### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

MEMORANDUM DATE: 09 July 20 1 3 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: Monsodium Methanearsonate (MSMA): Response to Public Comments on the Registration Review Workplan . PC Code : 013803 Deci s ion No.: 47CJ230 Petit ion No .: None Assessment Type: Single ChemicaVAggregate TXR No.: None MRID No.: None DP Barcode: 0412159 Registration No .: NA Regulatory Action : Registration Review Response to Comments Reregistration Case No.: 2395 CAS No.: 2 163-80-6 40 CFR: § 180.289 

### FROM: Donald Wilbur, Chemist

# ~ 

# U/4 -:r -4 "'do\.? Risk Assessment Branch VI Health Effects Division (7509P) 

### THROUGH: Felecia Fort, Chief 

# 1/ ( .., _L Risk Assessment Branch VI 

# 0 J,k C)O (]7!U Health Effects Division (7509P) 

### TO: Garland Waleko, Chemical Review Manager Tom Myers, Team Leader Risk Management and Implementa tion Bra nch II Pesticide Re

-Evaluation Division (7508P) The Pesticide Re-Evaluation Division (PRD) has requested the Health Effects Division (HED) respond to comments on the registration review of the herbicide monosodium methanearsonate (MSMA) (Docket Number EPA-HQ

- OPP-2013

-0107)

. Comments on the Revised HED seeping document (D. Wilbur, D4 10082, 03/ 19/20 1 3) prepared fo r the above docket were received from the Orgaruc Arsenical Products Task Force (OAPTF)

. The OAPTF is composed of registrants of pesticide products containing MSMA that develop scientific data and other information to support the registered uses of MSMA. Task Force members include Drexel Chemical Company and Luxembourg-Pamol, I nc. Each comment will be summarized below followed by an HED response.

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### 1. 

### OAPTF Comment on the MOA for Carcinogenic Effects of Inorganic Arsenic (p. 11

- 13) OAPTF believes that the presently available data are sufficient to demonstrate that arsenic does not interact with DNA, and to support a threshold MOA involving cytotoxicity and proliferation. In addition, OAPTF notes that there is significant ongoing research reg arding the mechanism of inorganic arsenic carcinogenicity. OAPTF believes it is probable that this ongoing research willprovide further support for a non-linear and threshold MOA before the NAS conducts its review. HED Response HE D appreciates this comment regarding the mode of action (MOA) fo r carcinogenic effects of inorganic arsenic (iAs). OPP was initially considering use of a joint review by the EPA Science Advisory Board (SAB) and the FIFRA Science Advisory Panel (SAP) to consider the MOA for iAs; however, since that time, the Agency has announced review of iAs by the Nat ional Academy of Sciences (NAS) 1 to be used in lieu of an SAB /SAP review. Therefore, EPA has agreed to postpone any decision regarding the MOA until such time that the NAS review is complete and the Agency has analyzed and responded to the report. 

### 2. OAPTF Comment on the Aggregate Exposure Assessments (p. 18-19) There is no reason to prepare an assessment of aggregate exposure to inorganic arsenic under the FQPA because use of MSMA on cotton is not expected to cause an increase in inorganic arsenic in food. HED Response HED appreciates this comment regarding a ggregate exposure assessments. While HED has previously concluded that the use of MSMA on cotton does not result in the transfer of iAs re sidues to meat and milk when live stock consume treated cottonseeds, the use on cotton may contribute to exposure through drinking water. In all aggregate exposure and risk assessments conducted by HED under FQPA, both food and drinking water are used together when making an aggregate safety finding. Therefore , HED will need to conduct an updated aggregate assessment incorporating food and drinking water during the registration review process. 

### 3. OAPTF Comment on the Cotton Gin Byproducts Residue Data Requirement and DCI (p. 17-18) Additional field trial data on cotton gin byproducts are not needed to support a tolerance determination, and this proposed data requirement should be omitted from the registration review D C!.

1 Additional information regarding the NAS review is available at: http: / /www8. nationa! academies. orglcp ' pro jectvieY.. aspx?key=49483 and http: //dels.nas.edu/Study-ln-Progress/Review-l RIS-Toxicological/DELS-B EST-12-0 I Page 2 of4HED Response HED appreciates this comment regarding the data requirement for cotton gin byproduct residue data and would like to clarify why these data are still required. T he submitted comment leads HED to believe that there appears to be some confusion regarding nature ofthe residue (i.e., metabolism) studies, and magnitude of the re s idue (i.e., field trial) studies. While the nature ofthe residue is understood for MSMA bas ed on submitted metaboli sm studies , magnitude of the residue studies on cotton gin byproducts have not been submitted. As a result ofa September 1996 Agency revision to the residue chemistry test guidelines, cotton gin byproducts were added as a recognized raw agricultural commodity (RAC) of cotton. Based on this revision, cotton gin byproducts were included as a livestock feedstuff that may enter the channels of trade , and thus a tolerance is required for enforcement purposes. The referenced study (MRID 43959801, 1995) has been previously reviewed by RED, but the submission pre-dates the 1996 residue chemistry guideline revision and does not contain cotton gin byproduct residue data. Further, the referenced study is a processing study for cotton, and not a field trial study, and would not have contained data on cotton gin byproducts regard less. In an effort to locate the required data, RED recentl y re -reviewed the submitted fie ld trial study for cotton (MRID 43720701, 1993) and confirmed that it also does not contain the required data on cotton gin byproducts. Based on this investigation of the available field trial data for MSMA , cotton gin byproduct residue data have not been received and are required; therefore , HED believes that the issued DCI is appropriate. 

### 4. OAPTF Comment on Modifying the Existing Tolerance Definition for MSMA (p. 19 -20) OPP should carefUll y review the practicality of its proposal to utilize an enforcement method for res idues in cottonseed and cotton hulls that measures MMA rather than total arsenic. HED Response HED appreciates this comment regarding the tolerance expression for MSMA. The Agency had previously (EPA-HQ-OPP-20 12-01 71) revised the tolerance expression to state "Compliance with the tolerance levels specified in thisparagraph i s to be determined by measuring only methanearsonic acid, from application of th e disodium and monosodium salts of methanearsonic acid, calculated as the sto ichiometric equivalent of As2

### 0 3, in or on the commodity. " The change that HED requested in the scoping document was only to remove the DSMA from the expression , as those uses have been cancelled. However, as HED continues to work through the registration review process and generate a preliminary risk assessment for MSMA , we will take this information under advisement. 

### 5. OAPTF Comment on Immunotoxicity Testing for MSMA (p. 25-26) The immunotoxicity testingfor MSMA proposed by OPP is unnecessary because available toxicity data show the N OAEL will be higher for immunological effects than for 

### those adverse effects that have alread y been adequately characterized.

Page 3 of4HED Response HED appreciates this comment regarding irnrnunotoxicity testing for MSMA. The task force is encouraged to submit a formal waiver request based on guidance located at http: / /www.epa.gov/pesticides/regulating/part 15 8-tox-data-requirement.pdf. HED will then consider that request and notify the task force if additional data are required.

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