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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON

, D .C. 2 0460 '

O FFICE OF C HEMICAL SA FETY AND P OLLUTION PR EVENTION

MEMORAND UM

Sep tember 30

, 2010

SUBJEC T: Fosamine Ammonium: Response to Comments on the Human Health Ri sk S eoping Document in Support of Regi strat ion Rev iew

P C C ode: 106701 DP Barcode : 0381730 Decision No. : 439219 Registration No. : N A Petition No. : N one Regulatory Action : Registration Review Ass essment Type: Respons e to C omment Rere gistration Case N o.: N A TXR No.: None C AS No .: 25954 -13-6 M RID No.: N one 4 0 CF R:

FROM : Becky Dai ss, B iologist

# ;:£~ Risk A ssessment Branch 4 

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H ealth E ffects Di vision ( 7509P) O ffice o f Pe sticide Programs

# OUG~. S usan Hummel

, Senior

# SCient Ri sk As se ssmen t Br anch 4 

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H ealth E ffects Di vision (7509P) O ffice o f P esticide Programs

T O: Eric Miederhoff Ri sk Mana ger R eviewer Reregistration Branch 3 Pesticide Reevaluation Division (7508P) Offi ce of Pe s ticide Program s

Attached i s Hea lth E ffects Division 's ( HED) response to c omments s ubmitted on the human h ealth ri sk as sessment status update for fo samine ammonium conducted as part of the Regi stration Re view process (0 36577 3, 12 /2/09) . A s ummary of s ubmitted comment s foll owed by HED 's re sponse i s pro vided bel ow.

Page 1 of3Page 2 of 3 Comment : The toxicity categories reported in th e scoping document for acute dermal, acute inhalation, and acute eye irritati on are incorrect. DuPont submitted new acute dermal, inhalation and irritation toxicity studies subsequent to pub lication 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 II I for Acute Eye Irritation.

HED Response : DuPont is correct. Revised acute toxicity category designations for these exposure routes based on the studies cited by DuP ont will be included in the registration review assessment conducted for fosamine ammonium.

Comment : EPA commented on the acute neurotoxici ty study in rats (MRID 42946501) saying, “rats showed clinical signs of t oxicity (diarrhea) at the low dos e and possible neurotoxic effects (slight palpebral closure and irre gular respiration) at higher dose s”. The finding of diarrhea in one animal in the low dose group should be revi ewed 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 th e absence of other function observational battery changes. These findings are more consistent wi th stress from compound related systemic toxicity a nd not neurotoxicity.

HED Response : The Human Health Risk Scoping Docume nt in Support of Registration Review summarizes findings and conclusi ons 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 as sessment conducted for the registration review of fosamine ammonium.

Comment : EPA is requesting a developmental toxici ty study in a non-rodent species for this non-food use pesticide. DuPont requests a waiverfor 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 or al route, the route used in developmental toxicity studies. Dermal absorption is expectedto be very low for such a highly water soluble compound. Inhalation exposure is also not expected to be relevant to th e doses that would be used in the non-rodent developmental toxicity stu dy. Therefore, it is difficult to see how a rabbit developmental toxicity study by oral administration would be additi ve to the risk assessment. Additionally, the reason gi ven for needing the developmental t oxicity 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 thatstudy no effects on offspring were observed at any dose. If the rat is an inse nsitive species, we have made up for the insensitivity by testing up to 3000 mg/kg/bw, a dose where maternal toxici ty was observed. Since fosamine ammonium has already been tested at suchhigh 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 DuPontprovide 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, give n 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 handler s are likely to be exposed to fosamine ammonium via the oral route. Given the poten tial 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 s econd species. It should al so 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 pr eclude 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 mode l for human response. For these reasons, HED recommends against a waiver for the requirementa 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 se x 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 mous e should be used, as this is EPA’s default when there is no data to supp ort 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 pe sticide (food and non-food uses). HED encourages DuPont to submit a study protocol to the Agen cy for review prior to initiating the study.