.

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460'

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

September 30, 2010

SUBJECT: Fosamine Ammonium: Response to Comments on the Human Health Risk

Seoping Document in Support of Registrat ion Review

PC Code: 106701 DP Barcode: 0381730

Decision No.: 439219 Registration No.: NA

Petition No.: None Regulatory Action: Registration Review

Assessment Type: Response to Comment Reregistration Case No.: NA

TXR No.: None CAS No.: 25954-13-6

MRID No.: None 40 CFR:

FROM: Becky Daiss, Biologist ;:£~ Risk Assessment Branch 4 J

Health Effects Division (7509P)

Office of Pesticide Programs

OUG~.Susan Hummel, Senior SCient Risk Assessment Branch 4 0

Health Effects Division (7509P)

Office of Pesticide Programs

TO: Eric Miederhoff

Risk Manager Reviewer

Reregistration Branch 3

Pesticide Reevaluation Division (7508P)

Office of Pesticide Programs

Attached is Health Effects Division's (HED) response to comments submitted on the human

health risk assessment status update for fosamine ammonium conducted as part ofthe

Registration Review process (0365773, 12/2/09) . A summary ofsubmitted comments followed

by HED's response is provided below.

Page 1 of3
Page 2 of 3 

Comment: The toxicity categories reported in the scoping document for acute dermal, acute 

inhalation, and acute eye irritation are incorrect. DuPont submitted new acute dermal, inhalation 

and irritation toxicity studies subsequent to publication of the Reregistration Eligibility Decision 

document (RED) in January, 1995. These studies, which were reviewed and determined to be 

acceptable by EPA, support revised classifications of Category IV for Acute Dermal and 

Inhalation Toxicity and Category III for Acute Eye Irritation. 

HED Response: DuPont is correct. Revised acute toxicity category designations for these 

exposure routes based on the studies cited by DuPont will be included in the registration review 

assessment conducted for fosamine ammonium. 

Comment: EPA commented on the acute neurotoxicity study in rats (MRID 42946501) saying, 

“rats showed clinical signs of toxicity (diarrhea) at the low dose and possible neurotoxic effects 

(slight palpebral closure and irregular respiration) at higher doses”. The finding of diarrhea in 

one animal in the low dose group should be reviewed as incidental. Diarrhea was also found in 

the baseline animals (pre-treatment) at the same incidence. Regarding palpebral closure and 

irregular respiration, they do not indicate neurotoxicity in the absence of other function 

observational battery changes. These findings are more consistent with stress from compound 

related systemic toxicity and not neurotoxicity. 

HED Response: The Human Health Risk Scoping Document in Support of Registration Review 

summarizes findings and conclusions reported in the 1994 risk assessment conducted in support 

of the Reregistration Eligibility Decision document (RED). DuPont’s comments on the 

significance and/or implications of effects observed in the acute neurotoxicity study in rats will 

be considered as part of the comprehensive assessment conducted for the registration review of 

fosamine ammonium. 

 

Comment: EPA is requesting a developmental toxicity study in a non-rodent species for this 

non-food use pesticide. DuPont requests a waiver for this rabbit developmental toxicity study 

for the following reasons: Given the labeled uses of fosamine ammonium, there will be virtually 

no chance for exposure to this compound via the oral route, the route used in developmental 

toxicity studies. Dermal absorption is expected to be very low for such a highly water soluble 

compound. Inhalation exposure is also not expected to be relevant to the doses that would be 

used in the non-rodent developmental toxicity study. Therefore, it is difficult to see how a rabbit 

developmental toxicity study by oral administration would be additive to the risk assessment. 

Additionally, the reason given for needing the developmental toxicity study in rabbits in EPA’s 

Human Health Risk Scoping Document is that it would eliminate the uncertainty of assessing 

risk in the sensitive (or insensitive) species. Fosamine ammonium was tested by gavage at a 

dose three times higher than the current limit dose of Guideline No. 8703700 in a developmental 

toxicity study in rats (MRID 4232091). In that study no effects on offspring were observed at 

any dose. If the rat is an insensitive species, we have made up for the insensitivity by testing up 

to 3000 mg/kg/bw, a dose where maternal toxicity was observed. Since fosamine ammonium 

has already been tested at such high doses in one species and no signs of developmental toxicity 

were observed, it is unlikely that developmental effects would be observed at the limit dose in a 

second species. Thus, based on exposure considerations and the lack of an effect at 3000 mg/kg 

bw in rats, we request EPA to waive the need for a developmental toxicity study in rabbits. 
Page 3 of 3 

HED Response: The list of reasons provided by DuPont provide insufficient basis for a waiver 

from the regulatory requirement for developmental toxicity study in a non-rodent species. HED 

does not agree with DuPont’s assertion that, given the labeled uses of fosamine ammonium, there 

will be virtually no chance for exposure to this compound via the oral route, the route used in 

developmental toxicity studies. Since fosamine ammonium herbicides are applied using high 

and low volume ground sprayers, occupational handlers are likely to be exposed to fosamine 

ammonium via the oral route. Given the potential for oral exposure, the presumption of low 

exposures via the dermal and inhalation routes, even if substantiated, would not preclude the 

need for a developmental toxicity study in a second species. It should also be noted that HED 

does not predict dermal absorption based solely on physical chemical properties. Finally, the 

fact that no effects were seen at high doses in one species does not preclude the need for a 

developmental study in a second species. OPP requires studies for multiple species because no 

one species is considered adequate as a model for human response. For these reasons, HED 

recommends against a waiver for the requirement a developmental toxicity study in non-rodent 

species. 

Comment: DuPont will consider providing a 28-day immuotoxicity study if there is a DCI for 

this endpoint. Following the approach to sex and species selection outlined in the EPA 

Memorandum of June 16, 2009, Immunotoxicity Test Guideline: Response to CropLife 

America’s Comments, DuPont thinks that the female mouse should be used, as this is EPA’s 

default when there is no data to support one sex or species over the other. 

HED Response: An immunotoxicity study is required under 40 CFR Part 158 as a part of the 

new data requirements for registration of a pesticide (food and non-food uses). HED encourages 

DuPont to submit a study protocol to the Agency for review prior to initiating the study.