UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

DATE: 19 March2013 

SUBJECT: Monsodium Methanearsonate (MSMA): REVISED Registration 

Review Scoping Document for Human Health Assessments. 

PC Code: 013803 

Decision No.: 471553 

Petition No.: None 

DP Barcode: D410082 

Registration No.: NA 

Regulatory Action: Registration Review 

Assessment Type: Single ChemicaV Reregistration Case No.: 2395 

Aggregate 

TXR No.: None CAS No.: 2163-80-6 

MRID No.: None 40 CFR: §180.289 

FROM: Donald Wilbur, Chemist ~ W 1JJf::: 3 0 1(~ \3 

Nancy McCarroll, Ph.D., Senior Toxicologis;--~, lite~ .Jff )l() I j 

Shalu Shelat, Industrial Hygienist 

Risk Assessment Branch VI 

Health Effects Division (7509P) 

THROUGH: Anna Lo.::::t, Ph.D., Senior Toxicologist 1--t 2.:J- 3ft~ 1z •l3 

Felecia Fort, Chief ~ _ r 

Risk Assessment Branch VI · .e-r ~(fz_ ~ 

Health Effects Division (7509P) - U 

TO: Garland Waleko, Chemical Review Manager 

Tom Myers, Team Leader 

Risk Management and Implementation Branch II 

Pesticide Re-Evaluation Division (7508P) 

The Health Effects Division (HED) Monosodium Methanearsonate (MSMA) Registration 

Review Team has evaluated the status of the human health risk assessment for MSMA to 

determine the scope of work necessary to support Registration Review. The most recent 

risk assessment for MSMA was completed in 2006 (C. Smith, D329694, 06/2112006) as 

part of the Reregistration Eligibility Decision (RED) which was also published in 2006. 

This document was revised to clarify residue chemistry data requirements. 

Page 1 of22 
Background 

MSMA is a salt of the weak acid monomethylarsinic acid (MMA), which can also be 

called methanearsonic acid or methylarsonic acid (MAA). MSMA readily dissociates to 

MMA in water and, therefore, the majority of the exposure from the application of 

MSMA is to MMA. Dimethylarsenic acid (DMA), also known as cacodylic acid, is a 

major MSMA metabolite in plants. In addition, organic arsenical species can convert to 

inorganic arsenic (iAs) in both soil and water. HED understands that over time, and 

depending on the environmental conditions present, organic arsenical pesticides will 

biotransfonn by both methylation and demethylation. Since environmental conditions 

are variable, it is difficult to quantify organic versus inorganic arsenic residues at any 

specific point in time. Therefore, HED will evaluate exposure to MMA, DMA, and 

inorganic arsenic (iAs) in the MSMA risk assessment. 

Based on the scientific findings in the 2006 RED, EPA concluded that all uses of the 

organic arsenical pesticides (MSMA, disodium methanearsonate (DSMA), calcium acid 

methanearsonate (CAMA), and dimethylarsenic acid (DMA)) were ineligible for 

reregistration based largely on the fact that following application, they can convert to 

more toxic iAs in the soil and can therefore potentially contaminate drinking water 

through soil runoff. It was also assumed that due to the MSMA use on cotton and its 

associated animal feed items, residues of inorganic arsenic could be present in the meat 

and milk of animals that consumed these treated feed items and thus, increase the 

aggregate human dietary exposure and risk. 

In January and February 2009, EPA reached an agreement in principle with the technical 

registrants of all existing organic arsenical manufacturing-use products to eliminate, 

phase out, and/or modify certain uses. The result of this agreement was the EPA issuance 

of a revised RED in April 2009 and a cancellation order in September 2009 that 

terminated the last remaining uses of DSMA, CAMA, and DMA in the United States 

based on voluntary cancellations requested by the registrants. The order also tenninated 

certain MSMA product registrations and amended others (decreased rates and/or limited 

applications) to phase out all uses except cotton, sod farms, golf courses, and highway 

rights-of way; with the later three slated to be phased out by December 31, 2013. 

The 2009 agreement in principle also provided for a scientific peer review related to the 

carcinogenic mode of action (MOA) ofiAs prior to the final cancellation of the 

remaining MSMA uses. OPP was initially considering use of a joint review by the EPA 

Science Advisory Board (SAB) and the FIFRA Science Advisory Panel (SAP). 

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 phase out of uses on golf courses, sod 

farms, and highway rights-of-way until such time that the NAS review is complete and 

the Agency has analyzed and responded to the report. 

Additionally, in order for the MSMA use on cotton to be eligible for reregistration, the 

agreement required that certain mitigation measures be implemented to protect water 

1 Additional information regarding the NAS review is available at: 

http://www8.nationalacademies.org/cp/projectview.aspx?key=49483 and 

http://dels.nas.edu/Study-ln-Progress/Review-IRJS-Toxicologicai/DELS-BEST -12-0 I 

Page2 of22 
resources. These mitigation measures include: use limited to only two post-emergent 

applications per year of 2 pounds active ingredient per acre and maintenance of a 50·foot 

buffer zone around permanent water bodies. The registrants were also required to submit 

data indicating that residues of iAs will not enter the human food supply through the meat 

and milk of animals fed cotton by·products (undelinted seed, hulls, and/or gin trash). The 

Organic Arsenicals Product Task Force (OAPTF) prepared multiple submissions to the 

Agency in an attempt to demonstrate that no increased residues of iAs would be present 

in the meat and milk of cows. HED reviewed these data and concluded there is sufficient 

evidence to determine that the exposure of cows to seeds from cotton treated with 

MSMA, at the rate permitted by the label, is not expected to cause an increase in the 

inorganic arsenic concentration in milk or tissues (D. Wilbur, 0387095, 06/30/2011). 

Please see http://www.epa.gov/pesticides/reregistrationlorganic arsenicals fs.html for 

additional details regarding the agreement in principle as well as the background of the 

organic arsenical mitigation process. 

Executive Summary 

MSMA is a post-emergent organic arsenical herbicide which selectively controls certain 

weeds including Palmer amaranth. MSMA is currently registered for use on cotton, golf 

courses, sod farms, and highway rights-of-way. Based on these registered uses, 

exposures to MSMA may potentially occur via the dietary (food and drinking water), 

occupational (handler and post-application), and residential (post-application) exposure 

pathways and through the oral, dermal, and inhalation routes of exposure. 

Since MSMA readily dissociates to MMA, HED uses toxicity data for MMA to represent 

MSMA. The toxicity database for MMA is nearly complete with the exception of an 

imrnunotoxicity study which is required in accordance with new data requirements for 

conventional pesticide registration ( 40 CFR Part 158). The toxicity database for DMA 

via the oral route is adequate. During the registration review process, HED will 

reevaluate the points of departure (PODs), uncertainty factors (UFs), and safety factors 

(SFs) for the dietary, occupational and residential exposure assessments. Additionally, 

HED will reevaluate the carcinogenic mode of action (MOA) for iAs based on the 

findings of the NAS review as discussed above. 

The existing residue chemistry database for MSMA is complete and adequate for risk 

assessment purposes with the exception of two outstanding residue chemistry studies: 

field accumulation in rotational crops (which was previously requested in 2010) and field 

trial (residue) data on cotton gin byproducts. The qualitative nature of the residue(s) of 

MSMA in plants and animals has been adequately identified/characterized and is 

understood. The residues of concern in plants for tolerance enforcement and risk 

assessment are MSMA and DMA. HED previously determined that there is no 

reasonable expectation of finite residues in animal commodities. The current tolerance 

expression as listed in the 40 CFR§180.289(a) will need to be revised during the 

registration review process to reflect product cancellations due to mitigation measures 

from the 2006 RED and subsequent agreements with the registrants. 

The dietary exposure database is adequate to support the existing registrations. The only 

remaining food use is on cotton (via animal feed by·products). Since exposure from 

Page 3 of22 
drinking water will likely be the highest contributor to dietary risk, and iAs is the most 

prevalentlbioavailable species in water, new dietary exposure and risk assessments may 

be required during the registration review process to incorporate the findings of the NAS 

review of iAs. No acute or chronic (noncancer) risks of concern were identified in the 

2006 dietary assessment (S. Kinard, D329695, 06/21/2006) due to exposure to MSMA 

(MMA) or DMA. Cancer risks ranging from l.OE-06 to 1.0E-04 were identified when 

data from the FDA Total Diet Study (TDS) were aggregated with drinking water 

estimated concentrations. In addition to using updated drinking water estimates, any 

updated dietary exposure assessments will incorporate current consumption information, 

updated residue values, updated percent crop treated information, and any revised PoDs 

or uncertainty factors. 

The residential exposure database is complete. A revised residential exposure assessment 

may be required under registration review that includes post-application exposure to 

adults and children entering into previously treated golf courses. This assessment should 

incorporate the 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment, updated human factors (e.g., body weight) assumptions, and the appropriate 

uses patterns that are registered at the time of registration review. 

The most recently completed aggregate risk assessment was conducted in connection 

with the 2006 RED. An updated non-occupational (residential) assessment may be 

.required as use patterns have changed. It is also possible that additional data may be 

provided with which to update the drinking water assessment. Consequently, a revised 

aggregate risk assessment for MSMA may be required for registration review. 

The occupational exposure database is complete. Updated occupational handler and postapplication exposure assessments may be required under registration review based upon 

revisions to the Agency's scenario-specific surrogate handler exposure data and changes 

to the use pattern. 

Introduction 

HED has reviewed the most recent exposure and risk assessments for MSMA, as well as 

toxicity data, exposure and usage databases, and the latest Agency science policy and risk 

assessment methodologies to determine if sufficient data are available and if updates are 

needed to support registration review. Additionally, the team conducted a screeninglevel literature search for any information that would aid in assessing human health risks 

from MSMA. 

MSMA is a post-emergent organic arsenical herbicide which selectively controls certain 

weeds including Palmer amaranth. MSMA is currently registered for use on cotton, golf 

courses, sod farms, and highway rights-of-way. 

Information on the chemical identity and physicochemical properties of MSMA is 

included in Attachment 1. 

Hazard ldentificationffoxicology 

Since the RED was completed in 2006, no additional guideline studies have been 

submitted to HED for MMA or DMA. Although a data gap exists for the MMA acute 

Page 4 of22 
and subchronic neurotoxicity battery, the Agency has granted waivers to these 

requirements (TXR #0056514 ). The remaining requirement for MMA that has not yet 

been satisfied is for immunotoxicity testing. The document entitled Evaluation of the 

Potential Carcinogenicity Due to Exposure to Inorganic Arsenic was submitted by 

OAPTF in March 2012. This docwnent, which consists of studies in support of the mode 

of action (MOA) analysis of iAs-induced skin, urinary bladder and lung tumors will be 

part of the evaluation by the NAS. 

Toxicological Profile o(MMA & DMA 

The target organ following oral exposure of MMA is the gastrointestinal tract, 

particularly the large intestine. Effects such as histopathology of the cecum, rectum, 

and/or colon were noted as the most sensitive effects in chronic rat studies. MMA is 

classified as a "not likely" human carcinogen and is not mutagenic or genotoxic. 

Target organs for DMA after oral exposure are the urinary bladder and the thyroid. 

Bladder tumors are found in rats of both sexes but not in mice. Nevertheless, genetically 

engineered mouse strains, constructed for enhanced sensitivity to specific tumors types, 

showed neoplastic lesions. The mode of action (MOA) for the DMA-induced rat bladder 

tumors is cytotoxicity associated with regenerative cell proliferation. 

In the last risk assessment, the default uncertainty factor of 1 OOX (I OX for intra-species; 

lOX for inter species) was applied to all MSMA exposure scenarios. In the case of 

DMA, for oral exposures ranging from short-term to chronic duration, the last risk 

assessment included a reduction of the default I OX for inter-species (animal to human) 

extrapolation to 3X. This reduction is based on the known pharmacokinetic differences 

between rats and humans which include: differences in sequestration ofDMA111 by rat 

hemoglobin, longer retention time in rats versus humans or mice, and the increased 

urinary output in rats versus humans. 

There is no quantitative or qualitative evidence of increased susceptibility of rats or rabbit 

fetuses to in utero exposure in available developmental studies for MMA or DMA; 

therefore, the FQPA safety factor was removed. 

Conclusions for Hazard Identification/Toxicology 

The endpoints, PODs, and the uncertainty factors for MMA, DMA, and iAs will be 

reevaluated during registration review after consideration all of the currently available 

data including the NAS report regarding. iAs. 

Residue Chemistry 

The existing residue chemistry database for MSMA is complete and adequate for risk 

assessment purposes with the exception of two studies: field accumulation in rotational 

crops (which was previously requested in 20IO) and field trial (residue) data on cotton 

gin byproducts. The qualitative nature of the residue(s) ofMSMA in plants and animals 

has been adequately identified/characterized and is understood. The residues of concern 

in plants for tolerance enforcement and risk assessment are MSMA and DMA. HED 

previously determined that there is no reasonable expectation of finite residues in animal 

commodities. Adequate analytical methods exist for data collection and tolerance 

enforcement. Adequate storage stability data exist. Adequate magnitude of the residue 

Page 5 of22 
data exist for cotton with the exception of studies listed above. HED had previously 

requested residue data on undelinted cottonseed. A review of the existing data (MRJD 

43720701) indicates that HED does indeed have these data, and thus that deficiency can 

be considered resolved. 

Conclusions for Residue Chemistry 

The residue chemistry database for MSMA is adequate for risk assessment purposes with 

the exception of the studies listed above. Field accumulation in rotational crops data are 

still outstanding from a previous data call-in (DCI), while residue data on cotton gin 

byproducts data have not been included in a previous DCI and are required. All other 

residue chemistry data requirements have been adequately addressed. 

Dietary Exposure and Risks 

Acute and chronic dietary exposure and risk assessments for DMA and MMA resulting 

from food/feed uses of cacodylic acid and salts, DSMA, and MSMA were conducted (S. 

Kinard, D329695, 06/21/2006) using the Dietary Exposure Evaluation Model (DEEMFCIDTM, Version 2.03) which used food consumption data from the USDA's Continuing 

Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. All species 

of concern in the assessment (MMA, DMA, and iAs) have distinct toxicities; therefore 

exposure to each were considered individually. 

Acute Dietary Exposure and Risk 

Several acute dietary assessments were performed for the organic arsenic pesticides using 

field trial data, FDA's Total Diet Study (TDS) data, percent crop treated information, and 

default processing factors. Since arsenic is ubiquitous in the environment and was 

quantified as total arsenic in the best available data, it was not possible to detennine 

where the arsenic originated from (i.e., background or from pesticidal use) or to 

determine speciated residue values for use in a national dietary exposure assessment. 

Therefore, the assessments contained assumptions that were not standard for HED dietary 

exposure assessments. A number of the assumptions that have been made in these 

assessments may be conservative due to the lack of speciated data; however, when 

assuming that all arsenic found in the field trials, reported in the FDA TDS, and 

estimated in water is either monomethylated arsenic (MMA, resulting from 

DSMAIMSMA use) or dimethylated arsenic (DMA or cacodylic acid), risks were below 

HED's level of concern for the U.S. population and all population subgroups at the 99.9th 

percentile of exposure. 

Chronic Dietary Exposure and Risk 

Several chronic dietary assessments were performed for the organic arsenic pesticides 

using field trial data, FDA's TDS data, percent crop treated information, and default 

processing factors. Based on. the same assumptions used for the acute analysis, risks were 

below RED's level of concern for the U.S. population and all population subgroups. 

Cancer Dietary Exposure and Risk 

A dietary cancer assessment for inorganic arsenic (iAs) was not performed. However, 

based on the MMA and DMA exposure assessments, HED determined that only a small 

amount of the total arsenic exposure would be required to be from iAs to reach a cancer 

level of concern of 1 x 1 o-6

• The Q1 * determined by EPA's Office of Water for cancer 

risks from iAs exposure used in the analysis was 3.67. For additional information on iAs 

Page 6of22 
in drinking water, please go to EPA's Office ofWater website at 

http://www.epa.gov/safewater/arsenic/index.html. 

Drinking Water 

A drinking water assessment (K. Moore, 0309098, 02/0112006) was conducted by the 

Environmental Fate and Effects Division (EFED). To determine estimated drinking 

water concentrations (EDWCs) in surface water, the Pesticide Root Zone Model (PRZM 

3 .12; 5/7 /98), which simulates transport off the agricultural field, is run in tandem with 

the Exposure Analysis Modeling System, (EXAMS 2.98.04; 6/13/97), which simulates 

the fate of chemicals in the water body. EDWCs ofMMA, DMA, and iAs were provided 

for each registered use. Compounds resulting from degradation/transformation were 

considered as well as directly applied pesticides. It is impossible to determine the exact 

concentration of each species that will be present at any one time. Each species will 

reach its highest level at different times, and it is concentrations from these worst-case 

situations which were reported and used. It was not expected that the maximum 

concentrations for each compound would all be present at the same time. 

Conclusions for Dietary Exposure and Risks 

The dietary exposure database is adequate to support the existing registrations. However, 

since FDA TDS monitoring data were used, it may be necessary for HED to conduct new 

dietary exposure assessments based on a review of the existing data for MMA, DMA, and 

iAs. These new exposure assessments should include incorporating new and updated 

information and policies and any revised points of departure or uncertainty factors, 

including any revised cancer MoA information based on the NAS review of iAs. The 

revised assessment should also include updated consumption information and utilize the 

newest version ofDEEM-FCID along with incorporating any revised and updated 

drinking water estimates from EFED. 

Residential Exposure and Risk 

MSMA is currently registered for use on golf courses, sod farms, highway rights-of-way, 

and cotton. Based on these uses, adults and children (6< 11 years old and 11 <16 years 

old) may be potentially exposed to MSMA as result of contacting treated golf course turf 

(i.e., residential post-application exposure). As noted before, MSMA dissociates to 

methanearsonic acid (MMA) when mixed with water; therefore, the toxicological 

endpoints for MMA will be used in the risk assessment for assessing handler and postapplication exposures. 

In accordance with the updated Part 158 data requirements (2007), a turf transferable 

residue (TTR) study is required for all occupational (e.g., sod farms, golf courses, parks, 

and recreational areas) or residential turf uses. The registrant has submitted one TTR 

study in support ofMSMA, titled Determination o[Transferable Residues from Turf 

Treated with Monosodium Methanearsonate (MRID No. 44958901). This TTR study 

has previously been used to assess post-application risk estimates for MSMA. 

In the last occupational and residential exposure and risk assessment (C. Smith, 

D329694, 06/21/2006), residential handler and post-application exposure and risks were 

assessed for MSMA. At that time, MSMA was registered for lawn and residential 

ornamental uses which are not currently registered. The handler non-cancer risk 

Page 7 of22 
estimates did not exceed HED's level of concern (MOEs ~ 100). Post-application dermal 

exposure and risk estimates were assessed for adults, youths (11-12 years old), and 

toddlers (3 years old) along with incidental oral post-application risk estimates for 

toddlers (3 years old). The post-application non-cancer risk estimates· did not exceed 

HED's level of concern (MOEs ~ 100). 

Since the 2006 HED risk assessment, the RED addressed mitigation measures involving 

residential exposure. In 2009, an amendment to the RED outlined the deletion of 

residential turf use sites. The remaining registered uses include golf courses, sod farms, 

highway right of ways, and cotton and of those uses, golf course applications have the 

potential to result in residential exposure. As part of the mitigation, the golf course use 

was to be prohibited after 12/31/13. However, EPA has agreed to postpone any decision 

regarding the cancellation of use on golf courses until such time that the NAS review is 

complete and the Agency has analyzed and responded to the report. As part of the 

mitigation, golf course is prohibited after December 31, 2013 pending the NAS review. 

Residential exposures resulting from off-site transport (e.g., spray drift or volatilization) 

may occur as a result of applications of MSMA. The Agency is in the process of 

evaluating these types of exposures and will examine the need for spray drift and 

volatilization assessments for MSMA during registration review. 

Conclusions for Residential Exposure and Risks 

The residential exposure database is adequate to support the registration review process 

for MSMA. A revised non-cancer residential exposure assessment may be required 

under registration review that includes post-application exposure to adults and children 

exposure via commercially treated golf courses. This assessment should incorporate, as 

necessary, the 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment, updated human factors (e.g., body weight) assumptions, and the appropriate 

uses patterns that are registered at the time of registration review. 

Aggregate Exposure and Risk Assessment 

Previous aggregate assessments for the MSMA were conducted for acute, short-term, and 

long-term durations. Even though many uses have been cancelled, there is still a 

potential for short-term residential post-application exposure from the use on golf 

courses. Therefore, an updated aggregate risk assessment may be required to support the 

registration review which incorporates any new PoDs, UF/SFs, any revisions to the 

drinking water assessment, as well as the findings from the updated non-occupational 

(residential) assessment. 

Occupational Exposure and Risks 

The Agency has determined that there is a potential for occupational handler and postapplication exposures resulting from the registered uses of MSMA. As noted before, 

MSMA dissociates to :rvtMA when mixed with water; therefore, the toxicological 

endpoints for MMA were used in the risk assessment for assessing handler and postapplication exposures. 

Page 8 of22 
Occupational Handlers 

The 2006 occupational and residential risk assessment (C. Smith, D329694, 06/21/2006) 

evaluated a number of occupational handler scenarios that represented the major MSMA 

occupational handler scenarios based on application equipment and formulation type. 

Occupational handlers can be exposed to MMA by mixing, loading, or applying MSMA. 

The 2006 occupational assessment indicated that occupational handler scenarios did not 

result in risks of concern for inhalation exposure from registered uses of MSMA (MOEs 

~ 1 00). There were dermal exposure and risk estimates of concern at baseline PPE, 

however, all risk estimates were not of concern with the addition of gloves (MOEs ~ 

100). 

Since the 2006 assessment, there have been changes to the registered use pattern and 

there is new unit exposure data available to assess occupational handler scenarios. 

Because of these changes, HED will likely reevaluate the occupational handler 

assessment for MSMA. 

Occupational Post-application 

Occupational post-application workers can be exposed to MMA by entering an 

environment that has been previously treated with MSMA. The 2006 assessment 

addressed occupational post-application exposures using default assumptions instead of 

chemical specific dislodgeable foliar residue (DFR) data. All post-application scenarios 

assessed for MSMA did not exceed HED's level of concern (MOEs ~ 1 00) at day 0. The 

restricted-entry interval was set to 12-hours for use ofMSMA based on the technical 

acute toxicity category III for acute dermal toxicity, primary eye, and skin irritation. 

MSMA is not a dermal sensitizer. 

There are currently no site- or chemical-specific DFR data for MSMA. In the 2006 

assessment, HED had used standard values for DFR and dissipation in the absence of 

data. Based on the MOEs presented for post-application exposure from application to 

cotton (MOEs range from 10,000 to 36,000) and the current guidance for requiring DFR 

studies, a chemical-specific DFR study is not required at this time. 

Based on the Agency's current practices, a quantitative post-application inhalation 

exposure assessment for MSMA is not required. However, volatilization of pesticides 

may be a potential source of post-application inhalation exposure to individuals nearby 

pesticide applications. The Agency sought expert advice and input on issues related to 

volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

(FIFRA) Scientific Advisory Panel (SAP) in December 2009. The Agency received the 

SAP's fmal report on March 2, 2010 

(http://www .epa.gov /scipoly/SAP/meetings/2009/120 1 09meeting.btml). The Agency is 

in the process of evaluating the SAP report and may, as appropriate, develop policies and 

procedures to identify the need for and, subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for MSMA. 

Conclusions (or Occupational Exposure and Risks 

The occupational exposure database is complete. Updated occupational handler and postPage9 of22 
application exposure assessments may be required under registration review based upon 

revisions to the Agency's scenario-specific surrogate handler exposure dati and changes 

in the use pattern. 

Human Studies 

MSMA risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide or other chemicaL Studies such as the Pesticide 

Handlers Exposure Database, Outdoor Residential Exposure Task Force, and Agricultural 

Handler Exposure· Task Force have been reviewed by the Agency and found on the basis 

of available evidence to have been neither fundamentally unethical nor significantly 

deficient relative to standards of ethical research conduct prevailing when they were 

conducted. There is no barrier in EPA's "Protection of Human Subjects" Regulation to 

reliance on these studies. 

Endocrine Disruption Screening Program 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include 

endpoints which may be susceptible to endocrine influence, including effects on 

endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, 

fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological 

hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, 

developmental and reproductive effects in different taxonomic groups. As part of its 

reregistration decision, EPA reviewed these data and selected the most sensitive 

endpoints for relevant risk assessment scenarios from the existing hazard database. 

However, as required by FFDCA section 408(p ), MSMA is subject to the endocrine 

screening part of the Endocrine Disrupter Screening Program (EDSP). 

EPA has developed EDSP to determine whether certain substances (including pesticide 

active and ·other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a "naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate." The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to 

identify the potential of a chemical substance to interact with the estrogen, androgen, or 

thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and 

are found to have the potential to interact with E, A, or T hormonal systems will proceed 

to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests 

are necessary based on the available data. Tier 2 testing is designed to identify any 

adverse endocrine related effects caused by the substance, and establish a dose-response 

relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p ), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group 

of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

MSMA is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Accordingly, as part of registration review, EPA will issue 

2 - http://www.epa.gov/pesticides/sciencelhandler-exposure-data.html 

Page 10 of22 
future EDSP orders/data call-ins, requiring the submission of EDSP screening assays for 

MSMA. For further information on the status of the EDSP, the policies and procedures, 

the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, 

please visit our website: http://www.epa.gov/endo/. 

Public Health and Pesticide Epidemiology Data 

An updated review ofMSMA incident reports was recently prepared by HED (S. Recore, 

0406611, 11/01/2012). Based on the low frequency and mostly low severity of incident 

cases reported for metheanearsonic acid, salts in both IDS and NIOSH SENSOR, there 

does not appear to be a concern at this time that would warrant further investigation. 

However, because there were three incidents in NIOSH SENSOR-Pesticides classified as 

high severity, the Agency will continue to monitor the incident information and if a 

concern is triggered, additional analysis will be included in the risk assessment. 

Tolerance Assessment and International Harmonization 

Tolerances are established under 40 CFR §180.289 for residues ofMSMA, including its 

metabolites and degradates, in or on a variety of food and feed crops as shown in Table 

Attachment 4. The Codex Alimentarius Commission, the Canadian Pest Management 

Regulatory Agency (PMRA) and Mexico have not established maximum residue limits 

(MRLs) for MSMA or any other arsenical. A summary of the International Residue 

Limits (IRLs) for MSMA are included in Attachment 4. 

The current tolerance expression as listed in the 40 CFR §180.332 has been updated to 

reflect current HED policies. However, due to the cancellation of DMSA, it will need to 

be revised. The revised tolerance expression should be as follows: 

Tolerances are established for residues of the herbicide methane arsonic acid, including 

its metabolites and degradates, in or on the commodities in the table in this paragraph. 

Compliance with the tolerance levels specified in this paragraph is to be determined by 

measuring only methanearsonic acid, from application of monosodium salts of 

methanearsonic acid, calculated as the stoichiometric equivalent of As203, in or on the 

commodity. 

Environmental Justice 

Potential areas of environmental justice concerns, to the extent possible, were considered 

in this human health risk assessment, in accordance with U.S. Executive Order 12898, 

"Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec order 12898.pdf. The Office 

of Pesticide Programs (OPP) typically considers the highest potential exposures from the 

legal use of a pesticide when conducting human health risk assessments, including, but 

not limited to, people who obtain drinking water from sources near agricultural areas, the 

variability of diets within the U.S., and people who may be exposed when harvesting 

crops. Should these high exposures indicate potential risks of concern, OPP will further 

refine the risk assessments to ensure that the risk estimates are based on the best available 

information. 

Page 11 of22 
Cumulative Risk Assessment 

At thi~ time, EPA does not have available data to detennine whether MSMA has a 

common mechanism of toxicity with other substances. EPA has not made a common 

mechanism of toxicity finding as to MSMA and any other substances, and MSMA does 

not appear to produce a toxic metabolite produced by other substances which have 

tolerances in the U.S. Therefore, EPA has not assumed that MSMA has a common 

mechanism of toxicity with other substances. 

Data Requirements 

HED does not anticipate that additional residue chemistry, toxicology or 

occupational/residential exposure data will be required for the MSMA registration review 

process, with the exception of the following studies listed below: 

• Magnitude of the Residue (Crop Field Trials) on Cotton Gin Byproducts (GDLN 

860.1500) . 

• Immunotoxicity Study (GDLN 870.7800) 

References 

Table 1: HED Memorancbl Relevant to Regi.stratio.n Review ~ 

Author BarcodeffXR # Date Title 

J. VanAlstine 0056514 11/08/2012 Monosodium methanearsonate (MSMA): 

Summary of Hazard and Science Policy 

Council (HASPOC) meeting 

C. Smith D329696 06/21/2006 Arsenic: Final Occupational and Residential 

Exposure Assessment for the Reregistration 

Eligibility Decision Docwnent for DMA, 

CAMA, MSMA, and DSMA 

C. Smith D329694 06/21/2006 Organic Arsenicals: Final HED Combined 

Chapter of the Reregistration Eligibility 

Decision Document (RED) 

S. Kinard 0329695 06/21/2006 Organic Arsenicals. Revised Acute 

and Chronic Dietary Exposure 

Assessments for the Reregistration 

Eligibility Decision (RED) 

P.Y. Barnes D309106 01/31/2006 Residue Chemistry Chapter for the Monosidiwn 

and Disodium Salts of Methanearsonic Acid 

P.Y. Barnes 0325973 01131/2006 MAA and Salts Product Chemistry Chapter 

A. Lowit 014425 12/14/2000 Methanearsonic acid and its sodium and 

calcium salts- Report of the Hazard 

Identification Assessment Review Committee 

Attachments 

Attachment 1. Chemical Identity/Physicochemical Properties 

Attachment 2. Toxicity Profile Tables 

Attachment 3. Endpoint Tables 

Attachment 4. MSMA International Residue Limits Table 

Page 12 of22 
Attachment 1. 

Table Al.l. MSMA Nomenclature. ." ,. 

- '1J 

MSMA 

Chemical structure o, /CH3 

As 

HO/ 'o- Na+ ·Common name Monosodium methanearsonate 

Company experimental name N/A 

IUPACname Sodium hydrogen methylarsonate 

CAS name Sodium hydrogen methylarsonate 

CAS registry number 2163-80-6 

Chemical 

MMAIMAA 

structure o, /CH3 

As 

HO/ 'oH 

Monomethylarsinic acid, Methanearsonic acid 

Chemical 

DMA 

structure o, /CH3 

As 

HO/ 'cH3 

Dimethylarsenic acid, cacodylic acid 

~ 

TableA1.2. Physicochemical Properties of MSM.A. 

Parameter Value Reference 

Melting point/range 116-121 oc MSMA Product Chemistry 

pH (at2S oc) 5.5 - 5.9 Chapter (P.Y. Barnes, D 

Density 1.65 0325973, 0 1/31/2006) 

Water solubility 104 g/100 mL 

Solvent solubility gil 00 mL at 20 OC 

methanol 16 

n-hexane 0.005 

Vapor pressure 1 x 10-S Pa 

Dissociation constant, pKa 9.02 

OctanoVwater partition coefficient, <1 

Log(Kow) 

Page 13 of22 
Attachment 2. Toxicity Profile Tables --,~~ -... Th' 

,. __ 

- . -.., 

Table A2.1. Acute Toxieity ofMSMA ~ -

Stu4¥· 1)-R" 

oxicity 

6oideline NQ •. MRID#s Res.ults Ca~~f,Y,_ 

81-1 Acute Oral, rat 45405601* LDso = 2449 mglkg (F) III 

3184 mglkg (M) 

2833 m_g!!<g (Combined) 

81-2 Acute Dermal, rabbit 41890001* LDso > 2000 mg!kg III 

81-3 Acute Inhalation, rat 42604601* LCso = 2.20 mg/L III 

81-4 Primary Eye Irritation, 43840901* Reversible conjunctival III 

rabbit irritation 

81-5 Primary Skin Irritation, 41892008a Slight initant IV 

rabbit 

81-6 Dermal Sensitization, guinea 41890002* Not a sensitizer 

pig 

81-8 Acute Neurotoxicity N/A .. *Data presented m table are for formulations contammg technical MSMA. 

Page 14 of22 
870.3100 

90-Day oral toxicity 

mice 

4063260 I (1985) 

Unacceptable/Nonguideline 

0, 10, 100, 500, and 1250 ppm (0, 2.1, 

22.5, 110.6, and 288.6 mglkglday for 

males and 0, 2.8, 27.5, 137.4, and 342.5 

mglkglday for females) MMA 

870.3200 41872701 (1991) 

21128-Day dermal toxicity Acceptable/Guideline 

rabbits 0, l 00, 300, or 1000 mglkglday MMA 

870.3465 

28/90-Day inhalation 

toxicity 

870.3700a 

Prenatal developmental 

rats 

870.3700b 

Prenatal developmental 

rabbits 

870.3800 

Reproduction and fertility 

effects 

rats 

Not available for MMA 

41926401 (1990) 

Acceptable/Guideline 

0, 10, 100, or 500 mg!kg!day MMA 

15939001 (1986) 

Acceptable/Guideline 

0, I, 3, 7, 12 mglkglday MMA 

43178301 (1994) 

Acceptable/Guideline 

0, 100, 300, or 1000 ppm. 

FO: 5.8, 17.8, and 63.5 mglkglday, 

respectively, for males and 7.5, 22.5, and 

77.6 mglkglday for females. 

F1: 6.5, 21.1, and 75.8 mg!kglday, 

respectively, for males and 7.9, 25.4, and 

Page 15 of22 

Based on the data presented in this study, a LOAEL 

and NOAEL cannot be established. The numerous 

deficiencies in the conduct of this study preclude 

meaningful evaluation of the data. 

Systemic toxicity NOAEL =1000 

Systemic toxicity LOAEL > 1000 

Dermal irritation NOAEL =1000 

Dermal irritation LOAEL > 1000 

Maternal toxicity NOAEL = 10 mglkglday. 

Maternal toxicity LOAEL = 100 mglkg!day, based 

on decreased body weight gain and food 

consumption. 

Developmental toxicity NOAEL= 100 mglkglday. 

Developmental toxicity LOAEL = 500 mglkglday, 

based on decreased mean fetal body weight. 

Maternal toxicity NOAEL = 7 mg!kglday. Maternal 

toxicity LOAEL = 12 mglkg!day, based on 

decreased body weight, food consumption (during 

the dosing period), and abortions. 

Developmental toxicity NOAEL = 7 mglkglday. 

Developmental toxicity LOAEL = 12 mglkglday, 

based abortions and on an increased incidence of 

skeletal variations (increased numbers of 13th 

thoracic vertebra with ribs and gtb lumbar vertebra). 

Parental NOAEL = 100 ppm for males and 300 

ppm) for females. 

Parental LOAEL =300 ppm for male rats and 1000 

ppm for female rats based on increased food 

consumption with decreased body weight gain 

along with whole litter loss. 

Reproductive NOAEL = 300 ppm. Reproductive 

LOAEL > 300 ppm. 
[IT able A2.2. Profile of Subchronic, Chrome, and Other Toxicity of MMA 

., 

• 

MMA 

Guidelllle #-/Study Type 

MRID# (year) !Classification/Doses Results -

88.6 mglkglday for females. MMA 

OffspringNOAEL- 100 ppm. 

Offspring LOAEL = 300 ppm based on increased 

pup death (day 0-21), reduced litter survival index, 

and decreased lactation index related to whole litter 

loss. 

870.4200b 40546101 and41266401 (1988) NOAEL- 2 mglkg/day. 

Chronic toxicity Acceptable/Guideline LOAEL = 8 mglkg/day based on based on body 

dogs 0, 2.5, 10,40 mglkg!day (week 1 only) weight gain and kidney effects (organ weight and 

0, 2, 8, and 35 mglkg/day (week 2-52) 'histopathology) in females in both sexes 

MMA 

870.4300 41669001 (1990) NOAEL = 50 ppm (3.2 mglkglday for males and 

Combined Chronic/ Acceptable 3.8 mglkg/day for females) 

Carcinogenicity 0, 50,400 and 800-1300 ppm (0, 3.2, 27.2, LOAEL = 400 ppm (27 .2 mglkglday for males and 

rats and 93.1 mglkglday for males and 0, 3.8, 32.9 mglkglday for females) based on decreased 

32.9, and 10 1.4 mglkg!day for females) for body weights, body weight gains, food 

104 weeks. MMA consumption, histopathology of gastrointestinal 

tract and thyroid. 

Dosing was considered adequate. 

870.4300 42173201 (1991) NOAEL = 50 ppm (9.3 and 12 mglkg/day) for 

Carcinogenicity Acceptable males and females. 

mice 0, 10, 50, 200, and 400 ppm (0, 1.8, 9.3, LOAEL = 200 ppm (38 and 46 mglkg/day) for 

38, and 83 mglkglday for males and 0, 2.2, males and females based on decrease in body 

12, 46, and 104 mglkg/day for females) weight gain, increased water consumption, and 

MMA histopathology of the kidney. 

Dosing was considered adequate. 

870.5100 41651902 (1989) There was no evidence of induced mutant colonies 

Gene mutation Acceptable/Guideline over background. 

Salmone/la typhimurium In deionized distilled water at 

reverse gene mutation concentrations ofO, 667, 1000. 3333, 6667 

and 10,000 IJ.g/plate +/-S9 

870.5300 41651904 (1989) MMA was tested up to cytotoxic concentrations. 

Gene mutation Acceptable/Guideline There was no evidence of induced mutant colonies 

Mouse lymphoma assay In deionized water at 0, 300, 400, 534, over background. 

712,949, 1266, 1688,2250, 3000 and 

4000 ~J.g/mL -S9 and at 0, 7 1, 95, 127, 

169,225,300,400,534,712,949,1266 

and 1688 ug/mL +S9 

Page 16 of22 
-cc 

T•ble.Al~. Profile of Subchronic, Chronic., and .Other Toxicity of ~ j 

MMA 

GuideliDe--~ /Study Type . ~ 

MRID# (year} /~eatioDIDoses Results -

870.5375 41651903 (1989) MMA was tested up to a slightly cytotoxic 

Chromosomal aberration Acceptable/Guideline concentration, limited by solubility in the solvent, 

Mouse micronucleus assay In distilled water in two independent distilled water. There was no evidence of 

assays. Concentrations tested in the initial chromosomal aberrations induced over background. 

assay were 0, 625, 1250, 2500, 5000 

J.!g/mL, with and without metabolic 

activation (S9-mix) 

870.5550 4 [ 651905 (1989) There was no evidence that unscheduled DNA 

Unscheduled DNA Acceptable/Guideline synthesis, as determined by radioactive tracer 

Synthesis In deionized distilled water at procedures [nuclear silver grain counts} was 

concentrations ofO, 10, 50, 100, 500, 750 induced. 

and 1000 p.glmL for 18 to 20 hours in an 

initial and a confrrmatory assay. 

870.6200a Not available for MMA 

Acute neurotoxicity rat 

870.6200b Not available for MMA 

Subchronic (13 weeks) 

neurotoxicity screening 

battery rat 

870.7485 42010501 (1991) Analysis offecal and urinary samples by HPLC and 

Metabolism and Acceptable/Guideline TLC revealed that the radioactivity of all 

pharmacokinetics In water at concentrations ofO, 5.0, or preparative fractions was associated with parent 

dogs 200.0 mglkg according to the following compound and two unknown metabolites. The 

five different dose groups: I) In the major product excreted in both urine and feces was 

vehicle control group, dosed with water by unchanged parent, accounting for 80-97% of the 

gavage; 2) a single radiolabeled gavage administered dose. 

dose of 5.0 mg/kg; 3) a single radio labeled 

gavage dose of 200 mg/kg; 4) dosed by 

gavage for 14 consecutive days with 

unlabelled MSMA at 5.0 rnglkglday 

followed by a single radiolabeled dose of 

MSMA at MSMA; 5) a single 

radiolabeled i.v. dose of 5.0 mglkg. 

MSMA in rats 

870.7600 Not available for MMA 

Dermal penetration 

870.7800 Not available for MMA 

Immunotoxicity 

NOAEL = no observed adverse effect level; LOAEL = lowest observed adverse effect level; FQPA SF = 

FQPA Safety Factor; PAD = population adjusted dose ( c = chronic); LOC = level of concern; MOE = 

Margin of exposure. 

Page 17 of22 
Att c h a men t3 . E d ' t T D lPOID a bl es 

TableA3.1. Summary of Toxie.oJogical Doses and Endpoints for MMA for Use in Dietary and NonOccupational Human Rbk Assessments• 

kposure Poiotof Uaeert.inty/ RID, PAD, Level of 

FQPASafety Coocera. for Stady and Toxieological E.tleets Sceoario Departure Fa¢or Risk Assessment 

NOAEL = UF,.. = 10 Chronic Toxicity in Dog, MMA study (MRID# 

Acute Dietary 10 mglkg UFH = 10 Acute RID = 0.1 mglkg 40546101) 

(general (week 1 only) FQPASF= IX aPAD = 0.1 mglkg 

LOAEL = 40 mglkg/day based on clinical signs of 

population) diarrhea and vomiting observed in the first of week 

of dosing with 2-5 hours of each days dosing. 

UFA = 10 Chronic Toxicity Rat, MMA study (MRID# 

UFH = 10 41669001) 

NOAEL= Chronic RID = Rat LOAEL = 27.2 mglkglday for males and 32.9 Chronic Dietary 3.2 mglkg/day FQPA SF= IX 0.1 mglkg mglkg/day for females based on decreased body (all populations) 

c PAD = 0.03 mglkg weights, diarrhea, body weight gains, food 

consumption, histopathology of gastrointestinal tract 

and thyroid. 

UFA = 10 Rabbit developmental toxicity, M:MA study (MRID# 

Incidental Oral NOAEL= UFH = 10 15939001) 

Short-Term 7 mg/kg/day FQPASF= IX 

Residential LOC = 1 00 LOAEL = 12 mglkglday, based on decreased body 

(1 - 30 days) weight, food consumption (during the dosing period), 

and abortions. 

Incident al Oral UFA = 10 Chronic Rat, MMA study (MRID# 41669001) 

Intermediate- NOAEL= UFH = 10 Residential LOC = 100 LOAEL = 27.2 mglkg/day for males and 32.9 

Term 3.2 mglkglday FQPA SF= IX mglkglday for females based on decreased body 

(1 - 6 months) weights, diarrhea. 

Dermal UFA = 10 

Short-Term UFH = 10 21-Day Dennal Toxicity in Rabbit, M:MA study (1- 30 days) Dennal NOAEL= FQPA SF= IX Residential LOC = 100 (MRJD# 41872701) 

Intermediate- 1000 mglkglday LOAEL > 1000 mglkg/day. Term 

(1- 6 months) 

Dermal 

Long-Term Not applicable 

(> 6 months) 

Inhalation A = 10 90-Day Inhalation with DMA • Rat (MRID# 

Short-Term Inhalation NOAEL= UFH = 10 4470030I)b 

(1- 30 days) 0.01 mg/L FQPA SF = IX Residential LOC "" 1 00 LOAEL = 0.034 mglkg/L (14.95 mglkglday) based 

Intermediate- (4.38 mglkg/day, on presence of moderate and marked 

Term adjusted) intracytoplasmic eosinophilic granules (lEG) in the 

(1 - 6 months) nasal turbinate cells of male and female rats. 

Cancer Classification: "not likely human carcinogen" 

. . • Abbreviations: 

Point of Departure (POD) A data point or an estimated point that is derived from observed dose-response data and used to mark 

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation 

from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). MOE = margin of exposure. LOC =level of concern. N/A = not applicable. UF =uncertainty factor. FQPA SF 

=Special FQPA safety factor. PAD = population adjusted dose (a= acute, c = chro.nic). RID = reference dose. MOE= margin of 

.exposure. 

bUsed as surrogate for MMS 

Page 18 of 22 
Table .A3.2. Summary of Toxicological Doses and Endpoinu for MMA Use in o~~upational Human Risk 

Assessments• 

w·~intyt ~ 

Exposure Poiatof RfD, PAD, Level of 

FQPASafety Coacern for Study ·aad Toxicologkal Effects Seeuario Departure Factor Rbk Assessmeat 

Dermal UFA = 10 

Short-Term UFH = 10 21·Day Dermal Toxicity in Rabbit, MMA study (1-30 days) Dermal NOAEL= FQPASF= IX Occupational LOC = (MRID# 41872701) 

Intermediate- 1000 mglkglday 100 LOAEL > 1000 mglkglday. Term 

(I - 6 months) 

Dermal Not applicable 

Long-Term 

(> 6 months) 

Inhalation UFA = 10 90-Day Inhalation with DMA - Rat {MRlD# 

Short-Term Inhalation NOAEL= UFH= 10 4470030l)b 

(1- 30 days) 0.01 mg!L FQPA SF= IX Occupational LOC = LOAEL = 0.034 mglkg/L (14.95 mglkglday) based 

Intermediate- (4.38 mglkglday, 100 on presence of moderate and marked 

Term adjusted) intracytoplasmic eosinophiJic granules (lEG) in the 

(1 - 6 months) nasal turbinate cells of male and female rats. 

Cancer Classification: "not likely human carcinogen" 

• Abbreviations: 

Point of Departure (POD)= A data point or an estimated point that is derived from observed dose-response data and used to mark 

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation 

from animal to human (interspecies). · UFH = potential variation in sensitivity among members of the human population 

(intraspecies). MOE= margin of exposure. LOC =level of concern. N/A = not applicable. UF =uncertainty factor. FQPA SF 

= Special FQPA safety factor. PAD = population adjusted dose (a= acute, c =chronic). RID reference dose. MOE = margin of 

exposure. 

bUsed as surrogate for MMA 

Page 19 of22 
TableA3.3. Summary of Toxicological Doses and Endpoints for DMA for Use iD Dietary and Non-Occupational 

Human Risk Assessments • 

EXPQSUre Point of Uneertaiaty/ ~Um),PAJ>,~dof 

&eurio FQPA.Safdy Concera fOJ' Study and Toiicol~ Effects Depa~ Faetot Risk· Asiessmeot 

Rat Developmental Toxicity study (MRID# 

40625701) 

LOAEL = 36 mglkglday based on decreased fetal 

UFA = IO weights, shorter crown-rump length, the suggestion 

Acute Dietary NOAEL = of diaphragmatic hernias and delayed/lack of 

(general 12 mglkg UFH= IO Acute RID = 0.12 mglkg ossification o numerous bones. 

population) FQPA SF= IX aPAD = 0.12 mglkg Rabbit Developmental Toxicity study (MRID# 

40663301) 

LOAEL = 48 mglkglday based on mortality, 

abortions, body weight loss and reduced food 

consumption. 

BMDLIO = UFA=3 Chronic RID = Chronic Dietary 0.43 mglkglday UFH = 10 O.l4mglkg BMD10 of0.92 mglkglday for BrdU labeling from 

(all populations) FQPA SF= IX cPAD = 0.14 mglkg 

Arnold et al (1999) 

Rat Developmental Toxicity study (MRID# 

40625701) 

LOAEL = 36 mglkglday based on decreased fetal 

UFA = IO weights, shorter crown-rump length, the suggestion 

Incidental Oral of diaphragmatic hernias and delayed/lack of 

Short-Term NOAEL= UFH = 10 LOC = 100 ossification o numerous bones. 

{I- 30 days) 

12 mglkglday FQPA SF= IX Rabbit Developmental Toxicity study (MRID# 

40663301) 

LOAEL = 48 mglkglday based on mortality, 

abortions, body weight loss and reduced food 

consumption. 

Incidental O ral UFA =3 

Intermediate- BMDLto= UFH = IO LOC = 30 BMD10 of0.92 mglkglday for BrdU labeling from 

Term 0.43 mglkglday FQPA SF = IX Arnold et a! ( 1999) 

(I- 6 months) 

Dermal UFA = 10 21-Day Dermal Toxicity in Rabbit, MMA study 

Short-Term UFH= 10 (MRID# 41872801) 

(1- 30 days) Dermal NOAEL= FQPA SF= IX LOC = 100 LOAEL = I 000 mglkglday based on decreased body 

Intermediate- 300 mglkglday weights gain in females, and decreased testicular 

Term weights, hypospermia, and tubular hypoplasis in 

(1 - 6 months) males. 

Dermal 

Long-Term Not required 

(> 6 months) 

Inhalation UFA = 10 90-Day Inhalation with DMA - Rat (MRID# 

Short-Term Inhalation NOAEL= UF8 = 10 44700301) 

(1 - 30 days) 0.01 mg!L FQPA SF = IX LOC = 100 LOAEL = 0.034 mglkg!L (I4.95 mglkglday) based 

Intermediate- (4.38 mglkglday, on presence of moderate and marked 

Term adjusted) intracytoplasmic eosinophilic granules (IEG) in the 

(1 - 6 months) nasal turbinate cells of male and female rats. 

Cancer Classification: No carcinogenic at doses that do not result I enhanced cell proliferation. 

.. a Abbreviations: 

Page 20 of22 
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark 

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation 

from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). MOE= margin of exposure. LOC = level of concern. N/A = not applicable. UP = uncertainty factor. FQPA SF 

= Special FQPA safety factor. PAD= population adjusted dose (a= acute, c =chronic). RID = reference dose. MOE= margin of 

exposure. BMD =Benchmark Dose. BMDL =Lower 95% confidence on the BMD. 

Table.A3.4. Summary of Toxicological Doses and Endpoints for DMA Use in Occupational Human Risk 

.Assessme~ts· __ o 

Exposure Point of Uncertainty/ RID, PAD, Le:vel of 

FQPASafety Con~ru for Study and Toxicological E«ects 

j Scenario Departure Factor Risk Assessment 

Dermal UFA = 10 ~Day Dermal Toxicity in Rabbits study (MRID# 

Short-Term UFH = 10 41872801) 

(1-30 days) Dermal NOAEL= FQPA SF= IX LOC = 100 LOAEL = 1000 mglkglday based on decreased body 

Intermediate- 300 mglkglday weights gain in females, and decreased testicular 

Term weights, hypospennia, and tubular hypoplasis in 

(1 - 6 months) males. 

Dermal Not applicable 

Long-Term 

(> 6 months) 

Inhalation UFA = 10 90-Day Inhalation with DMA - Rat (MRID# 

Short-Term Inhalation NOAEL= UFH = 10 44700301) 

(1 - 30 days) 0.01 mg!L FQPASF= 1X LOC = 100 LOAEL = 0.034 mglkg/L (14.95 mglkglday) based 

Intermediate- (4.38 mglkglday, on presence of moderate and marked 

Term adjusted) intracytoplasmic eosinophilic granules (lEG) in the 

(1 - 6 months) nasal turbinate cells of male and female rats. 

Cancer Classification: Not carcinogenic at doses that do not result in enhanced cell proliferation. 

.. • AbbreVIations: 

Point of Departure (POD}= A data point or an estimated point that is derived from observed dose-response data and used to mark 

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation 

from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). MOE = margin of exposure. LOC =level of concern. N/A =not applicable. UF = uncertainty factor. FQPA SF 

=Special FQPA safety factor. PAD= population adjusted dose {a= acute, c = chronic). RID = reference dose. MOE= margin of 

exposure. 

Page 21 of22 
Attachment 4. MSMA International Residue Limits Table 

Monosodium methanearsonate (MSMA) (013803; 10/15/2012) 

Summazy of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

us Canada Mexicoz Codex3 

40 CFR 180.289: None None 

Plant: methanearsonic acid (calculated as 

A~ 0 3 ) from application of the disodium 

and monosodium salts of methanearsonic 

acid 

Commodity1 Tolerance (ppm) !Maximum Residue Limit (mg/kg) 

us Canada Mexico.t Codex.) 

Cotton undelinted seed 0.7 

Cotton, hulls 0.9 

Completed: M. Negussie; 10/18/2012 

1 Includes only commodities of interest for this action. Tolerance values should be the HED 

recommendations and not those proposed by the applicant. 

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 

3 • = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP 

= processed postharvest treated commodity, such as processing of treated stored wheat. (fat)= to be 

measured on the fat portion of the sample. MRLs indicated .as proposed have not been finalized by the 

CCPR and the CAC. 

Page 22 of22