UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: 09 July 2013 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Monsodium Methanearsonate (MSMA): Response to Public Comments 

on the Registration Review Workplan. 

PC Code : 013803 

Decision No.: 47CJ230 

Petition 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.: 2163-80-6 

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 Implementation Branch 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, D410082, 03/19/2013) prepared for 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, Inc. 

Each comment will be summarized below followed by an HED response. 

Page 1 of 4 
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 regarding the mechanism of inorganic arsenic carcinogenicity. OAPTF believes 

it is probable that this ongoing research will provide further support for a non-linear and 

threshold MOA before the NAS conducts its review. 

HED Response 

HED appreciates this comment regarding the mode of action (MOA) for 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 National 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 aggregate exposure assessments. While HED 

has previously concluded that the use of MSMA on cotton does not result in the transfer 

of iAs residues to meat and milk when livestock 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 FQP A, 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 DC!. 

1 Additional information regarding the NAS review is available at: 

http:/ /www8. nation a! academies. orgl cp'pro j ectvieY.. aspx?key=4 9483 and 

http://dels.nas.edu/Study-ln-Progress/Review-l RIS-Toxicological/DELS-B EST -12-0 I 

Page 2 of4 
HED 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. The 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 residue (i.e., field trial) 

studies. While the nature of the residue is understood for MSMA based on submitted 

metabolism studies, magnitude of the residue studies on cotton gin byproducts have not 

been submitted. As a result of a 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 regardless. In an 

effort to locate the required data, RED recently re-reviewed the submitted field 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 carefUlly review the practicality of its proposal to utilize an enforcement 

method for residues 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-2012-01 71) revised the tolerance expression to 

state "Compliance with the tolerance levels specified in this paragraph is to be 

determined by measuring only methanearsonic acid, from application of the disodium 

and monosodium salts of methanearsonic acid, calculated as the stoichiometric 

equivalent of As20 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 NOAEL will be higher for immunological effects than for 

those adverse effects that have already been adequately characterized. 

Page 3 of4 
HED 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. 

Page 4 of4