n t R : S r ati o s

. ( 2) M y s i d, 28 D L C 5 0 =6 6

. 35 p p b ae ( 7 7

. 7 p p b a i )

, M R I D 0 0 0 9 3 8 0 5

, 1981

S y n g e n t a C o m m e nt : ( 1 ) S y n g e n t a r es p e c t f u ll y n o t es t h a t M R I D 0 0 0 8 7 4 90 and M R I D

00162452 us e d t he a c i d d e gradate r a t h e r t h a n t h e pa r e n t c o m p o u n d

. A s b o t h s t u di es t ested t he

t o x i c i t y of t he ac i d d e g r a d a t e, a con v ersi o n t o a c i d e q u i v a l e n t co n ce nt r ati o n is not n e e d ed a n d

t he e n d p o i n t s sh o u l d be 5 5 3.9 p p m , 5 4 5.6 p p m

, a nd 4 1 2.4 p p m r a t h e r t h a n 473.0 p p m a e

, 4 6 5.9 p p m a e

, a n d 3 5 2

. 2 p p m ae b a s e d on t he a c i d conce nt r ati o n. B o t h M R I D 0 0 0 8 7 4 90 a n d

M R I D 0 0 1 6 2 4 52 d e m o n s tr a t e t h a t t he ac i d d e gra d ate h a s l ess b i o l o g i cal a c t i v i t y t o

a q u a t i c i n v er t e b r ates t h a n t he p a r e nt

. ( 2) T h e m y s i d 28 d N O A E C o f M R I D 0 0 0 9 3 8 05 i s 0.041 p p m ae ( 0

. 0 4 8 p p m a i )

.

EPA Response : 1. MRID 162451 used fluazifop

- butyl as well as two EC formulations. This

study was classified as unacceptable and can’t be used for risk assessment . MRID 162452 was

deemed as supplemental with 48 hr EC50s of 553.9 mg/L for R:S 1:1, 467.1 mg/L for R:S 7:1

and 412.4 mg/L for R:S 14:1 mixtures resulting in a classification of practically non

- toxic

. 2.

Th is study was done using Fluazifop

- butyl (122805) . It was listed as supplement al and non

repairable. The NOAEC for this study would be 15 ppb. This study need s to be repeated using

Fluazifop

- p

- butyl (122809)

.

E P A sta t eme n t

R e f e r e n ce ( P a g e 6 6,

F i sh D a t a) ( 1) R a i n b ow tr o u t , 6.2 g, s t ati c

, / F l u a z i f o p

- b u t y l

, 9 8% a i , L C 50

9 9

. 9 0 9 p p m ae ( 1 1 7 p p m a i )

, M R I D 0 0 0 8 7 4 8 3 , 1 9 81

( 2) F athead m i n n o w

, e a r l y l i f e

, f l ow

- t h r o u g h, / F l u a z i f o p

- b u t y l

, 9 0

. 2 %

, 30 D L O E C 0.203 p p m a e ( 0

. 2 3 8 p p m a i )

, M R I D 0 0 0 9 3 8 0 8

, 1 9 81

S y n g e n t a C o m m e nt : ( 1 ) T he 96 h r L C 50 f o r M R I D 0 0 0 8 7 4 83 i s 1

. 37 m g / L a i

. T he M R I D f or

t h i s r a i n b ow tr o u t s t u d y i s 0 0 0 8 7 4 8 7 , 1 9 8 1

. A s M R I D 0 0 0 8 7 4 87 t e s t ed t he t o x i c i t y of t he ac i d

d e gradat e

, a co n v ersi o n t o ac i d e q u i v a l e n t co n c e nt r a t i on i s n o t n e e d ed a n d t he e n d p o i nt sh o u l d

be 117 p p m r ath e r t h a n 9 9

. 9 p p m b a s ed on t he a c i d conce nt r ati o n. S y n g e nta r es p ec t f u ll y

su b m i t s t h a t t h i s s t u d y c o n f i rm s t he l ow b i o l o g i cal acti v i t y of t he ac i d d e g r a d ate t o f i sh.

( 2) T hi s a p p e a r s t o be a t yp o g r a p h i c e r r o r

. T he f a t h e ad m i n n ow 3 0

- d NO E C i s 0

. 2 0 3 p p m ae ( 0.238 p p m a i )

, r a t h e r t h an t he LOE C

.

EPA Response : 1. EFED notes that the LC50 endpoint for the acid study is 117 ppm. This study

was cited in the DER as Hill et al., 1981. 2. The acceptable 1981 study (MRID 93808) resulted

in a 30 day NOAEL of 0.103 ppm , the highest test level with results visibly simil ar to the

controls

. This value was to be used until new data were submitted. Th e 1991 study (419006

- 02)

was invalid because measured concentrations were inconsistent.

E P A sta t eme n t

R e f e r e n ce ( p a g e 6 7

, A v i an D ata) ( 1) Al l n o n

- d e f i n i t i v e end p o i nts are r e p o rt ed as l ess t h a n v a l u e s ( “ < ” )

. ( 2) M a ll ard d u c k , 9 D

, d i eta r y

, / F l u a z i f o p

- P

- b u t y l , 9 5 % a i

, M R I D

00087481, 1 9 8 7

. 8 D L C 50 4 1 4 1

. 5 p p m ae ( >48 5 0 ppm a i )

S y n g e n t a C o m m e nt : ( 1 ) S y n g e n t a r es p e c t f u ll y su b m i t s t h a t a l l e n d p o i nts sh o u l d be

Page 5 of 6r e p o r t ed as g r e a t er t h a n v a l u e s (“ > ” )

. ( 2 ) T he e n d p oi nt f o r M R I D 0 0 0 8 7 4 8 1 is i d e n t i f i ed a s a

L C 50 v a l ue of > 2 1 3 4 8 p pm ae ( 2 5 0 0 0 p p m a i ) r a t h e r t h a n t he c i t ed 4 1 4 1. 5 ppm a e

.

EPA Response : 1. EFED agrees, values should be > and not <. 2. This study (MRID

00087481, 1980) is supplemental and did not meet guideline requirements. The ducks rejected

food at all dose levels for the first 2 days of the study and at all doses but the lowest two

treatment levels for the remainder of the test. The 25000 ppm ai endpoint was from the 1980

supplemental study with Fluazifop butyl. The cited data were for Fluazifop

- p

- butyl (MRID

41199201, 1987), although the endpoint should have been >4850 ppm ai).

Page 6 of 6