MEMORANDUM

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

DP Barcode: 38 1731

PC Code: 10670 1

DATE: October 5. 2010

SUBJECT: EFED Response to Comments on Preliminary Problem Formulation for

Registration Review of Fosamine Ammonium

FROM: DonnaR. Judkins. Ph.D., Biologist

Environmenta l Risk Branch II

Environmental Fate and Effect Division

Office of Pesticide Programs

TlIRU:

TO :

Dana Spatz, Chief

Environmental Risk Branch III

Environmental Fate and Effect Division

Russe ll Wasem, CRM

Risk Management and Implementation Branch 1

Pesticide Re-evaluation Division (750 8P)

This memo communicates the response of the Environmental Fate and Effects Division (EFED)

to comments received on the Preliminary Problem Formulation tor the Registration Review of

Fosaminc Ammoni um (PC Code 106701). Specifically, this memorandum addresses one

comment from the Physicians Committee for Responsible Medicine (PCRM) dated August 12,

2010 and several comments from DuPont dated August 19, 2010.

PC RM Co mment:

"The Summary Document indicates that the Age ncy may request testing for avian acute oral

toxicity. We strongly support the use ofthe newly revised OEC D test guideline for the acute

avia n oral toxicity, which has been adopted by the DECO. The new approach cou ld reduce the

total number of animals by up to approximately 90%. The approach provides three testing

options: (I) limit dose test, (2) LD50-slope test, and (3) LD50 only test. The test method

selected will depend on whether or not a definitive median dose (LD50) and slope ofthe doseresponse curve are both needed. ... We hope the Agency will use the DECO 's draft test

guideline to minimi ze the number of animals used while still accounting for the safety of wild

birds: '
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EFED Response: 

The Agency requires a toxicity test be conducted to estimate the acute oral LD50 of Fosamine 

Ammonium to a passerine species. PCRM recommends that the new OECD test guideline be 

used for this test because it uses considerably fewer 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 procedure is Test Guideline (TG) 223. Current 

policy within the Office of Pesticide Programs/Environmental Fate and Effects Division 

(EFED) regarding the acceptance of avian acute 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 validation, they may then be classified as 

‘acceptable,’ assuming that they meet all other guideline requirements. 

To date the OECD has adopted the TG 223 guideline and has issued a validation report. At 

this time EFED is actively evaluating the results of the OECD validation report to determine 

if the TG 223 effects endpoints and dose/response information adequately address the 

purposes of the avian acute oral data requirement 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 protocol 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 with passerines is done. 

DuPont Comments: 

Comment on Risk to Aquatic Organisms: 

DuPont agrees with the summary of existing data for 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 rapidly degraded by microbial systems in soil further reducing the 

potential for runoff and significant persistent exposure to the aquatic environment.” 
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While there are no chronic toxicity studies with fosamine ammonium available for aquatic 

vertebrate and invertebrate species, the very low acute toxicity demonstrated on a range of taxa 

including sensitive aquatic invertebrates indicate that toxicity due to long term exposure would 

be low. The registrant suggests limiting chronic testing to Daphnia magna, but would take under 

consideration an early life stage study on rainbow trout if requested 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 problem formulation show that fosamine ammonium 

is more toxic to fish (rainbow trout LC50 = 377 ug a.i./L; MRID 41607103) than to aquatic 

invertebrates (daphnid LC50 = 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), but are not usually used to extrapolate between 

invertebrates and fish. Therefore, if the upcoming 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 species 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 could be exposed. The lack 

of these data will limit the flexibility the Agency 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 be of extremely low acute toxicity to Rattus norvegicus 

in a neurotoxicity study (LD50 >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 toxicity for both Bobwhite Quail and Mallard Duck (LD50

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

for both species (LC50 >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 toxicity demonstrated in the mammalian and bird 

studies already conducted, the registrant believes that further testing 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 bird species for terrestrial, aquatic, forestry, 

and residential outdoor uses. Because passerine species 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 LD50 using bobwhite quail 

or mallard duck data may over- or under-estimate risks to passerines. If the upcoming risk 
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assessment, including listed species assessment, is performed without these data, the Agency 

would have to assume that fosamine ammonium “may affect” listed birds directly (and listed 

species from other taxa indirectly), and use of fosamine ammonium and its formulated 

products may need to be restricted in areas where listed species could be exposed. The lack 

of these data will limit the flexibility the Agency 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. Because the 

850.2100 guideline has not yet been finalized, protocols for the study of passerine species 

should be submitted to EPA for approval prior to study initiation.