MEMORA NDUM UN ITE D STATES ENV IRON ME NTAL PR OTEC T I ON AGE NCY W ASH I NGTON D .C

. , 2 0460

O FFIC E O F C H E MICAL SAFETY AN D PO LL UTION P REVENT IO N

D P Barcode : 38 1 73 1 P C C ode : 106 70 1 DAT E : O c t ober 5

. 2010

S U BJE CT : E FED Re spo n se t o C o mm ents on Pr el i minary Pr oblem F ormulation f o r Re gistration Review of Fosamine Ammon ium

F ROM : 

### Donna R. J udkin s. P h

. D., B iol o g is t Environme n ta l Ri s k B ranch II En v ironme n ta l Fat e and E ffect D iv i s io n Office of Pe s tic ide Program s

Tl IR U :

TO : D ana Sp at z, C h ief E nvironmental R i s k Bran ch III E n v i ro nm e nt a l Fa t e an d Effec t D ivi s ion

R u sse ll W asem , C RM Ri s k Ma nagement and I mple ment at i o n B ranch 1 P e st icide Re -evaluation D i vi sion (750 8P)

T hi s me m o c om munic ates t he re sp on se o f th e En v i ro n me ntal F a te a nd E ffects Di v i sio n ( EFED)
t o c o mmen t s rece i ved o n th e Preli minary Prob lem Fo rm u l a t io n t or t he Re g i st r at i o n Re v iew o f Fo sa m i nc A mmoni um (P C C ode 10 6 701 ) . S pecifically, thi s m em o r an dum a dd resse s o n e

co mmen t fro m the P h y sician s Co m m itte e for Re spon sib le Me dicine (P C RM) d at e d A ugust 1 2

, 2 0 10 an d s e ver a l co mments f ro m D u Po nt dat ed Au g u st 1 9, 2 01 0

.

P C RM Co mment:

" The Su mmary Docu me nt i ndicate s th a t t he Age ncy m ay reque s t t e stin g for av ian ac ute o ral
t oxicity

. We s tr ong l y s uppo rt th e u s e of t h e ne w ly revised OEC D t e st g ui d eline fo r t he ac u te avia n o ra l t oxicity, whi ch has been ado pted by the DE C O

. Th e ne w a pproach cou ld red uce t he
t ota l n umber o f anim a l s by u p to a p proxima tely 90 %

. Th e approa c h p rovide s t h r ee tes ting
op tion s : ( I ) l imit do se t e s t, (2) LD 50- sl ope te s t, a nd (3 ) L D50 o n ly t e st. Th e tes t m ethod selec ted will depe nd on whe t her or no t a d efinitive median d ose (LD50 ) and s lope of the d osere s pon s e curve a re both n eeded

. .. . We h ope t he Age n cy wi ll u se t he DE CO ' s draft t est guideli ne t o minimi ze t he n umber of animal s u sed whi le s ti ll a ccoun ting fo r th e safety o f wild bi rd s : '

### 2 EFED Response:

The Agency requires a toxicity test be conducted to estimate the acute oral LD 50

### of Fosamine Ammonium to a passerine species. PCRM recommends that the new OECD test guideline be used for this test because it uses considerablyfewer animals than the traditional LD50 test described by Test Guideline 850.2100. The new OECD test guideline for measuring avian acute oral toxicity with a sequential dosing pr ocedure is Test Guideline (TG) 223. Current policy within the Office of Pesticide Program s/Environmental Fate and Effects Division (EFED) regarding the acceptance of avian acu te effects studies conducted using the TG 223 protocol states the following:

Until the OECD TG 223 validation process is completed and the guideline has been approved by OECD, studies that utilize this guideline should not be classified; pending results of the valida tion, they may then be classified as ‘acceptable,’ assuming that they meet all other guideline requirements.

To date the OECD has adopted the TG 223 guide line and has issued a validation report. At this time EFED is actively evaluating the resu lts of the OECD validation report to determine if the TG 223 effects endpoints and dose/res ponse information adequately address the purposes of the avian acute oral data requireme nt as described in 40 CFR Part 158. Until the Agency’s evaluation of that validation report is completed, EFED will not classify avian toxicity studies performed using the TG223 protoc ol and the studies cannot be used to fulfill data requirements. Therefore, we cannot say at this time whether or not avian toxicity studies done under TG 223 will be acceptable to meet our data requirements.

Validation work conducted on TG 223 test guideline to date has been limited to studies with upland game birds (e.g., northern bobwhite). Because no work has been done to date to validate this guideline for passerine species, it is doubtful that we would accept studies done under this guideline for fulfilling requirements for passerine acute toxicity data unless additional validation work w ith passerines is done.

DuPont Comments:

Comment on Risk to Aquatic Organisms:

DuPont agrees with the summary of existing datafor acute toxicity of fosamine ammonium to aquatic organisms, showing low levels of toxicity to aquatic animals and little bioaccumulation in aquatic organisms. DuPont also points out that testing with green algae and duckweed show that fosamine ammonium also has low toxicity to aquatic plants. “While a 40% effect level was observed at 22 ppm, the compound poses a minimal likelihood of long-term effects to aquatic non-vascular and vascular plants since there are no repeated applications of fosamine ammonium per year and it is not applied directly to aquatic water bodies. Although the compound is mobile and highly soluble, it is rapidl y degraded by microbial systems in soil further reducing the potential for runoff and significant persistent exposure to the aquatic environment.”

### 3 While there are no chronic toxicity studies w ith fosamine ammonium available for aquatic vertebrate and invertebrate species, the very lo w acute toxicity demonstr ated on a range of taxa including sensitive aquatic inverteb rates indicate that toxicity due to long term exposure would be low. The registrant suggest s limiting chronic testing to Daphnia magna, but would take under consideration an early life stag e study on rainbow trout if reque sted to do so by the EPA.”

EFED Response:

40 CFR Part 158.630 requires both Guideline 850 .1300 (aquatic invertebrate life cycle) and 850.1400 (fish early-life stage) studies for all terrestrial, forestry and residential uses. Available toxicity data presented in the probl em formulation show that fosamine ammonium is more toxic to fish (rainbow trout LC 50

### = 377 ug a.i./L; MRID 41607103) than to aquatic invertebrates (daphnid LC 50

### = 1524 ug a.i./L; MRIDs 00143492 and 92086005). Acute to chronic ratios are sometimes used to estimate chronic toxicity when taxa are very similar (e.g., freshwater shrimp to saltwater shrimp), butare not usually used to extrapolate between invertebrates and fish. Therefore, if the upc oming risk assessment, including listed species assessment, is performed without these data, the Agency would have to assume that fosamine ammonium “may affect” listed fish directly (and listed spec ies from other taxa indirectly) based on chronic exposure, and use of fosamine ammonium and its formulated products may need to be restricted in areas where listed species coul d be exposed. The lack of these data will limit the flexibility the Agen cy and registrants have in complying with the Endangered Species Act and could result in restrictions for fosamine ammonium use that might prove to be unnecessary given data to address this area of uncertainty.

Comment on Risk to Terrestrial Organisms:

Fosamine ammonium has been shown to beof extremely low acute toxicity to Rattus norvegicus in a neurotoxicity study (LD 50

### >1954 mg ai/kg bw/day). Chronic studies with R. norvegicus indicated low chronic toxicity (NOAEC = 200 mg/kg/d, and an LOAEC = 1000 mg/kg/d). Avian testing indicates low acute oral toxicityfor both Bobwhite Quail and Mallard Duck (LD 50 

### >5000 mg/kg bw/d for both species). Toxicity from dietary exposure was also extremely low for both species (LC 50

### >5620 ppm diet). Reproduction studies on the Mallard Duck resulted in a NOAEC of 11,600 mg/kg/d.

Based on the very low acute and chronic toxici ty demonstrated in the mammalian and bird studies already conducted, the registrant believes that further te sting on a passerine species is unwarranted.

EFED Response:

Avian Acute Oral Toxicity Test(850.2100) data are required for one passerine species and either one waterfowl species or one upland game bi rd species for terrestrial, aquatic, forestry, and residential outdoor uses. Because passerinespecies have higher metabolic rates due to their smaller sizes than either waterfowl or upland game bird species and because they may utilize different metabolic pathways, they may be more or less sensitive to fosamine ammonium. The current method of calculating a weight-adjusted LD 50

### using bobwhite quail or mallard duck data may over- or under-estimate risks to passerines. If the upcoming risk

### 4 assessment, including listed species assessment, is performed without these data, the Agency would have to assume that fosamine ammonium “may affect” listed bird s directly (and listed species from other taxa indire ctly), and use of fosamine ammonium and its formulated products may need to be restricted in areas where listed species coul d be exposed. The lack of these data will limit the flexibility the Agen cy and registrants have in complying with the Endangered Species Act and could result in restrictions for fosamine ammonium use that might prove to be unnecessary given data to a ddress this area of uncertainty. Because the 850.2100 guideline has not yet been finalized, pr otocols for the study of passerine species should be submitted to EPA for approval prior to study initiation.