Revised Reregistration
Eligibility Decision for
MSMA, DSMA,
CAMA, and Cacodylic
Acid
August 10, 2006
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
MEMORANDUM
Date: August 10, 2006
Subject: Revised "Reregistration Eligibility Decision for MSMA, DSMA, CAMA,
and Cacodylic Acid" Document
From: Lance Wormell, Chemical Review Manager
Reregistration Branch 2
Special Review and Reregistration Division
To: Organic Arsenical Herbicides Docket (EPA-HQ-OPP-2006-0201)
EPA originally published the "Reregistration Eligibility Decision for MSMA, DSMA,
CAMA, and Cacodylic Acid" (EPA 738-R-06-021) in the electronic docket on August 9,
2006. EPA has since identified and corrected a typographical error on page 22. The
cancer slope factor for inorganic arsenic used to calculate the exposure level in drinking
water was incorrectly listed as 3.67 x 10"3 (mg/kg/day)"1. The value has since been
corrected to 3.67 (mg/kg/day)"1. The typographical change in the document does not alter
EPA's calculations or conclusions and the current document should be used in place of
the previous version.
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United States Office of Prevention, Pesticides EPA 738-R-06-021
Environmental Protection And Toxic Substances July 2006
Agency (7508P)
Re registration Eligibility
Decision for MSMA,
DSMA, CAMA, and
Cacodylic Acid
ListB
Case Nos. 2395, 2080
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Reregistration Eligibility Decision (RED) Document
for
MSMA, DSMA, CAMA,
and Cacodylic Acid
Approved by:.
Debra Edwards, Ph. D.
Director
Special Review and
Reregistration Division
Date: Tti^x 31. 2 (TO L
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TABLE OF CONTENTS
I. Introduction 7
II. Chemical Overview 8
A. Regulatory History 9
B. Use Profile 10
1. Formulations 11
2. Application Methods 12
3. Usage 12
III. Summary of Organic Arsenical Herbicides Risk Assessments 12
A. Background, Organic, Inorganic, and Total Arsenic 12
1. Background Arsenic 13
2. Organic Arsenic 14
3. Inorganic Arsenic 14
4. Total Arsenic 15
B. Human Health Risk Assessment 15
1. Toxicity Profile 15
2. Dietary Exposure and Risk from Food and Drinking Water 22
3. Residential Exposure and Risk 27
4. Aggregate Risk 28
5. Cumulative Risk Assessment 31
6. Occupational Risk 32
7. Incident Reports 33
C. Environmental Risk Assessment 33
1. Environmental Fate and Transport 34
2. Environmental Effects 36
3. Ecological Incidents 39
4. Endangered Species Risk 39
IV. Risk Management, Reregistration, and Tolerance Reassessment Decisions.... 39
A. Public Comments and Responses 39
B. Benefits and Alternatives 40
1. Cotton 40
2. Turf. 41
3. Other Uses 41
C. Determination of Reregistration Eligibility and Regulatory Rationale 41
1. Reregistration Eligibility Decision 41
2. Regulatory Rationale for EPA's Reregistration Eligibility Decision 42
D. Food Quality Protection Act Findings and Regulatory Rationale 43
1. FFDCA/FQPA Findings 43
2. Regulatory Rationale for FFDCA/FQPA Findings 45
E. Policy Considerations 45
V. What Registrants Need to Do 46
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MSMA, DSMA, CAMA, and Cacodylic Acid Reregistration Team
Office of Pesticide Programs:
Biological and Economic Analysis Division
Bill Phillips
Derek Berwald
Elisa Rim
Jenna Carter
Skee Jones
Environmental Fate and Effects Risk Assessment
Keara Moore
Thuy Nguyen
Dan Rieder
Health Effects Risk Assessment
Bill Smith
Sherrie Kinard
Anna Lowit
Yvonne Barnes
Bill Hazel
Registration Division
Jim Tompkins
Risk Management
Lance Wormell
Dirk Helder
Margaret Rice
Office of General Counsel:
Pesticides and Toxic Substances Law Office
Gautam Srinivasan
Bob Perils
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Glossary of Terms and Abbreviations
AGDCI
ai
aPAD
AR
BCF
CFR
cPAD
CSF
CSFII
DCI
DEEM
DFR
DWLOC
EC
EDWC
EEC
EPA
EXAMS
EUP
FCID
FDA
FIFRA
FFDCA
FQPA
FOB
G
GENEEC
GLN
HAFT
IR
LD50
LOC
LOD
LOAEL
Agricultural Data Call-In
Active Ingredient
Acute Population Adjusted Dose
Anticipated Residue
Bioconcentration Factor
Code of Federal Regulations
Chronic Population Adjusted Dose
Confidential Statement of Formula
USDA Continuing Surveys for Food Intake by Individuals
Data Call-In
Dietary Exposure Evaluation Model
Dislodgeable Foliar Residue
Drinking Water Level of Comparison.
Emulsifiable Concentrate Formulation
Estimated Drinking Water Concentration
Estimated Environmental Concentration
Environmental Protection Agency
Exposure Analysis Modeling System
End-Use Product
Food Commodity Intake Database
Food and Drug Administration
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Food Quality Protection Act
Functional Observation Battery
Granular Formulation
Tier I Surface Water Computer Model
Guideline Number
Highest Average Field Trial
Index Reservoir
Median Lethal Concentration. A statistically derived concentration
of a substance that can be expected to cause death in 50% of test
animals. It is usually expressed as the weight of substance per
weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
Median Lethal Dose. A statistically derived single dose that can be
expected to cause death in 50% of the test animals when
administered by the route indicated (oral, dermal, inhalation). It is
expressed as a weight of substance per unit weight of animal, e.g.,
mg/kg.
Level of Concern
Limit of Detection
Lowest Observed Adverse Effect Level
Micrograms Per Gram
Micrograms Per Liter
Page 5 of 46
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mg/kg/day
mg/L
MOE
MRID
MUP
NA
NAWQA
NPDES
NR
NOAEL
OP
OPP
OPPTS
PAD
PCA
PDF
PHED
PHI
ppb
PPE
ppm
PRZM/EXAMS
Qi*
RAC
RED
REI
RfD
RQ
SCI-GROW
SAP
SF
SLC
SLN
TGAI
TRR
USDA
USGS
UF
UV
WPS
Milligram Per Kilogram Per Day
Milligrams Per Liter
Margin of Exposure
Master Record Identification (number). EPA's system of recording
and tracking studies submitted.
Manufacturing-Use Product
Not Applicable
USGS National Water Quality Assessment
National Pollutant Discharge Elimination System
Not Required
No Observed Adverse Effect Level
Organophosphate
EPA Office of Pesticide Programs
EPA Office of Prevention, Pesticides and Toxic Substances
Population Adjusted Dose
Percent Crop Area
USDA Pesticide Data Program
Pesticide Handler's Exposure Data
Preharvest Interval
Parts Per Billion
Personal Protective Equipment
Parts Per Million
Tier II Surface Water Computer Model
The Carcinogenic Potential of a Compound, Quantified by EPA's
Cancer Risk Model
Raw Agriculture Commodity
Reregi strati on Eligibility Decision
Restricted Entry Interval
Reference Dose
Risk Quotient
Tier I Ground Water Computer Model
Science Advisory Panel
Safety Factor
Single Layer Clothing
Special Local Need (Registrations Under Section 24(c) of FIFRA)
Technical Grade Active Ingredient
Total Radioactive Residue
United States Department of Agriculture
United States Geological Survey
Uncertainty Factor
Ultraviolet
Worker Protection Standard
Page 6 of 46
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I. Introduction
This document is the Environmental Protection Agency's (EPA or "the Agency")
reregi strati on eligibility determination (RED) and tolerance reassessment for all currently
registered uses of MSMA, DSMA, CAMA, and cacodylic acid (collectively referred to as
the "organic arsenical herbicides"). This document summarizes the human health and
environmental risks as well as the tolerance reassessment for the organic arsenical
herbicides.
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended
in 1988 to accelerate the reregi strati on of products with active ingredients registered prior
to November 1, 1984. The amended act calls for the development and submission of data
to support the reregi strati on of an active ingredient, as well as a review of all data
submitted to the Environmental Protection Agency. Reregi strati on involves a thorough
review of the scientific database underlying a pesticide's registration. The purpose of the
Agency's review in this case is to reassess the potential risks arising from the currently
registered uses of the organic arsenical herbicides, to determine the need for additional
data on health and environmental effects, and to determine whether or not the pesticides
meet the "no unreasonable adverse effects" criteria of FIFRA.
EPA's decision under FIFRA is based on a thorough evaluation of both the risks
and benefits of the uses of the organic arsenical herbicides. While EPA has identified
some risk associated with the direct use of these herbicides, the Agency's primary
concern is the potential for applied organic arsenical products to transform to a more
toxic inorganic form of arsenic in soil with subsequent transport to drinking water. The
Agency's risk assessment - bolstered by actual field monitoring data in both surface and
ground water - estimates levels of arsenic in drinking water from pesticidal uses that
raise a concern for cancer risk. Given that estimated drinking water exposure from the
pesticidal uses alone exceeds EPA's level of concern and that alternative herbicides are
readily available, EPA concludes that the benefits do not outweigh the risks and that all
uses for the active ingredients MSMA, DSMA, CAMA, and cacodylic acid are ineligible
for reregi strati on.
The Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food
Quality Protection Act (FQPA), requires EPA to reassess by August 3, 2006 all tolerances
that were in effect as of August 3, 1996. In order for a pesticide tolerance to remain in
effect, EPA must generally determine with reasonable certainty that no harm will result
from aggregate exposure to the pesticide chemical residue.
Given that estimated drinking water exposure from the pesticidal uses alone
exceeds EPA's level of concern, EPA concludes that existing tolerances listed under 40
CFR §180.289 (a)(l) and 40 CFR §180.311 (a)(l) do not meet the reasonable certainty of
no harm standard under FFDCA/FQPA.
Page 7 of 46
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Risks summarized in this document are those that result only from the use of the
organic arsenical herbicides. The Food Quality Protection Act (FQPA) requires that, when
considering whether to establish, modify, or revoke a tolerance, the Agency consider
"available information" concerning the cumulative effects of a particular pesticide's
residues and "other substances that have a common mechanism of toxicity." Unlike other
pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to
the organic arsenical herbicides. EPA has not assumed that the organic arsenical herbicides
share a common mechanism of toxicity with other compounds. For information regarding
EPA's efforts to determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the policy statements released by
EPA's Office of Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common mechanism of
toxicity on EPA's website at http://www.epa.gov/pesticides/cumulative/.
The document consists of six sections: Section I (Introduction) contains the
regulatory framework for reregi strati on/tolerance reassessment; Section II (Chemical
Overview) gives an overview of the chemicals and their uses; Section III (Summary of
Organic Arsenical Herbicides Risk Assessments) summarizes the human health and
ecological risk assessments; Section IV (Risk Management, Reregi strati on, and
Tolerance Reassessment Decisions) presents the Agency's reregi strati on eligibility,
tolerance reassessment, and risk management decisions; Section V (What Registrants
Need to Do) presents next steps for the registrants; and the appendices that list related
support documents and other information. Risk assessments and other support
documents cited in this RED are available at http://www.regu!ations.gov in docket
number EPA-HQ-OPP-2006-0201.
II. Chemical Overview
The registered pesticides assessed in this RED, collectively referred to as the
"organic arsenical herbicides," are monosodium methanearsonate (MSMA), disodium
methanearsonate (DSMA), calcium acid methanearsonate (CAMA), cacodylic acid
(dimethylarsinic acid), and cacodylic acid's sodium salt (sodium cacodylate). For ease of
discussion, the sodium salt of cacodylic acid and cacodylic acid are treated as one and are
also referred to as dimethylarsonic acid (DMA). MSMA, DSMA, and CAMA are
collectively referred to as monomethylarsonic acid (MMA, also known as MAA or
methylarsonic acid). In cases where chemical-specific issues are discussed, the
individual pesticide name (i.e., MSMA, DSMA, or CAMA) is used. Table 1 presents the
chemicals assessed in the organic arsenic herbicide RED.
Table 1. Registered Pesticides Assessed in the Organic arsenical herbicides RED
Case
Number
2395
2395
CAS
Number
2163-80-6
144-21-8
PC Code
013803
013802
Chemical Name
monosodium methanearsonate
disodium methanearsonate
Name Used in
RED Documents
MSMA
DSMA
MMA or DMA
MMA
Page 8 of 46
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2395
2380
2380
5902-95-4
75-60-5
124-65-2
013806
012501
012502
calcium acid methanearsonate
cacodylic acid
cacodylic acid, sodium salt
CAMA
cacodylic acid
DMA
A. Regulatory History
The organic arsenical herbicides were first registered in the United States for use
as herbicides in the 1950s (DSMA) and 1960s (MSMA, CAMA, cacodylic acid).
Currently there are approximately 90 end-use products containing MSMA, 25 end-use
products containing DSMA, 4 end-use products containing CAMA, and 35 end-use
products containing cacodylic acid. There are currently 3 tolerances for MSMA and
DSMA (expressed as methanearsonic acid) listed in Chapter 40 of the Code of Federal
Regulations (40 CFR) 180.289 and 1 tolerance for cacodylic acid listed in 40 CFR
180.311; no tolerance exists for CAMA. Previously, tolerances existed for cacodylic acid
on milk, meat, poultry, and eggs (MMPE). These MMPE tolerances were revoked in
February 2004 (40 CFR Part 180 [OPP-2003-0344; FRL-7338-3]).
Tolerances previously existed for several inorganic arsenical pesticides (e.g., lead
arsenate). EPA conducted a Special Review in several phases for the various uses of
inorganic arsenical pesticides based primarily on concern for carcinogenicity. The last
remaining uses - including lead arsenate used as a growth regulator on citrus, calcium
arsenate used as an herbicide on turf, sodium arsenite used as a fungicide on grapes and
arsenic acid used as a desiccant on okra for seed and cotton - were voluntarily cancelled
in the late 1980s and the early 1990s, and the associated tolerances have been revoked.
Historically, the use of arsenic acid on cotton had been as high as 6.8 million pounds of
active ingredient per year.
In addition, the U.S. Food and Drug Administration (FDA) has established
tolerances for total arsenic in edible tissues and in eggs of chickens and turkey as well as
in edible tissues of swine as listed in 21 CFR 556.60. Accordingly, EPA's dietary
analyses include estimates of possible arsenic residues in poultry and swine commodities
making use of monitoring data from the FDA Total Diet Study. The poultry and swine
tolerances listed in 21 CFR 556.60 are regulated by FDA and are not included in or
affected by this tolerance reassessment decision.
The reregi strati on of MSMA is being supported by Albaugh, Inc. and the MAA
Research Task Force (MAATF) comprising APC Holdings Corp., KMG-Bernuth, Inc.,
and Luxembourg-Pamol, Inc.; DSMA is being supported by the MAATF; CAMA is
being supported by APC Holdings Corp.; and cacodylic acid is being supported by
Luxembourg-Pamol, Inc. The organic arsenical herbicides are not registered for use in
the European Union or in Canada. MSMA was previously registered in Canada for
forestry use (tree-injectable only). The registrant did not provide the necessary
supporting data in 2003 and the products were listed as "discontinued" as of August
2005. Existing products may not be used after December 2008. Cacodylic acid was
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previously registered in Canada from 1968 to 1972. CAMA was registered in Canada as
an insecticide from 1928 to 1972.
Data Call-Ins (DCI) for MSMA, DSMA, CAMA, and cacodylic acid were issued
in 1991, 1993, and 1995. The DCIs required chemical identity, toxicology, field trial,
ecological, and other data.
B.
Use Profile
MSMA and DSMA are herbicides registered for weed control on cotton, for turf
grass and lawns, and under trees, vines, and shrubs. CAMA is an herbicide registered for
post-emergent weed control on lawns. Cacodylic acid is a defoliant and herbicide
registered for weed control under non-bearing citrus trees, around buildings and
sidewalks, and for lawn renovation. A summary of the uses supported for reregi strati on
and assessed in EPA's RED is presented in Table 2. These uses reflect the information in
the proposed Master Labels submitted by the MAATF in December 2005. The proposed
Master Labels are available at http://www.regulations.gov in docket number EPA-HQ-
OPP-2006-0201.
Table 2. Summary of Organic Arsenical Herbicide Uses Evaluated for Reregi strati on
Chemical
MSMA
Use Site
Cotton
Grasses Grown for
Seed in Pacific
Northwest only
(Ryegrass, Fescue,
and Bluegrass)
Lawns, Ornamental
Turf, and Sod Farms
Nonbearing Orchards
and Vineyards
Noncrop Areas
Application Methods
By ground or air: pre-plant or post-
plant (up to cracking); by ground
or air: post-emergent (as over the
top broadcast spray); by ground:
post-emergent (directed spray
application)
Pacific Northwest apply before
boot stage
By ground only on athletic fields,
golf courses, parks; by ground on
well established actively growing
turf; by ground on established
Bermuda grass & zoysiagrass; sod
farms
Ground directed
Ground application
Application
Rates (Ib. ai/A)1
0.8- 1.7
5.3
1.9-3.4
3.5
3.9
Applications
Per Year
1-2
1
4
3
4
Page 10 of 46
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DSMA
CAMA2
Cacodylic
acid
Cotton
Grasses Grown for
Seed in Pacific
Northwest only
(Ryegrass, Fescue,
and Bluegrass)
Lawns, Ornamental
Turf, and Sod Farms
Nonbearing Orchards
and Vineyards
Noncrop Areas
Turfgrass, Lawns,
Ornamental Turf,
Turf Grown for Sod
Cotton
Lawns, Ornamental
Turf
Non-Crop Areas,
Ornamentals
Nonbearing Citrus
By ground or air pre-plant or post-
plant (up to cracking); by ground
or air: post-emergent (as over the
top broadcast spray); by ground
post-emergent (directed spray
application); by ground post-
emergent (directed band
application) based on 40 inch row
spacing)
Pacific Northwest apply before
boot stage
By Ground on well established
actively growing turf; sod farms
Ground directed
Ground application
By ground only on athletic fields,
golf courses, parks; by ground on
well established actively growing
turf; by ground on established
Bermuda grass and zoysiagrass
Preconditioning for defoliation,
defoliation
Lawn renovation, lawn edging
Non-crop; ornamentals
Ground directed
1.7
o o
J.J
2.5
3.7
3.9
2.2-4.4
0.9375-2.0
7.3-7.7
7.3
4.96
1-2
1
4
3
4
2-4
1-2
2-4
6
3
1 Application rates for MSMA, DSMA, and CAMA are expressed as MMA equivalent
2 One broadcast application per year with additional applications as spot treatment only; in Florida all
applications as spot treatment only
1. Formulations
MSMA is formulated as a liquid concentrate and a ready-to-use liquid. DSMA is
formulated as a liquid concentrate and a wettable powder. CAMA is formulated as a
liquid concentrate and a ready-to-use solution. Cacodylic acid is formulated as a liquid
concentrate, a pressurized liquid, and a ready-to-use solution. There are approximately
250 registered products.
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2. Application Methods
MSMA and DSMA are applied by aircraft, groundboom, rights-of-way sprayer,
turf handgun sprayer, low pressure handwand sprayer, and sprinkler can. CAMA is
applied by commercial applicators using a low-pressure handwand sprayer or handgun
sprayer and is applied by homeowner applicators using a low pressure handwand sprayer,
hose-end sprayer, and ready-to-use "trigger pump" sprayer. Cacodylic acid is applied
using aircraft, groundboom sprayer, rights-of-way sprayer, handgun sprayer, low pressure
handwand sprayer, and sprinkling can.
3. Usage
Each year approximately 3,000,000 pounds of MSMA or DSMA and 100,000 pounds
of cacodylic acid are applied in the US based on EPA's Screening Level Use Analysis
data; no data are available for CAMA. The majority of the organic arsenical herbicides is
applied to cotton and turf (residential and golf courses).
III. Summary of Organic Arsenical Herbicides Risk Assessments
The purpose of this section is to summarize EPA's human health and ecological
risk conclusions for the organic arsenical herbicides to help the reader better understand
EPA's risk management decisions. The full risk assessments and related supporting
documents are available at http://www.regulations.gov in docket number EPA-HQ-OPP-
2006-0201.
A. Background, Organic, Inorganic, and Total Arsenic
The element arsenic is ubiquitous and occurs naturally in many forms in the
environment. In addition to these naturally occurring "background" (i.e., non-pesticidal)
levels of arsenic, the RED document and support documents consider "organic arsenic,"
"inorganic arsenic," and "total arsenic." For ease of discussion, background arsenic
refers to arsenic in the environment that is not as a result of organic arsenical pesticide
use; organic arsenic refers to MMA (MSMA, DSMA, CAMA) and/or DMA (cacodylic
acid); inorganic arsenic refers to the more toxic form found in water and soil; and total
arsenic refers to the non-differentiated or "unspeciated" measure of arsenic (including
background, organic, and inorganic) commonly used in regulatory levels.
Because arsenic is ubiquitous and exists in many forms in the environment, it is
difficult to quantify the extent to which measured arsenic is organic versus inorganic and
the extent to which measured arsenic - whether organic, inorganic, or total - is present
due to organic arsenic herbicide use versus naturally occurring (i.e., background). To the
extent possible, EPA considered background, organic, inorganic, and total arsenic in its
assessments. However, concerns for cancer risk from drinking water were based on
exposure from the pesticidal use alone. Due to the complex nature of arsenic
transformation and the inability to distinguish between pesticidal and background
contributions, EPA relied on conservative assumptions to estimate exposure and risk.
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Below are several terms and definitions to keep in mind when reading this
document and support documents:
Background arsenic: "Background" arsenic is used to describe arsenic in the
environment that is present as a result of natural geological processes and/or as a
result of anything other than organic arsenical herbicide use.
Organic arsenic: The "organic" form of arsenic includes the pesticides cacodylic
acid, MSMA, DSMA, and CAMA; organic arsenic compounds can also be found
naturally in the environment.
Inorganic arsenic: Found naturally in the environment, the "inorganic" form of
arsenic is the more toxic form and is known to cause cancer in humans.
Total arsenic: "Total" arsenic is used to describe all the arsenic present in a sample
regardless of its form (i.e., organic arsenic + inorganic arsenic) and source (i.e.,
background + pesticidal); EPA and state/Federal agencies measure and/or establish
regulatory limits in soil and water for total arsenic.
Transformation: The process of arsenic changing forms (i.e., organic to inorganic
or vice versa).
Speciating: Quantifying the concentration of inorganic and organic arsenic in a soil
or water sample (as opposed to only total arsenic); "speciated" data provide a
breakdown of organic and inorganic arsenic whereas "unspeciated" data provide
only total arsenic.
Methylation and demethylation: The chemical process that transforms metals
such as arsenic by the addition (methylation) or removal (demethylation) of methyl
groups (CH3) to the molecule.
Monomethyl methanearsonate (MMA): MMA refers to organic arsenic
compounds with a single methyl group; in these assessments, the term "MMA" is
used collectively to refer to MSMA, DSMA, and CAMA (salts of MMA that readily
dissociate to MMA in water).
Dimethyl methanearsonate (DMA): DMA refers to organic arsenic compounds
with two methyl groups such as cacodylic acid and its salt; since cacodylic acid and
cacodylic acid salt are the only registered dimethyl organic arsenic herbicides, DMA
and cacodylic acid are used interchangeably in this document.
1. Background Arsenic
Arsenic can be found everywhere but is found only occasionally as the free
element because if its reactivity; instead, arsenic is usually found chemically combined as
organic and inorganic compounds in soil, water, plants, animals, and products of decay or
metabolism. The primary natural source of arsenic is from bedrock; it is also emitted
from industrial processes such as smelting and results from various agricultural practices.
EPA previously registered inorganic arsenic pesticides but these uses have since been
cancelled.
Although it is possible to measure arsenic concentrations in water, soil, and air,
arsenic introduced locally through human activities (e.g., applying organic arsenical
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herbicides) cannot be distinguished from arsenic that is present in the natural background.
Likewise, arsenic resulting from the transformation of other arsenic sources that are
either naturally present or introduced by human activities cannot be distinguished from
arsenic resulting from pesticidal applications. Thus, background levels of arsenic are
merely averages of individual snapshots of the arsenic concentrations that cannot be
quantitatively attributed to natural and human activities (e.g., historical pesticidal uses,
smelting).
Existing background surface water and groundwater arsenic concentrations can
range from several parts per billion (ppb) to more than 50 ppb. Soil and sediment arsenic
concentrations typically range from several parts per million (ppm) to more than 50 ppm.
Arsenic concentrations in air range from 0.01 g/m3 to as high as 0.75 g/m3.
Concentrations can be even higher in areas near bedrock outcrops and mine spoilings
(water and soil) or in smelter emissions (air).
As discussed above, background arsenic concentrations cannot be quantitatively
attributed to natural and human activities and are highly variable, so background arsenic
cannot be expressed as a meaningful national average. However, EPA did consider
background arsenic exposure in its dietary exposure estimates. For food, EPA used data
in the FDA Total Diet Study (TDS) which measured all detectable arsenic including
arsenic present from all pesticidal and background sources; thus, background arsenic
exposure in food is reflected in the dietary risk estimates that used FDA TDS data. For
residential, occupational, and ecological risk assessments EPA sought to assess impacts
from use of the pesticide only.
2. Organic Arsenic
In this document, organic arsenic refers to the organic arsenical herbicides
MSMA, DSMA, CAMA, and cacodylic acid. A detailed discussion of the properties of
and estimated exposure to these chemicals is included in Section II and Section III of this
document, respectively.
3. Inorganic Arsenic
As discussed above, arsenic exists in many different forms in the environment
including organic and inorganic. Organic arsenic forms (e.g., MMA, DMA) and
inorganic forms of arsenic have dissimilar toxicities and target organs. Inorganic arsenic
is more toxic than organic arsenic. Exposure to inorganic arsenic can occur from
background residues and, given time and under environmental conditions that favor the
transformation to inorganic arsenic, the registered uses of the organic arsenicals. In some
media (food, water, soil) and in some parts of the United States, the likelihood of
exposure to inorganic arsenic is higher than in others.
Under FQPA, the Agency is required to consider all potential sources of exposure
to the organic arsenicals and their metabolites and/or transformation products. Since
monitoring reflects total arsenic (all species included) and there is potential for
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transformation and exposure to inorganic arsenic from the registered uses of the organic
arsenicals, EPA performed a dietary (drinking water only) analysis for potential exposure
to inorganic arsenic.
4. Total Arsenic
Total arsenic refers to the non-differentiated or unspeciated measure of arsenic.
In monitoring programs, arsenic concentrations are typically measured and reported as
total arsenic, regardless of the species (e.g., DMA, MMA, inorganic arsenic) or mixture
of species that may be present, and regardless of the sources (i.e., pesticidal or
background) that contributed to the total arsenic level.
The federal government and most states have established limits and/or screening
levels for total arsenic exposure from a variety of sources such as drinking water, air, and
soil. These limits or screening levels are established based on long-term human health
risks from exposure to the more toxic inorganic form of arsenic and some also take into
account technically feasible clean-up levels.
EPA estimated total arsenic that may be present as a result of organic arsenical
herbicide use to allow for comparison to the Agency's established levels of concern.
B. Human Health Risk Assessment
EPA has conducted a human health risk assessment for the organic arsenical
herbicides to support the reregistration eligibility decision. EPA evaluated the submitted
toxicology, product and residue chemistry, and occupational/residential exposure studies
as well as available open literature and determined that the data are adequate to support a
reregistration eligibility decision. A summary of the human health risk assessment
findings and conclusions is provided below; the full risk assessment is available at
http://www.regulations.gov in docket number EPA-HQ-OPP-2006-0201.
1. Toxicity Profile
The toxicological databases for MMA (MSMA, DSMA, and CAMA) and DMA
(cacodylic acid) are adequate to support a reregistration eligibility decision. MMA and
DMA are considered lexicologically unique and were evaluated separately. Inorganic
arsenic, a transformation product of MMA and DMA, is also lexicologically unique and
was also evaluated separately. Data are sufficient for all exposure scenarios and for
FQPA evaluation. Additional toxicity studies are not required.
The separation of MMA, DMA, and inorganic arsenic toxi cities was the subject of
a September 2005 EPA Scientific Advisory Board meeting
(http://www.epa.gov/sab/panels/arsenic_review_panel.htm). Additional information on
the distinct toxicities of organic arsenic (i.e., MMA and DMA) and inorganic arsenic is
available in EPA's "Revised Science Issue Paper: Mode of Carcinogenic Action for
Page 15 of 46
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Cacodylic Acid (Dimethylarsinic Acid, DMAV) and Recommendations for Dose
Response Extrapolation" dated January 30, 2006.
a. Acute Toxicity Profiles
MSMA, DSMA, CAMA, and cacodylic acid have moderate to low acute toxicity
via the oral, dermal, and inhalation routes (Category III and IV). They are moderate eye
irritants (Category III), mild dermal irritants (Category IV), and not skin sensitizers.
Tables 3, 4, 5, and 6 present the acute toxicity profiles for MSMA, DSMA, CAMA, and
cacodylic acid, respectively.
Table 3. Acute Toxicity Profile for MSMA
Guideline No.
81-1
81-2
81-3
81-4
81-5
81-6
81-8
Study Type
Acute Oral, rat
Acute Dermal, rabbit
Acute Inhalation, rat
Primary Eye Irritation,
rabbit
Primary Skin Irritation,
rabbit
Dermal Sensitization, guinea
pig
Acute Neurotoxicity
MRID
45405601*
41890001*
42604601*
43840901*
418920083
41890002*
Results
LD50 = 2449 mg/kg (F)
3184mg/kg(M)
2833 mg/kg (Combined)
LD50 > 2000 mg/kg
LC50 = 2.20 mg/L
Reversible conjunctival
irritation
Slight irritant
Toxicity
Category
III
III
III
III
IV
Not a sensitizer
N/A
Table 4. Acute Toxicity Profile for DSMA
Guideline No.
81-1
81-2
81-3
81-4
81-5
81-6
81-8
Study Type
Acute Oral, rat
Acute Dermal, rabbit
Acute Inhalation, rat
Primary Eye Irritation,
rabbit
Primary Skin Irritation,
rabbit
Dermal Sensitization, guinea
pig
Acute Neurotoxicity
MRID
41892004
41892005
41892006
41892007
41892008
41890009
Results
LD50= 1935(1631-2295)
mg/kg (M&F)
LD50 > 2000 mg/kg
LC50 > 6 mg/L
Redness and swelling of the
conjunctivae
No redness or swelling
Toxicity
Category
III
III
IV
III
IV
Not a sensitizer
N/A
Page 16 of 46
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Table 5. Acute Toxicity Profile for CAMA
Guideline No.
81-1
81-2
81-3
81-4
81-5
81-6
81-8
Study Type
Acute Oral, rat
Acute Dermal, rat
Acute Inhalation, rat
Primary Eye Irritation,
rabbit
Primary Skin Irritation,
rabbit
Dermal Sensitization, rabbit
Acute Neurotoxicity
MMD
42880201
42900101
42900102
42900202
42900203
42900103
Results
LD50 > 5000 mg/kg (M&F)
LD50 > 5000 mg/kg
LC50 > 5 mg/L
Mild eye irritant
Slight skin irritant
Toxicity
Category
IV
IV
IV
III
IV
Not a sensitizer
N/A
Table 6. Acute Toxicity Profile for Cacodylic Acid
Guideline No.
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
Study Type
Acute Oral
Acute Dermal
Acute
Inhalation
Primary Eye
Irritation
Primary Skin
Irritation
Dermal
Sensitization
MRID
41925601
41892701
41892702
41892703
41892704
41892705
Results
LD50 (M&F) = 2800 mg/kg
LD50 > 2000 mg/kg
LC50 (4 hr):combined = 4.9
mg/L; M = 5.8 mg/L & F =
4.0 mg/L
Primary eye irritant -
conjunctiva! redness in 1 hr.
In al animals; persisted for 24
hrs. In 1/6 animals.
Negligible irritation in 0.5 hr.
Cleared 24 - 48 hrs.
Toxicity
Category
III
III
IV
III
IV
Not a sensitizer
b. Toxic Effects and Carcinogenicity
The target organs following oral exposure to MMA (MSMA, DSMA, CAMA) are
believed to be the gastrointestinal tract, particularly the large intestine, and the kidney.
The target organs following oral exposure to DMA (cacodylic acid) are believed to be the
bladder and thyroid.
MMA is classified as "no evidence for carcinogenicity" based on the lack of
evidence of carcinogenicity in rats and mice. DMA is classified as "not carcinogenic up
to doses resulting in regenerative proliferation." Therefore, quantification of cancer risk
is not required and a cancer analysis was not performed for MMA or DMA.
Page 17 of 46
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The metabolite inorganic arsenic is classified as a "human carcinogen;" therefore,
quantification of cancer risk is required and a cancer analysis was performed for
inorganic arsenic.
c. FQPA Considerations
The Food Quality Protection Act (FQPA) directs EPA, in setting pesticide
tolerances, to use an additional tenfold (lOx) margin of safety to take into account
potential pre- and postnatal toxicity and completeness of the data with respect to
exposure and toxicity to infants and children. FQPA authorizes EPA to modify this
tenfold safety factor only if reliable data demonstrate that the revised safety factor will be
safe for infants and children.
Acceptable developmental studies in rats and rabbits along with a two-generation
reproductive toxicity study are available for MMA. Results of developmental and
reproductive toxicity studies provided no indication of increased susceptibility. The
toxicology database is considered complete for the evaluation of sensitivity of the
developing young. A developmental neurotoxicity study is not required. Toxicity to
gastrointestinal tract and kidney provide the critical effects for MMA following oral
exposures. These effects are more sensitive than toxicities noted in other studies,
including developmental and reproductive toxicity and neurotoxicity. Therefore, the
FQPA factor can be reduced to Ix. Further, EPA has adequate data and has included
protective assumptions in its assessments to ensure that exposures are not underestimated.
Acceptable developmental studies in rats and rabbits along with a two-generation
reproductive toxicity study are available for DMA. Results of developmental and
reproductive toxicity studies provided no indication of increased susceptibility. The
toxicology database is considered complete for the evaluation of sensitivity of the
developing young. A developmental neurotoxicity study is not required. Regarding
potential thyroid toxicity, a comparative thyroid study in adult and juvenile animals is not
expected to provide endpoints more sensitive than the bladder mode of action studies
currently available. The bladder is a sensitive target organ and special mode of action
studies provide health protective endpoints for DMA toxicity at low doses. Thus, a
comparative thyroid study in juvenile and adult animals is not required. Based on the
overall weight of the evidence, the FQPA factor can be reduced to Ix.
d. Toxicological Endpoints
i. Organic Arsenic Toxicological Endpoints
The toxicological endpoints used in the human health risk assessment for MMA
and DMA are presented in Table 7 and Table 8, respectively. The uncertainty and safety
factors used to account for interspecies extrapolation, intraspecies variability, and for
completeness of the data with respect to exposure and toxicity to infants and children
(FQPA Safety Factor) are also presented in the tables below.
Page 18 of 46
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For acute and chronic exposure to MMA, EPA estimated risk using the traditional
NOAEL approach. For chronic exposure to DMA, EPA estimated risk using a
benchmark dose (BMD) approach. When available, BMDs are preferred over the
NOAEL/LOAEL because BMDs generally more accurately identify the dose at which
toxicological effects are observed. The NOAEL approach depends to an extent on the
doses included in a study. Moreover, the NOAEL approach does not account for the
uncertainty in the estimate of the dose-response. Benchmark dose analysis attempts to
model the dose-response relationship with a dose-response curve that can be described by
a mathematical function. The dose-response curve that is estimated based on the
experimental observations is used to estimate the magnitude of the response for any dose
within the experimental dose range.
Table 7. Summary of MMA Toxicological Endpoints
Exposure
Scenario
Dose Used in Risk
Assessment, UF
Level of Concern for
Risk Assessment
Study and Toxicological Effects
Dietary Risk Assessment
Acute Dietary
(general population)
Chronic Dietary
(all populations)
NOAEL = 10 mg/kg
UF = 100
FQPA SF = 1
NOAEL=
3.2 mg/kg/day
UF = 100
FQPA SF = 1
Acute RfD & PAD
= 0.1 mg/kg
Chronic RfD & PAD =
0.03 mg/kg/day
Chronic Toxicity in Dog, MMA study
(MRID# 40546101)
LOAEL = 40 mg/kg/day based on
clinical signs of diarrhea and vomiting
observed in the first of week of dosing
with 2-5 hours of each days dosing.
Chronic Toxicity Rat, MMA study
(MRID# 41669001)
Rat LOAEL = 27.2 mg/kg/day for
males and 32.9 mg/kg/day for females
based on decreased body weights,
diarrhea, body weight gains, food
consumption, histopathology of
gastrointestinal tract and thyroid.
Occupational and Residential Risk Assessment
Incidental Oral
Short-Term
(1 - 30 days)
Incidental Oral
Intermediate-Term
(1-6 months)
Dermal
Short-Term
(1 - 30 days)
Intermediate-Term
(1-6 months)
Dermal
Long-Term
(> 6 months)
NOAEL=
7 mg/kg/day
FQPA SF = 1
NOAEL=
3.2 mg/kg/day
FQPA SF = 1
Dermal NOAEL= 1000
mg/kg/day
FQPA SF = 1
LOC = 100
LOC = 100
LOC = 100
Rabbit developmental toxicity study
(MRID# 15939001)
LOAEL = 12 mg/kg/day, based on
decreased body weight, food
consumption (during the dosing
period), and abortions.
Chronic Rat study (MRID# 41669001)
LOAEL = 27.2 mg/kg/day for males
and 32.9 mg/kg/day for females based
on decreased body weights, diarrhea.
21 -Day Dermal Toxicity in Rabbit,
MMA study (MRID# 41872701)
LOAEL > 1000 mg/kg/day.
Not applicable
Page 19 of 46
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Exposure
Scenario
Inhalation
Short-Tcrni
(1 - 30 days)
Intermediate-Term
(1-6 months)
Dose Used in Risk
Assessment, UF
Inhalation NOAEL=
0.01 mg/L
(4.38 mg/kg/day,
adjusted)
FQPA SF = 1
Level of Concern for
Risk Assessment
LOC = 100
Study and Toxicological Effects
90-Day Inhalation with DMA - Rat
(MRID# 44700301)
LOAEL = 0.034 mg/kg/L (14.95
mg/kg/day) based on histopathology of
nasal cells (i.e., presence of moderate
and marked intracytoplasmic
eosinophilic granules in nasal turbinate
cells of male and female rats).
Cancer Classification
"No evidence for carcinogeniciry"
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect
level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c =
chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable
Table 8. Summary of DMA Toxicological Endpoints
Exposure
Scenario
Dose Used in Risk
Assessment, UF
Level of Concern for
Risk Assessment
Study and Toxicological Effects
Dietary Risk Assessment
Acute Dietary
(females 13-49 and
general population)
NOAEL = 12
mg/kg/day
UF = 100
FQPA SF = 1
Acute RfD = 0.12
mg/kg/day
Developmental Toxicity - Rat
(40625701)
LOAEL = 36 mg/kg/day based on
decreased fetal weights, shorter
crown-rump length, the suggestion
of diaphragmatic hernia and
delayed/lack of ossification of
numerous bones.
Developmental Toxicity - Rabbit
(40663301)
LOAEL = 48 mg/kg/day based on
mortality, abortions, body weight
loss and reduced food consumption.
Chronic Dietary
(all populations)
BMDL10 = 0.43
mg/kg/day
UF = 301
FQPA SF = 1
Chronic RfD = 0.014
mg/kg/day
BMD10of 0.92 mg/kg/day based on
regenerative proliferation of the
bladder epithelial from Arnold et al
(1999)
Page 20 of 46
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Exposure
Scenario
Dose Used in Risk
Assessment, UF
Level of Concern for
Risk Assessment
Study and Toxicological Effects
Occupational and Residential Risk Assessment
Incidental Oral
Acute-Term
(1 day)
Incidental Oral Short-
Term
(1 - 30 days)
Intermediate-Term
(1-6 months)
Dermal
Short-Term
(1 - 30 days)
Intermediate-Term
(1-6 months)
Dermal
Long-Term
(> 6 months)
Inhalation
Short-Term
(1 - 30 days)
Intermediate-Term
(1-6 months)
Inhalation
Long-Term
(> 6 months)
NOAEL = 12
mg/kg/day
FQPA SF = 1
BMDL10 = 0.43
mg/kg/day
FQPA SF = 1
Dermal NOAEL=
300 mg/kg/day
FQPA SF = 1
LOC = 100
LOC = 30
LOC = 100
Developmental Toxicity - Rat
(40625701)
LOAEL = 36 mg/kg/day based on
decreased fetal weights, shorter
crown-rump length, the suggestion
of diaphragmatic hernia and
delayed/lack of ossification of
numerous bones.
Developmental Toxicity - Rabbit
(40663301)
LOAEL = 48 mg/kg/day based on
mortality, abortions, body weight
loss and reduced food consumption.
BMD10of 0.92 mg/kg/day based on
regenerative proliferation of the
bladder epithelial from Arnold et al
(1999)
21-Day Dermal - Rabbit (41872801)
LOAEL = 1000 mg/kg/day based on
decreased body weight gain in
females, and decreased testicular
weights, hypospermia, and tubular
hypoplasia in males.
Not required
Inhalation NOAEL=
0.01 mg/L (4.38
mg/kg/day, adjusted)
FQPA SF = 1
LOC = 100
90-Day Inhalation - Rat (44700301)
LOAEL = 0.034 mg/kg/L (14.95
mg/kg/day) based on presence of
moderate and marked
intracytoplasmic eosinophilic
granules (IEG) in the nasal turbinate
cells of male and female rats.
Not required
Cancer Classification
"Not carcinogenic at doses that do not result in enhanced cell proliferation"
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect
level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c =
chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable
1 The database supports reduction of the default lOx inter-species extrapolation to 3x for chronic dietary
exposure. The key events of the rat bladder tumor mode of action are expected to be operational in humans
Page 21 of 46
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and it is further expected that at a similar dose at the target site (i.e., bladder urothelial) humans and rats
will respond in a pharmacodynamically similar way. In the December 2005 draft SAB report, the panel
provides support for reducing the default lOx interspecies factor to "some number less than 10" and that the
"EPA could assemble a case for toxicodynamic equivalency between the test species, rats, and humans
from existing experimental data."
ii. Inorganic Arsenic Toxicological Endpoints
Inorganic arsenic is classified as a "human carcinogen;" therefore, quantification
of cancer risk is required and a cancer analysis was performed. Epidemiological data
show that increased lung cancer mortality was observed in multiple human populations
exposed primarily through inhalation. Also, increased mortality from multiple internal
organ cancers (liver, kidney, lung, and bladder) and an increased incidence of skin cancer
were observed in populations consuming drinking water high in inorganic arsenic.
EPA estimates lifetime cancer risk using the estimated exposure and the
carcinogenic potential of the compound (Qi* or cancer slope factor). The risk is
expressed as a probability of developing cancer (e.g., one-in-a-million or 1 x 10"6). To
evaluate potential lifetime cancer risk resulting from exposure to inorganic arsenic in
drinking water, EPA estimated the inorganic arsenic exposure resulting from pesticidal
uses and compared the estimated risk to EPA's LOG.
To derive the LOG, EPA used the cancer slope factor for inorganic arsenic to
calculate the exposure level in drinking water (expressed as ppb) that would be below 1 x
10"6 excess cancer risk. For this risk assessment, an oral cancer slope factor of 3.67
(mg/kg/day)~* was used. This value is based on the Agency's risk assessment associated
with inorganic arsenic in drinking water presented in 2000. It is consistent with the slope
factor used by the EPA Office of Water for the arsenic maximum contaminant level
(MCL) and in OPP's 2003 Draft Preliminary Report entitled, "A Probabilistic Risk
Assessment for Children Who Contact CCA-Treated Playsets and Decks." Based on the
3.67 (mg/kg/day)"1 cancer slope factor, OPP's level of concern for exposure to inorganic
arsenic in drinking water is equivalent to 0.02 ppb or one-in-a-million (1 x 10"6) excess
cancer risk.
2. Dietary Exposure and Risk from Food and Drinking Water
Because arsenic is ubiquitous and exists in many forms in the environment, it is
difficult to quantify the extent to which measured arsenic is organic versus inorganic and
the extent to which measured arsenic - whether organic, inorganic, or total - is present
due to organic arsenic herbicide use versus naturally occurring (i.e., background levels).
Because of the complexities of separating or "speciating" arsenic in food and drinking
water and the differences in toxicity, EPA conservatively estimated dietary risk assuming
that 100% of the exposure could be to organic arsenic or inorganic arsenic. These
estimates may overestimate organic arsenic or inorganic arsenic exposure and risk
because the exposure is known to be to a combination of organic and inorganic arsenic
compounds.
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EPA's organic arsenic dietary risk assessment estimates acute (single-day) and
chronic (lifetime) toxicity to humans from ingesting a pesticide through food and
drinking water sources. Because MMA (MSMA, DSMA, CAMA) and DMA (cacodylic
acid) are not carcinogens at exposure levels expected in humans, EPA estimated acute
and chronic non-cancer dietary risk. Non-cancer dietary risk is expressed as a percentage
of a level of concern. The level of concern is the dose at or below which no unreasonable
adverse health effects to any human population subgroup are expected to occur. This
dietary level of concern is termed the population adjusted dose (PAD), which reflects the
reference dose (RfD), either acute or chronic, adjusted for (divided by) the FQPA safety
factor. Estimated risks that are less than 100% of the PAD are below EPA's level of
concern. The acute PAD (aPAD) is the highest predicted dose to which a person could
be exposed on a single day with no expected adverse health effect. The chronic PAD
(cPAD) is the highest predicted dose to which a person could be exposed over the course
of a lifetime with no expected adverse health effect.
Because inorganic arsenic is a known human carcinogen, EPA estimated cancer
risk from dietary exposure to the inorganic arsenic alone that could result from pesticide
uses alone. EPA's inorganic arsenic dietary risk assessment first estimates lifetime
cancer risk to humans from ingesting the inorganic arsenic metabolite through drinking
water sources. Since drinking water exposure alone is problematic, food sources have
not been included, but would be expected to increase risk concerns. Lifetime cancer risk
is estimated using the exposure and cancer potency factor (Qi*) and is expressed as a
probability of developing cancer. Cancer risks greater than one-in-a-million (1 x 10"6)
exceed OPP's level of concern.
a. Organic Arsenic Dietary Exposure and Risk
To estimate organic arsenic dietary exposure, EPA made the conservative
assumption that 100% of the exposure could be to organic arsenic. These estimates may
overestimate organic arsenic exposure and risk because the exposure is known to be to a
combination of organic and inorganic arsenic compounds.
Additionally, the Food Quality Protection Act of 1996 requires EPA to consider
the dietary exposure from all sources of a pesticide or, in this case, organic arsenic. "All
sources of organic arsenic" includes background (naturally occurring) levels of organic
arsenic in food and drinking water that are not necessarily resulting from the pesticidal
uses. To assess dietary exposure resulting from the pesticidal uses only, as well as to
consider all sources of organic arsenic that contribute to dietary exposure, EPA
performed three levels of dietary analyses using field trial data, modeled drinking water
exposure estimates, and the US Food and Drug Administration (FDA) Total Diet Study
(TDS). Level 1 most likely represents residues in food and water as a result of organic
arsenical herbicide applications. The Level 2 and Level 3 analyses include increasingly
broad exposure assumptions and were used to estimate aggregate dietary exposure to
arsenic from all potential sources.
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Level 1: Pesticide applications only (no background)
The level 1 acute and chronic dietary exposure analyses include cottonseed, the
only registered food commodity (residue estimates from field trial data), and two
different water scenarios reflecting uses on cotton and on turf. All residues are
considered to be either MMA or DMA.
Level 2: Pesticide applications plus residues in meat and fish
The level 2 acute and chronic dietary exposure analyses include: a) cottonseed and
meat (residue estimates from FDA TDS); b) cottonseed, meat, and two different
water scenarios; c) cottonseed, meat, and fish (residue estimates from FDA TDS);
and, d) cottonseed, meat, fish, and two different water scenarios. All residues are
considered to be either MMA or DMA.
Level 3: Pesticide applications plus background arsenic levels in food
The level 3 acute and chronic dietary exposure analyses include: a) cottonseed and
all commodities that were tested in the FDA TDS; b) cottonseed, all commodities
that were tested in the FDA TDS (e.g., cooked rice, cereal) and two different water
scenarios; c) cottonseed, all commodities that were tested in the FDA TDS, as well
as all commodities to which those data could be translated; and, d) cottonseed, all
commodities that were tested in the FDA TDS, all translated commodities, and two
different water scenarios. All residues are considered to be either MMA or DMA.
This document includes only the results of the Level 3 analysis because it
represents a very conservative "worst-case" dietary exposure scenario and the estimated
risks do not exceed EPA's level of concern. Results of the Level 1 and Level 2 analyses
are available at http://www.regulations.gov in docket number EPA-HQ-OPP-2006-0201.
i. MMA Acute and Chronic Dietary Risk
The acute and chronic results of the Level 3 dietary analyses are presented in
Table 9 and Table 10, respectively, and assume 100% of the total arsenic concentration is
MMA. The acute dietary risk estimates at the 99.9th percentile for food and water
aggregate exposure to MMA are below EPA's level of concern for the U.S. population
and all population subgroups. Results of the Level 1 and Level 2 analyses are not
presented in this document because the Level 3 analysis presents a "worst-case" scenario
and still does not exceed EPA's level of concern.
Table 9. Summary of MMA Level 3 Acute Dietary Risk
Population
Subgroup
U.S. Population
All Infants (<1 yr.)
Children 1-2 yrs.
Food only
Exposure
(mg/kg/day)
0.036201
0.028218
0.067527
%aPAD
36.2
29.2
67.5
Food + Cotton Water
Exposure
(mg/kg/day)
0.036779
0.031956
0.068276
%aPAD
36.8
31.2
68.3
Food + Turf Water
Exposure
(mg/kg/day)
0.047609
0.089358
0.073761
%aPAD
47.6
89.4
73.8
Page 24 of 46
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Table 10. Summary of MMA Level 3 Chronic Dietary Risk
Population
Subgroup
U.S. Population
All Infants (<1 yr.)
Children 1-2 yrs.
Food only
Exposure
(mg/kg/day)
0.000795
0.000611
0.001828
% cPAD
2.6
2.0
6.1
Food + Cotton Water
Exposure
(mg/kg/day)
0.001027
0.001371
0.002172
% cPAD
3.4
4.6
7.2
Food + Turf Water
Exposure
(mg/kg/day)
0.003493
0.009456
0.005835
% cPAD
11.6
31.5
19.4
ii. DMA Acute and Chronic Dietary Risk
The acute and chronic results of the Level 3 analyses are presented in Table 11
and Table 12, respectively, and assume 100% of the total arsenic concentration is DMA.
The acute dietary risk estimates at the 99.9th percentile for food and water aggregate
exposure to DMA are below EPA's level of concern for the U.S. population and all
population subgroups. Results of the Level 1 and Level 2 analyses are not presented in
this document because the Level 3 analysis presents a "worst-case" scenario and does not
exceed EPA's level of concern.
Table 11. Summary of DMA Level 3 Acute Dietary Risk
Population
Subgroup
U.S. Population
Children 1-2 yrs.
Food only
Exposure
(mg/kg/day)
0.036201
0.067527
%aPAD
30.2
56.3
Food + Cotton Water
Exposure
(mg/kg/day)
0.036537
0.067877
% aPAD
30.4
56.6
Food -I- Turf Water
Exposure
(mg/kg/day)
0.038003
0.069642
%aPAD
31.7
58.0
Table 12. Summary of DMA Level 3 Chronic Dietary Risk
Population
Subgroup
U.S. Population
All Infants (<1 yr.)
Children 1-2 yrs.
Food only
Exposure
(mg/kg/day)
0.000795
0.000611
0.001828
% cPAD
5.7
4.4
13.1
Food + Cotton Water
Exposure
(mg/kg/day)
0.000942
0.001094
0.002047
% cPAD
6.7
7.8
14.6
Food + Turf Water
Exposure
(mg/kg/day)
0.001764
0.003790
0.003268
% ePAD
12.6
27.1
23.3
b. Inorganic Arsenic Dietary Risk
To estimate inorganic arsenic dietary exposure, EPA made the conservative
assumption that 100% of the exposure could be to inorganic arsenic. These estimates
may overestimate inorganic arsenic exposure and risk because the exposure is known to
Page 25 of 46
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be to a combination of organic and inorganic arsenic compounds; however, limited
monitoring data in areas with high organic arsenical herbicide use appear to support a
relatively high level of transformation and thus confirm EPA's risk conclusions.
EPA estimated dietary risk to inorganic arsenic resulting from the organic
arsenical herbicide uses based on estimated drinking water exposure alone (i.e., without
food or background levels of arsenic). Cancer risk was calculated based on potential long
term EDWCs predicted using surface water modeling and using EPA's Qi* for inorganic
arsenic. The resulting dietary exposure exceeds OPP's 1 x 10"6 excess cancer risk (Table
13). EPA did not combine the EDWCs with food exposure because the risks posed by
EDWCs alone are above the LOG and further combination would result in increased risk
estimates that would further exceed the LOG.
Table 13. Inorganic Arsenic Surface Water EDWCs and Corresponding Cancer Risks
COTTON
Total Arsenic
Cancer EDWC
3.9ppb
Cancer Risk
3 x 10'4
TURF
Total Arsenic
Cancer EDWC
40.3 ppb
Cancer Risk
3 x 10"3
Note: OPP's target cancer risk is 1 x 10" equivalent to 0.02 ppb of inorganic arsenic
The modeled surface water EDWCs are intended to provide high end estimates of
potential drinking water exposure, representing exposure that might be expected in worst-
case scenarios when maximum labeled rates are applied in the most vulnerable sites.
This exposure may not have widespread occurrence nationally, depending on the extent
of vulnerability. Additional conservative assumptions are included in modeling exposure
from the turf use, leading to turf EDWCs that may be overestimated to some degree,
although the extent of overestimation cannot be quantified. Although there are
uncertainties in the modeling, available monitoring data support the conclusion that
typical use of organic arsenicals may result in drinking water exposure to inorganic
arsenic that exceeds levels of concern.
For surface water, a US Geological Survey study at river sites downstream of high
cotton use areas in Mississippi monitored for organic and inorganic arsenic, finding both
at concentrations up to 5 ppb. These detections are higher than background levels in the
study area which are not expected to exceed 2 ppb for total arsenic, with limited natural
contribution to organic arsenic levels.
Several monitoring studies in Florida golf course ponds found total arsenic
concentrations in individual samples of up to 120 ppb with annual means at individual
ponds of up to 64 ppb. Background arsenic in Florida surface water is expected to be <2
ppb. One of these studies speciated the total arsenic detections and found that in all but a
few samples, inorganic arsenic was dominant, representing more than 60% of the total
arsenic in most cases with many samples made up entirely of inorganic arsenic. This
indicates that significant transformation of organic arsenic to inorganic arsenic had
occurred. While these concentrations are not directly comparable to levels of exposure in
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drinking water, they demonstrate that organic arsenical herbicide applications can result
in substantial transport of organic and inorganic arsenic to surface water.
Groundwater may also be susceptible to arsenic contamination through leaching
of applied organic arsenical herbicides. Areas with shallow water tables, well drained
soils, and low background arsenic levels are particularly vulnerable to impacts from
organic arsenical herbicide use. Although modeling of potential groundwater exposure
was not conducted, available monitoring data show that in these environments,
groundwater may be impacted by organic arsenical use. In Florida, a vulnerable
environment, 90% of the state's drinking water comes from groundwater. From 2003 to
2005, at least 5% of Florida drinking water compliance monitoring samples exceeded 3
ppb arsenic with detections as high as 240 ppb. These detections are not directly linked
to organic arsenical herbicide use, but they exceed typical background values and are
likely impacted by some kind of anthropogenic input (e.g., organic arsenical herbicides).
Monitoring in shallow wells beneath golf courses detected arsenic in groundwater at 9 of
14 Florida golf courses tested, with detections of up to 120 ppb in shallow wells (<12 ft
depth) and up to 11 ppb in deeper wells (<28 ft depth).
Considering both the modeling results and the monitoring data, the weight of the
evidence supports EPA's conclusion that use of organic arsenical herbicides may lead to
exposure to inorganic arsenic in drinking water that exceeds levels of concern for excess
cancer risk.
3. Residential Exposure and Risk
a. Organic Arsenic Residential Risk
MSMA, DSMA, CAMA, and cacodylic acid are currently registered for use in
residential settings. Non-cancer risk estimates (such as residential estimates) are
expressed as a margin of exposure (MOE) which is a ratio of the dose from a
toxicological study selected for risk assessment, typically a NOAEL, to the predicted
exposure. Estimated MOEs are compared to a level of concern which reflects the dose
selected for risk assessment and uncertainty factors (UF) applied to that dose. The
standard UF is lOOx, which includes lOx for interspecies extrapolation (to account for
differences between laboratory animals and humans) and lOx for intraspecies variation
(to account for differences within the same species). Additional uncertainty or safety
factors may also be applied.
There are potential exposures to residential handlers (mixers, loaders, and
applicators) during the usual use-patterns associated with MSMA, DSMA, CAMA, and
cacodylic acid. All risks for residential handlers are below EPA's level of concern (MOE
140 to 29,000 for dermal; MOE 4,700 to 320,000 for inhalation).
There are potential exposures to individuals in residential settings following
application of MSMA, DSMA, CAMA, and cacodylic acid. The following
postapplication scenarios were identified:
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• dermal exposure from residues on lawns (adult and toddler);
• hand-to-mouth transfer of residues on lawns (toddler);
• ingestion of pesticide residue on treated grass (toddler); and
• incidental ingestion of soil from pesticide-treated residential areas (toddler).
There are potential postapplication risks of concern for MSMA, DSMA, CAMA,
and cacodylic acid as they are currently used in residential settings. The target level of
concern for DMA incidental oral scenarios is 30 (i.e., MOE > 30 is not of concern).
Table 14 presents the short-term incidental oral MOEs for DMA for toddlers that are <30
for the hand-to-mouth activity and object-to-mouth activities on turf.
Table 14. Toddler Residential Risks of Concern for Postapplication Exposure to DMA
Exposure Scenario
Hand to Mouth Activity on Turf
Object to Mouth Activity on Turf
Route of
Exposure
Oral
Formulation
Spray
Application Rate
(Ib ai/A)
7.72
7.3
7.72
7.3
MOE-
DayO
4
4
15
16
b. Inorganic Arsenic Residential Risk
The estimated residential exposure to inorganic arsenic is small compared to the
estimated exposure in drinking water. EPA believes the residential exposure would
primarily be to organic arsenic during application or shortly after application.
Transformation of the organic arsenic to inorganic arsenic would occur over time and
buildup in soil of the inorganic form is possible. Although inorganic arsenic levels in soil
may increase, exposure over time would be low since the inorganic material would be
below the soil surface and not be readily available for exposure. The main route of
exposure to inorganic arsenic would be thru the ingestion of treated soil, but EPA does
not believe this is a major route of long term exposure. EPA did not combine the
EDWCs with food or residential exposure because the risks posed by EDWCs alone are
above the LOG and further combination would result in increased risk estimates that
would further exceed the LOG.
4. Aggregate Risk
In reassessing tolerances, FFDCA Section 408(b)(2)(A)(ii) requires EPA to
examine the "aggregate exposure to the pesticide chemical residue, including all
anticipated dietary exposure and other exposures for which there is reliable information."
An aggregate risk assessment considers the combined risk from dietary exposure (food
and drinking water) as well as exposure from non-occupational sources (residential uses).
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a. Acute Aggregate Risk for Organic Arsenic
Acute aggregate exposures (less than one day) may result from consuming treated
food or drinking water. Acute aggregate exposures may also result from residential
exposures such as adults doing yard work or playing golf on treated turf, or from children
playing on treated turf. Typically EPA does not aggregate acute dietary exposures with
acute residential exposures because it is very unlikely that high-end food and water
exposures will occur on the same day as the maximum residential exposures. Therefore,
acute aggregate risks for MMA and DMA are considered to represent the acute dietary
risks. As noted above, the acute dietary risk estimates for the U.S. population and all
subgroups are well below EPA's level of concern. The most highly exposed subgroup
for MMA is all infants (<1 yr.) at 89.4% of the aPAD and the most highly exposed
subgroup for DMA is children 1-2 at 58.0% of the aPAD.
b. Short-Term Aggregate Risk for Organic Arsenic
Aggregate short-term risk estimates include the contribution to risk from chronic
dietary sources (food + water) and short-term residential or recreational sources. Though
estimated aggregate chronic (long-term) dietary risks are not of concern, short-term
residential exposures alone pose potential risks of concern to toddlers from
postapplication exposures to DMA and CAMA. EPA did not aggregate residential
exposure with dietary exposure because the risks posed by residential exposure alone are
above the LOG and further aggregation would result in increased risk estimates that
would further exceed the LOG. Residential risks from CAMA could likely be addressed
through mitigation (e.g., relatively small rate reductions). However, risks from DMA
would necessitate much more extensive mitigation.
EPA combines risk values resulting from separate residential postapplication
exposure scenarios when it is likely they can occur simultaneously based on the use-
pattern and the behavior associated with the exposed population. The combined MOEs
for MSMA and DSMA do not exceed EPA's level of concern; the combined MOEs for
CAMA at the 4.4 Ibs. ai/A rate and cacodylic acid at the 7.3 and 7.7 Ibs. ai/A rates exceed
EPA's level of concern and are presented in Table 15 and Table 16, respectively.
Table 15. Combined MOE Estimates for CAMA
Postapplication Exposure Scenario
Margins of Exposure (MOEs)
(UF=100)
Short-Term
(Non-Dietary)
Total Non-
Dietary Risk
Turf
Toddler
Turf
(4.4 Ib ai/acre)
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
110
430
32,000
85
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Postapplication Exposure Scenario
Turf
(3.7 Ib ai/acre)
Turf
(2.2 Ib ai/acre)
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Margins of Exposure (MOEs)
(UF=100)
Short-Term
(Non-Dietary)
130
510
38,000
210
850
64,000
Total Non-
Dietary Risk
101
170
Table 16. Combined Toddler MOE Estimates for DMA
Postapplication Exposure Scenario
Margins of Exposure (MOEs)
(UF=30)
Short-Term
(Non-Dietary)
Total Non-
Dietary Risk
Turf
Toddler
Turf
(7.72 Ib ai/acre)
Turf
(7.3 Ib ai/acre)
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
Hand to Mouth
Object to Mouth
Incidental Soil
Ingestion
4
15
1,100
4
16
1,200
3
3
c. Intermediate-Term Aggregate Risk for Organic Arsenic
All residential/recreational exposures are expected to be short-term in duration;
therefore, no intermediate-term aggregate analysis was performed.
d. Long-Term Aggregate Risk for Organic Arsenic
Long-term (noncancer) aggregate risk estimates include the contribution of risk
from chronic dietary sources (food + water) and residential sources. However, based on
the labeled uses, no long-term or chronic residential exposures are expected. Chronic
risk estimates from exposures to food alone do not exceed EPA's level of concern for any
exposed population or subgroup based on conservative estimates of exposure. As in the
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acute aggregate assessment, chronic surface water EDWCs were calculated to estimate
the potential contribution to the chronic exposure from drinking water, and the EDWCs
were combined with chronic food exposures to estimate potential long-term aggregate
risks from the uses of DMA and MMA. Aggregate chronic dietary exposure did not
exceed EPA's level of concern for MMA (32% of the cPAD for the highest exposed
subgroup, infants <1 yr.) or DMA (27% of the cPAD for the highest exposed subgroup,
infants <1 yr.).
e. Aggregate Cancer Risk for Organic Arsenic
MMA is classified as "no evidence for carcinogenicity," based on the lack of
evidence of carcinogenicity in acceptable studies in rats and mice. DMA is classified as
"not carcinogenic up to doses resulting in regenerative proliferation," therefore a cancer
dietary analysis was not warranted and was not performed.
f. Aggregate Cancer Risk for Inorganic Arsenic
Inorganic arsenic is classified as a "known human carcinogen;" therefore, a
cancer assessment was performed. EPA estimated dietary cancer risk to inorganic
arsenic resulting from the organic arsenical herbicide uses by calculating the estimated
drinking water exposure alone (i.e., without food or background levels of arsenic) using
EPA's cancer potency factor (Qi*) for inorganic arsenic. The resulting dietary exposure
exceeds OPP's 1 x 10"6 excess cancer risk (3 x 10"3 for turf uses). EPA did not aggregate
the EDWCs with food, residential, or background exposure because the risks posed by
EDWCs alone are above the LOG and further aggregation would result in increased risk
estimates that would further exceed the LOG.
5. Cumulative Risk Assessment
Risks summarized in this document are those that result only from the use of the
organic arsenical herbicides. The Food Quality Protection Act (FQPA) requires that, when
considering whether to establish, modify, or revoke a tolerance, the Agency consider
"available information" concerning the cumulative effects of a particular pesticide's
residues and "other substances that have a common mechanism of toxicity." Unlike other
pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to
the organic arsenical herbicides. EPA has not assumed that the organic arsenical herbicides
share a common mechanism of toxicity with other compounds. For information regarding
EPA's efforts to determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the policy statements released by
EPA's Office of Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common mechanism of
toxicity on EPA's website at http://www.epa.gov/pesticides/cumulative/.
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6. Occupational Risk
a. Organic Arsenic Occupational Risk
Workers can be exposed to MSMA, DSMA, CAMA, or cacodylic acid by mixing,
loading, or applying or by entering a previously treated site. Like residential risk, worker
risk is measured by MOEs. For handlers, EPA initially assesses risk at "baseline" which
considers normal work clothing (i.e., long sleeve shirt and long pants), no gloves, and no
respirator. If there is a concern at baseline, EPA considers the use of protective measures
(e.g., personal protective equipment) to lower the risk. Personal protective equipment
(PPE) can include an additional layer of clothing, chemical-resistant gloves, and/or a
respirator.
i. Organic Arsenic Occupational Handler Risk
Occupational handlers can be exposed to MMA or DMA by mixing, loading, or
applying MSMA, DSMA, CAMA, or cacodylic acid.
For inhalation exposure, all scenarios for MSMA, DSMA, and CAMA do not
exceed EPA's level of concern at baseline. For dermal exposure, several scenarios
exceed EPA's level of concern for MSMA (MOEs = 12 to 89), DSMA (MOEs = 12 to
90), and CAMA (MOEs = 55 to 66) at baseline. All scenarios are below EPA's level of
concern at baseline plus gloves (MOEs = 580 to 66,000).
For inhalation exposure, all scenarios for cacodylic acid do not exceed EPA's
level of concern at baseline. For dermal exposure, several scenarios exceed EPA's level
of concern for cacodylic acid (MOEs = 7.5 to 56). All but one scenario (MOE = 92) was
below EPA's level of concern at baseline plus gloves (MOEs = 580 to 66,000).
ii. Organic Arsenic Occupational Postapplication Risk
Workers can be exposed to MMA or DMA by being in an environment that has
been previously treated with MSMA, DSMA, CAMA, or cacodylic acid.
For inhalation and dermal exposures, all scenarios for MSMA, DSMA, and
CAMA do not exceed EPA's level of concern at baseline assuming workers do not enter
before the 12-hour restricted entry interval (REI).
For inhalation exposures, all scenarios for cacodylic acid do not exceed EPA's
level of concern at baseline assuming workers do not enter before the 12-hour REI. For
dermal exposures, several scenarios for cacodylic acid exceed EPA's level of concern at
baseline as presented in Table 17. Post application risk would likely be of greatest
concern for workers on sodfarms and could be addressed with longer REIs.
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Table 17. Postapplication Worker Risks of Concern for Cacodylic Acid
Crop Grouping
Turf
Application rate
(Ib ai/acre)
7.7
7.3
Transfer Coefficient
3400
6800
3400
6800
Day after
Application
when MOE
>100
8
14
7
13
MOE at Day 0
45
22
47
24
b. Inorganic Arsenic Occupational Risk
Mixers and loaders, and most post-application workers would only be exposed to
organic arsenic. The estimated occupational exposure to inorganic arsenic from
application of MSMA, DSMA, CAMA or cacodylic acid products is insignificant. Thus,
no quantitative estimate has been completed.
7. Incident Reports
There are reported MSMA and DSMA incidents involving adults and children,
several of which resulted in hospitalization. Some reports described symptoms such as
dizziness, sinusitis, rhinitis, memory loss, numbness, tingling, rash, and fever, after aerial
applications, but many were non-specific about the source of exposure. Other reports
described effects such as systemic allergic symptoms, nausea, dizziness, and eye irritation
for both agricultural and non-agricultural uses. From the limited information available,
systemic allergic reactions and eye irritation are the most common types of effects seen.
EPA had no reported incidents for CAMA.
There are reported cacodylic acid incidents involving children < 6 years of age,
but none resulted in hospitalization. No other information, such as the activity associated
with the exposure, was reported. Incidents reported for adults involved both agricultural
and non-agricultural uses and included skin and eye irritation, respiratory effects, and
systemic effects. The incidents resulted in absences from work and, in a few cases,
hospitalization. Incidents were associated with use on lawn, turf, ornamentals, and cotton.
C.
Environmental Risk Assessment
EPA has conducted an environmental risk assessment for the organic arsenical
herbicides to support the reregistration eligibility decision. EPA evaluated the submitted
environmental fate and ecological studies as well as available open literature and
determined that the data are adequate to support a reregistration eligibility decision. A
summary of the environmental risk assessment findings and conclusions is provided
below; the full risk assessments are available at http://www.regulations.gov in docket
number EPA-HQ-OPP-2006-0201.
Page 3 3 of 46
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1. Environmental Fate and Transport
Unlike other pesticides that degrade over time, MSMA, DSMA, CAMA, and
cacodylic acid contain the element arsenic which does not degrade. Arsenic can,
however, transform (i.e., change forms) or be redistributed through runoff, leaching,
erosion, volatilization, or plant uptake. The extent and speed of transformation and
redistribution of the organic arsenical herbicides in soil is highly variable and depends
mostly on localized environmental conditions. Thus, persistence of applied organic
arsenical herbicides can range from days to years, depending on soil properties and
ambient conditions such as soil moisture, temperature, chemical concentration, bacterial
population, and amount of organic matter.
Although the environmental fate of the organic herbicides is highly variable
depending on localized environmental conditions, environmental fate laboratory studies
show that organic arsenicals are stable under all tested abiotic conditions; they do not
degrade by hydrolysis or by aquatic or soil photolysis. Metabolism rates do not appear to
depend linearly on arsenical concentration; the kinetics are therefore not necessarily first-
order and so "half-life" may not be an appropriate constant for all concentrations.
Despite the uncertainty, first-order half-lives have been calculated for modeling purposes.
The estimated half-lives used in the risk assessments may underestimate the faster initial
rate of metabolism but adequately portray the overall transformation and so are assumed
to be protective for chronic exposure, a major concern for arsenicals.
The modeled aerobic and anaerobic soil half-lives for MMA and DMA are
presented in Table 18. The modeled aerobic soil half-life for MMA is 240 days; no
anaerobic soil half-life was determined. The modeled aerobic soil half-life for DMA is
173 ± 115 days with a standard upper 90% confidence limit on the mean of 240 days.
The anaerobic soil half-life for DMA was calculated to be 128 ± 38 days with a standard
upper 90% confidence limit on the mean of 168 days.
Table 18. Soil Half-Lives for MMA and DMA used in EPA's Risk Assessments
Chemical
MMA
DMA
Aerobic Half-Life
240 days
173 ±115 days
Anaerobic Half-Life
ND
128 ± 38 days
ND = Not determined
The effects of environmental factors on the rate of arsenical metabolism are
complex and poorly defined, with different studies leading to conflicting results. An
increase in temperature leads to increased metabolism. The observed influences of soil
organic matter or applied arsenical concentrations are contradictory. The effect of
aerobic versus anaerobic conditions on metabolism rates is also ambiguous.
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a. Metabolites
Potential metabolites of applied organic arsenicals include volatile alkylarsines
and inorganic arsenic (as arsenate or arsenite) along with carbon dioxide. Additionally,
DMA may be present as a metabolite of MMA as well as applied directly. As with the
rate, the metabolism pathway is sensitive to environmental conditions in indeterminate
ways with the major metabolites occurring in widely variable proportions.
Transformation to volatile alkylarsines, the only metabolism route that would directly
reduce soil arsenic loading, has been shown to be possible in certain circumstances but is
generally not expected to be a major route of dissipation. A maximum of 35% of applied
MMA is expected to be present as DMA at any one time. Theoretically, there is some
possibility for MMA to metabolize to DMA, but significant transformation has not been
observed in current acceptable field or laboratory studies. Observed metabolism of
MMA and DMA to inorganic arsenic has ranged from undetected after several years to
more than 80% transformation in several months. Generally, arsenate [As(V)] is
expected to be the dominant species of inorganic arsenic, but in reducing conditions,
arsenite [As(III)] may be more stable.
Some of the variability in metabolism processes is associated with variability in sorption,
because microbial transformation is only likely to occur while compounds remain
dissolved in pore water. Mobility of arsenicals is typically very low to intermediate and
appears to be independent of organic matter content. Instead, sorption is higher in soils
with higher percentage of clay or with more iron or aluminum content. One study found
by direct comparison that all arsenicals were more strongly sorbed than phosphate in the
increasing order: phosphate < DMA < arsenate ~ MMA. The lowest non-sand Kd for
MMA is 11.4 mL/g. For 20 tested soils, the range of KdS spans two orders of magnitude
(0.5 to 95 mL/g, mean 37 mL/g). For DMA, the lowest non-sand Kd from 16 soils is 8.2
mL/g (range 8.2 to 33 mL/g, mean 18 mL/g).
b. Surface Water Exposure Conclusions
Arsenical pesticides and their metabolites may be transported to surface waters
and sediments through runoff water, eroding soils, or drift during application. These
routes of exposure are likely to lead to elevations above background arsenic levels in
surface water bodies. Tier I surface water modeling for MSMA and DSMA estimated
surface water concentrations in ponds and streams as high as 360 ppb, as MMA. Limited
targeted monitoring has found elevated total arsenic levels in surface water bodies in
MMA use areas. In cotton growing areas in Mississippi, surface water concentrations of
MMA up to 5 ppb were detected. In Florida, concentrations of up to 120 ppb have been
detected in golf course ponds.
c. Soil Accumulation Conclusions
The relative immobility of arsenicals along with arsenic's elemental nature make
buildup in soil after repeated applications an important consideration. Controlled field
studies, monitoring targeted to pesticide use areas, and soil modeling results all indicate
Page 3 5 of 46
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that soil buildup is a likely result of long term organic arsenical application. Arsenic
accumulation is likely to be limited to the top layers of soil, with studies suggesting that it
is unlikely to occur at depths greater than 30 cm.
2. Environmental Effects
a. Ecological Risk Estimation
EPA's ecological risk assessment compares toxicity endpoints from ecological
toxicity studies to estimated environmental concentrations (EECs) based on
environmental fate characteristics and pesticide use data. To evaluate the potential risk to
non-target organisms from the use of organic arsenic herbicide products, the Agency
calculated a Risk Quotient (RQ), which is the ratio of the EEC to the most sensitive
toxicity endpoint value, such as the median lethal dose (LD50) or the median lethal
concentration (LCso). These RQ values are then compared to EPA's level of concern
(LOG) indicating whether or not a pesticide, when used as labeled, has the potential to
cause adverse effects on non-target organisms. If an RQ exceeds the LOG, the risk may
be addressed through further refinements of the assessment or through mitigation. Use,
toxicity, fate, and exposure are considered when characterizing the risk, as well as the
levels of certainty and uncertainty in the assessment. EPA further characterizes
ecological risk based on any reported incidents to non-target terrestrial or aquatic
organisms in the field (e.g., fish or bird kills). Table 19 presents EPA's level of concern
for acute, acute endangered listed species, and chronic risk for terrestrial and aquatic
animals as well as plants.
Table 19. Target Levels of Concern for Ecological Risk Assessments
Risk Category
Acute Risk
Acute Endangered Listed Species
Chronic Risk
Terrestrial Animal
LOC
0.5
0.1
1
Aquatic Animal
LOC
0.5
0.05
1
Plant
LOC
1
1
Not Assessed
b. Aquatic Organism Risk
All calculated MMA and DMA RQs for fish and aquatic invertebrates are < 0.05
and below EPA's level of concern (LOC). All calculated MMA and DMA RQs for
aquatic plants are < 1 and below EPA's level of concern (LOC).
c. Terrestrial Organism Risk
Most of the terrestrial mammal acute RQs for exposure to MMA or DMA, except
those for granivores, exceeded the endangered species LOC of 0.1; some also exceeded
the restricted use LOC of 0.2 and high risk LOC of 0.5. These RQs are presented below
in Table 20 for MMA and Table 21 for DMA. All but 2 of the chronic RQs for MMA
exceeded the chronic risk LOC of 1. For DMA, chronic RQs were not calculated but
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there is evidence that chronic exposure may be toxic to some mammals, based on the
results of a developmental rabbit study in which the toxic threshold was below the
estimated exposure. These RQs are calculated based on mammals with body weights of
35 g that consume green vegetation or insects equivalent to 66% of their body weight
(herbivores and insectivores) or seeds equivalent to 15% of their body weight
(granivores).
Table 20. Risk Quotients for Small Mammals (35g) Exposed to MMA
Crop
(Chemical)
Cotton
Non-crop
Orchard
Turf; max
Turf; golf
Herbivore
0.17*
6.04***
0.48**
5.25***
3 50***
Acute RQs *
Inseetivore
0.10*
3 39***
0.27**
2 95***
I 97***
Granivore
<0.
<0.
<0.
<0.
<0.
Herbivore
7.3*
26*
21*
22*
15*
Chronic RQs3
Insectivore
4.1*
14*
12*
13*
8.3*
Granivore
0.46
1.6*
1.3*
1.4*
0.93
1 Acute RQ = EEC / LD50, corrected for body weight; LD50s = 1599 mg/kg (rat) for DSMA, 157 mg/kg
(rat) for MSMA, adjusted for purity of test material.
2 Chronic RQ = EEC/NOEC, corrected for body weight; NOEC = 100 ppm (rat) for MMA
*** exceeds LOCs for high risk (0.5), restricted use (0.2), and endangered species (0.1)
** exceeds the LOCs for restricted use and endangered species
exceeds the LOG for endangered species
t
exceeds the chronic risk LOG (1)
Table 21. Risk Quotients for Small Mammals (35g) Exposed to DMA
Crop
(Chemical)
Cotton
Noncrop
Areas
Orchards
(understory)
Acute RQs 1>2
Herbivore3
0.2**
1.6***
I 0***
Insectivore3
0.1*
I 9***
I 2***
Granivore4
<0.1
0.1
O.I
Chronic RQs
Herbivore Insectivore
Not quantified
Granivore
1 RQ = EEC / [LD50 / food eaten expressed as % of bw]
2 LD50 = 823 mg/kg (lab. rat)
3 for a 35-g herbivore or insectivore (mammal) that consumes an amount of green vegetation or insects
equivalent to 66% of its body weight
4 for a 35-g granivore (mammal) that consumes an amount of seeds equivalent to 15% of its body weight
*** exceeds LOCs for high risk (0.5), restricted use (0.2), and endangered species (0.1)
** exceeds the LOCs for restricted use and endangered species
* exceeds the LOG for endangered species
* exceeds the chronic risk LOG (1)
Acute RQs for birds exposed to MMA are presented below in Table 22. As with
terrestrial mammals, most RQs, with the exception of granivores, exceed the restricted
use and endangered species LOCs of 0.2 and 0.1 while some also exceed the high risk
LOG of 0.5. For DMA, minimal acute risk to birds is presumed. DMA is practically
non-toxic to birds and maximum residues on avian food items are not expected to exceed
levels of concern at any use site. Chronic RQs for birds exposed to MMA or DMA have
not been calculated due to lack of data.
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Table 22. Risk Quotients for Birds from Exposure to MMA
Crop
(Chemical)
Cotton
Non-crop
Orchard
Turf; max
Turf; golf
Acute RQ 1
Herbivores
0.16*
1.53***
0.54***
1.33***
0.89***
Insectivores
0.1
0.86***
0.30**
0.75***
0.50***
Granivores
0.1
0.1*
0.1
0.1
0.1
1 RQ = EEC /LC50; LC50s = 4695 mg/kg (DSMA) and 1667 mg/kg (MSMA), both for northern bobwhite,
adjusted for purity of the test material.
*** exceeds LOCs for high risk (0.5), restricted use (0.2), and endangered species (0.1)
** exceeds the LOCs for restricted use and endangered species
* exceeds the LOG for endangered species
d. Terrestrial and Semi-Aquatic Plants
Risk quotients for terrestrial and semi-aquatic plants exposed to drift and/or runoff
are summarized below in Table 23 for MMA and Table 24 for DMA. For MMA, most
RQs for endangered and non-endangered plants, both upland and semi-aquatic, exceed
the LOG of 1 for exposure from runoff and drift. None of the drift-only RQs exceed the
LOG. For DMA, no LOCs are exceeded for the use on cotton. The DMA non-crop and
orchard uses exceed the LOG for endangered and non-endangered semi-aquatic plants
Table 23. Risk Quotients for Terrestrial and Semi-Aquatic Plants from Exposure to
DSMA or MSMA
Crop
(Chemical)
Cotton
Non-crop
Orchard
Turf; golf
Turf; max
Non-Endangered RQs *
Upland3
<1
2*
<1
1.7*
1.1*
Semi-
Aquatic3
<1
17*
1.5*
15*
9.8*
Drift Only
<1
<1
<1
<1
<1
Endangered RQs 2
Upland3
<1
13*
<1
11*
7.4*
Semi-
Aquatic3
3*
109*
6*
95*
63*
Drift Only
<1
<1
<1
<1
<1
1 RQ = EEC / EC25. For total loading use seedling emergence EC25 (1.25 and 0.116 Ib ai/A for DSMA
and MSMA, respectively). For drift use vegetative vigor EC25 (0.354 and 0.418 Ib ai/A for DSMA and
MSMA, respectively)
2 RQ = EEC / NOEC. For total loading use seedling emergence NOEC (0.30 and 0.018 Ib ai/A for DSMA
and MSMA, respectively). For drift use vegetative vigor NOEC (O.30 and 0.14 Ib ai/A for DSMA and
MSMA, respectively)
3 Upland EEC based on sheet runoff + drift; Semi-Aquatic EEC based on channelized runoff + drift.
* exceeds the LOG (RQ >1) for nontarget plants
Table 24. Risk Quotients for Terrestrial and Semi-Aquatic Plants from Exposure to
DMA
Crop
(Chemical)
Cotton
Non-Endangered RQs 1
Upland3
<1
Semi-
Aquatic3
<1
Drift Only
<1
Endangered RQs 2
Upland3
<1
Semi-
Aquatic3
<1
Drift Only
<1
Page 3 8 of 46
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Noncrop
Orchard
<1
<1
4.5*
2.8*
<1
<1
<1
<1
6.2*
3.8*
2.7*
1.7*
1 RQ = EEC / EC25. For total loading use seedling emergence EC25 (0.92 Ib ai/A). For drift use
vegetative vigor EC25 (0.12 Ib ai/A)
2 RQ = EEC / NOEC. For total loading use seedling emergence NOEC (0.67 Ib ai/A). For drift use
vegetative vigor NOEC (0.03 Ib ai/A)
3 Upland EEC based on sheet runoff + drift; Semi-Aquatic EEC based on channelized runoff + drift.
* exceeds the LOG (RQ >1) for nontarget plants
3. Ecological Incidents
The Ecological Incident Information System database included several ecological
incidents possibly related to use of organic arsenicals. The majority of these incidents
involved damage to treated plants, both turf and cotton (MSMA - 4 incidents; DSMA - 2
incidents; CAMA - 11 incidents). The certainty that these incidents were the result of
organic arsenical herbicide use was rated "possible" in all of these incidents but one,
which was rated "probable." Other ecological incidents included two reports of damage
to nearby vegetable plants from treatment of rights-of-way with MSMA. Additionally,
there was one report of a dead bird found after treatment with cacodylic acid and one
reported fish kill in a canal receiving runoff from golf courses treated with MSMA. In all
of these incidents, the certainty that the effects were the result of use of arsenicals was
rated "possible."
4. Endangered Species Risk
EPA's screening level assessment predicts that the organic arsenical herbicides
will have no direct acute effects on threatened and endangered aquatic organisms. The
risk assessments also indicate that RQs exceed endangered species LOCs for endangered
terrestrial animals and plants. Further, potential indirect effects to any species, dependent
upon a species that experiences effects from use of organic arsenical herbicides, cannot
be precluded based on the screening level ecological risk assessment. These findings are
based solely on EPA's screening level assessment and do not constitute "may affect"
findings under the Endangered Species Act.
IV. Risk Management, Reregistration, and Tolerance Reassessment Decisions
A. Public Comments and Responses
Through EPA's public participation process, EPA worked extensively with
stakeholders and the public to reach the regulatory decisions for MSMA, DSMA,
CAMA, and cacodylic acid. During the public comment period on the risk assessments,
which closed on June 5, 2006, the Agency received ten comments from the following
respondents: MAATF, Scotts Company, Florida Department of Environmental Protection
(DEP), Florida Department of Agriculture and Consumer Services (DACS), Golf Course
Superintendents Association of America (GCSAA), Wood Preservative Science Council
(WPSC), and two individuals. The MAATF's comments presented alternative
approaches to assessing environmental fate and dietary exposure. Florida DEP and
DACS's comments emphasized the need for a better understating of the environmental
Page 3 9 of 46
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fate and transport of the organic arsenical herbicides, especially in areas like Florida
where a large amount of drinking water comes from ground water. GCSAA's comments
supported the continued use of organic arsenical herbicides to support efficacious and
cost-effective weed control. WPSC's comments presented an alternative way to assess
background levels of arsenic. One individual's comments included two posters presented
by the Canadian Wildlife Service. The other individual's comment expressed a concern
of continued use of organic arsenical herbicides on athletic fields. Additional public
comments received after the comment period included several submissions of two form
letters supporting the reregi strati on of MSMA and DSMA. All comments and EPA's
official responses are available at http://www.regulations.gov in docket number EPA-
HQ-OPP-2006-0201.
B. Benefits and Alternatives
As part of the reregi strati on eligibility determination, EPA assessed the benefits
and alternatives for each organic arsenical herbicide use. In general, EPA finds only
limited benefits associated with the use of MSMA, DSMA, CAMA, and cacodylic acid,
based on steadily declining use and the availability of effective alternatives. A summary
of alternatives assessment findings and conclusions is provided below; the full
alternatives assessment for major uses of these chemicals is available at
http://www.regulations.gov in docket number EPA-HQ-OPP-2006-0201.
1. Cotton
Use in cotton has steadily declined since the late-1990s as alternative weed
control strategies (e.g., Round-up® ready cotton) have become more prevalent.
Additionally, EPA estimates that approximately no more than 6% of all cotton grown in
the US is treated with MSMA or DSMA. Cacodylic acid shows little use in the US in
recent years. DSMA and MSMA are used as post-emergent weed control, and cacodylic
acid is used as a pre-plant burn down weed control and as a cotton harvest aid
(desiccant/defoliant). For weed control, in addition to glyphosate (Round-up®)
alternatives include diuron, norflurazon, pendimethalin, trifluralin, fluazifop and
halosulfuron-methyl among others, depending on timing of application and the weed
complex that needs to be controlled. For the harvest-aid use of cacodylic acid,
alternatives include ethephon, dimethipin, thidiazuron and sodium chlorate, among
others. EPA estimates that the impact of using alternatives is a decrease in net cash
return to growers of approximately 6%. Because use has steadily declined, the current
per cent of crop treated is small, alternatives are readily available for the sub-set of
growers who use arsenicals, and the impact on net revenues from switching to these
alternatives is relatively small, EPA concludes that the benefits of organic arsenical
herbicide use on cotton are not compelling in light of the possible cancer risk from
drinking water contamination.
Page 40 of 46
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2. Turf
Turf uses for the organic arsenical herbicides include grasses grown for seed,
lawns, ornamental turf, sod farms, turfgrass, and turf grown for sod. Many alternatives
exist to control weeds on turf including fluazifop and dithiopyr for postemergence control
and dithiopyr or pendimethlin for preemergent control of crabgrass. The primary manner
in which grass weeds such as crabgrass and dallisgrass can be effectively controlled is
through the maintenance of a high quality turf such as is the case in almost all golf
courses. However, when chemical control of grass weeds is needed, typically, two or
more alternative chemicals would be required to achieve weed control comparable to the
organic arsenicals. Preemergence products are typically highly effective at controlling
crabgrass seedlings. However, the post emergent alternatives for the organic arsenical
herbicides either control a narrow spectrum of weeds, or they are not effective on the
more difficult grass weeds like dallisgrass (Paspalum dilatatum). Thus, multiple
herbicides used in combination can be considered an alternative to the organic arsenical
herbicides, but no single herbicide can be considered a direct replacement. Alternatives
vary in price from slightly less expensive to considerably more expensive than the
organic arsenicals.
Because there are both chemical and non-chemical alternatives available and any
additional costs of using the alternatives will be borne by those using and benefiting from
the improved turf, EPA concludes that the benefits of organic arsenical herbicide use on
turf are not compelling in light of the possible cancer risk to the general population from
drinking water contamination due to the use of these compounds.
3. Other Uses
Relatively small amounts of the organic arsenical herbicides are also used in
nonbearing orchards and vineyards, noncrop areas, ornamentals, and nonbearing citrus.
Similar to cotton, the organic arsenical herbicides are used for generalized weed control
in these areas. Similar to weed control in cotton, comparable efficacy in these areas can
likely be achieved through a combination of agents. In addition, EPA's Screening Level
and Usage Analysis indicate that use in these areas are minimal compared to cotton and
turf uses. Because the use is relatively small and alternatives are readily available, the
benefits of retaining organic arsenical herbicide use on nonbearing orchards and
vineyards, noncrop areas, ornamentals, and nonbearing citrus are thought to be limited.
C. Determination of Reregistration Eligibility and Regulatory Rationale
1. Reregistration Eligibility Decision
Section 4(g)(2)(A) of FIFRA calls for EPA to determine, after submission of relevant
data concerning an active ingredient, whether or not products containing the active
ingredient are eligible for reregi strati on. EPA has previously identified and required the
submission of the generic (i.e., active ingredient-specific) data required to support
reregi strati on of products containing MSMA, DSMA, CAMA, or cacodylic acid as an
Page 41 of 46
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active ingredient. The Agency has reviewed these generic data, and has determined that
the data are sufficient to support a reregi strati on eligibility decision for all products
containing MSMA, DSMA, CAMA, or cacodylic acid. EPA considered the available
information and has concluded that all currently registered uses of MSMA, DSMA,
CAMA, and cacodylic acid are not eligible for reregi strati on. This conclusion is based on
EPA's finding of limited benefits, adequate alternatives, and drinking water cancer risk
exceeding the Agency' s level of concern. EPA concludes that the risks of continued use
on all sites outweigh the limited benefits of weed control.
2. Regulatory Rationale for EPA's Reregistration Eligibility Decision
EPA's decision under FIFRA is based on a thorough evaluation of both the risks
and benefits of the uses of the organic arsenical herbicides. The Agency's primary
concern is the potential for applied organic arsenical products to transform to a more
toxic inorganic form of arsenic in soil with subsequent transport to drinking water. In
addition, EPA also identified some risk associated with the direct use of the organic
arsenical herbicides.
Dietary exposure from drinking water alone results in risks that exceed OPP's
level of concern for excess cancer risk (1 x 10"6). Estimated drinking water
concentrations for turf result in an excess cancer risk of 3 x 10"3. EDWCs for cotton
result in an excess cancer risk of 3 x 10"4. These risk conclusions are supported by
limited monitoring data in areas with high organic arsenical herbicide use. In addition,
occupational handler dermal MOEs exceed LOCs; postapplication worker dermal MOEs
exceed LOG; residential oral postapplication MOEs exceed LOG for CAMA and
cacodylic acid; and ecological risk quotients exceed LOCs.
EPA explored potential mitigation measures to reduce exposure and risk. EPA
met with the technical registrants to explore the possibility of labeling changes to reduce
risks while preserving the efficacy and usability of the active ingredients and associated
end-use products. The following labeling change options were considered:
• Limit golf course use to tees, fairways, and roughs only (MSMA, DSMA,
CAMA)
• Limit turf applications to 1 broadcast treatment and up to 3 subsequent spot
treatments not to exceed 10% of the treatment area (MSMA, DSMA, CAMA)
• Limit turf applications to four total applications of any combination of MSMA,
DSMA, CAMA
• Reduce maximum labeled rate to 3.7 Ibs. ai/A for CAMA
• Prohibit application to impervious surfaces in residential areas
• Prohibit aerial application (except cotton)
• Require chemical resistant gloves for occupational handlers mixing and loading
MSMA, DSMA, CAMA, or cacodylic acid
• Require chemical resistant gloves for occupational handlers applying MSMA,
DSMA, CAMA, or cacodylic acid with handheld equipment
Page 42 of 46
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• Restricting the high application rate of cacodylic acid for lawn renovation to
certified applicators or those operating under the supervision of a certified
applicator
After careful consideration of these options, the Agency has concluded that
implementation of these measures would reduce certain risks; but that cancer risks
through drinking water exposure would remain, for the most part, unchanged. When risk
estimates are recalculated with the proposed mitigation above, excess cancer risk for
cotton use is 3 x 10"4 (3.9 ppb) and excess cancer risk for turf use is 1 x 10"3 (13.1 ppb).
Even with extensive mitigation beyond what was offered by the registrants, EPA believes
the large disparity between the estimated risks and OPP's level of concern for excess
cancer risk of 1 x 10"6 (equivalent to 0.02 ppb of inorganic arsenic) precludes risk
reduction sufficient to reduce levels below OPP's level of concern.
Given that estimated drinking water exposure from the pesticidal uses alone
exceeds EPA's level of concern and that alternative herbicides are readily available, EPA
concludes that the benefits do not outweigh the risks and that all uses for the active
ingredients MSMA, DSMA, CAMA, and cacodylic acid are ineligible for reregi strati on.
D. Food Quality Protection Act Findings and Regulatory Rationale
1. FFDCA/FQPA Findings
a. "Risk Cup" Determination
As part of the FQPA tolerance reassessment process, EPA assessed the risks
associated with the organic arsenical herbicides. EPA has determined that risk from dietary
(food + water) exposure to inorganic arsenic exceeds the "risk cup." EPA did not
aggregate drinking water exposure with food or residential exposures because the risks
posed by drinking water alone are above the LOG and further combination would result in
increased risk estimates that would further exceed the LOG. EPA considered the available
information and has concluded that the tolerances listed under 40 CFR §180.289 (a)(l) and
40 CFR §180.311 (a)(l) do not meet the reasonable certainty of no harm standard under
FFDCA/FQPA.
b. Tolerance Reassessment Summary
Table 25 presents a summary of the organic arsenical herbicides tolerance
reassessment decision. EPA has determined that the 4 established tolerances for MMA
and DMA do not meet the safety standards under Section 408(b)(2)(D) of the FFDCA, as
amended by FQPA. In reaching this conclusion, the Agency has considered all available
information on the toxicity, use practices, and the environmental behavior of the organic
arsenical herbicides. The proposed revocation of the 4 tolerances will be announced in
the Federal Register.
Page 43 of 46
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Table 25. Tolerance Reassessment Summary for the Organic Arsenical Herbicides
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comment
Tolerances Listed Under 40 CFR §180.289 (a)(l) - MSMA/DSMA
Cotton, undelinted seed
Cotton, hulls
Fruit, citrus
0.7
0.9
0.35
Revoke
Revoke
Revoke
This tolerance does not meet the
reasonable certainty of no harm
standard under FFDCA/FQPA.
This tolerance does not meet the
reasonable certainty of no harm
standard under FFDCA/FQPA.
Citrus is not being supported for
reregistration.
Tolerance Listed Under 40 CFR §180.311 (a)(l) - Cacodylic Acid
Cotton, undelinted seed
2.8
Revoke
This tolerance does not meet the
reasonable certainty of no harm
standard under FFDCA/FQPA.
No Codex or Canadian MRLs have been established for MSMA, DSMA, CAMA,
or cacodylic acid.
FDA has established tolerances for total arsenic residues in edible tissues and in
eggs of chickens and turkeys as well as in edible tissues of swine as listed under 21 CFR
§ 556.60. These tolerances are regulated by FDA and are not included in this tolerance
reassessment decision; however, the possible residues from these uses are included in
EPA's dietary risk assessment.
c. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect produced by a
naturally occurring estrogen, or other endocrine effects as the Administrator may
designate." Following recommendations of its Endocrine Disrupter Screening and
Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific
basis for including, as part of the program, the androgen and thyroid hormone systems, in
addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation
that EPA include evaluations of potential effects in wildlife. For pesticides, EPA will use
its authorities under FIFRA and/or the FFDCA to require any necessary data on
endocrine-related effects. As the science develops and resources allow, screening for
additional hormone systems may be added to the Endocrine Disrupter Screening Program
(EDSP).
In the available toxicity studies on MSMA, DSMA, CAMA, and cacodylic acid,
there was no evidence of endocrine disruption effects.
Page 44 of 46
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d. Cumulative Risks
Risks summarized in this document are those that result only from the use of the
organic arsenical herbicides. The Food Quality Protection Act (FQPA) requires that, when
considering whether to establish, modify, or revoke a tolerance, the Agency consider
"available information" concerning the cumulative effects of a particular pesticide's
residues and "other substances that have a common mechanism of toxicity." Unlike other
pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to
the organic arsenical herbicides. EPA has not assumed that the organic arsenical herbicides
share a common mechanism of toxicity with other compounds.
2. Regulatory Rationale for FFDCA/FQPA Findings
While EPA has identified some risk associated with the direct use of the organic
arsenical herbicides, the Agency's primary concern is the potential for applied organic
arsenical products to transform to a more toxic inorganic form of arsenic in soil with
subsequent transport to drinking water.
Dietary exposure from drinking water alone results in risks that exceed OPP's
level of concern for excess cancer risk (1 x 10"6). Estimated drinking water
concentrations for turf result in an excess cancer risk of 3 x 10"3. EDWCs for cotton
result in an excess cancer risk of 3 x 10"4. These estimates may overestimate inorganic
arsenic exposure and risk because the exposure is known to be to a combination of
organic and inorganic arsenic compounds; however, limited monitoring data in areas with
high organic arsenical herbicide use support EPA's risk assessment.
In order for a pesticide tolerance to remain in effect, EPA must generally
determine with reasonable certainty that no harm will result from aggregate exposure to
the pesticide chemical residue. Because the potential pesticide chemical residues in
drinking water alone exceed EPA's LOG, the Agency did not conduct an aggregate
exposure assessment for inorganic arsenic. Further aggregation with other exposure
sources (i.e., food, residential application and post-application activities, or background
sources) would have resulted in increased risk estimates that would have further exceeded
the LOG.
Given that estimated drinking water exposure from the pesticidal uses alone (i.e.,
without food, residential application and post-application activities, or background sources)
exceeds EPA's level of concern, EPA concludes that existing tolerances listed under 40
CFR §180.289 (a)(l) and 40 CFR §180.311 (a)(l) do not meet the reasonable certainty of
no harm standard under FFDCA/FQPA.
E. Policy Considerations
EPA's Office of Water establishes the maximum contaminant level (MCL) for
total arsenic in drinking water. This regulation was established to reduce potential cancer
Page 45 of 46
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risks from background arsenic in drinking water. While the MCL indicates the maximum
allowable concentration of arsenic in drinking water (10 ppb), the MCLg (MCL goal) or
target concentration of arsenic in drinking water is zero (0 ppb). The MCL represents the
highest acceptable level of exposure based on technological and economic limitations,
and the MCLg represents the target level based on adverse human health effects.
Although estimated arsenic exposure in drinking water resulting from pesticidal
uses may, in some cases, be lower than the MCL, allowing additional arsenic exposure in
drinking water as a result of organic arsenical herbicide use would not be consistent with
EPA's goal to minimize arsenic exposure. Continued use of the organic arsenical
herbicides would result in three undesired effects: unnecessary arsenic exposure to
individuals using un-treated water sources; unnecessary arsenic exposure to individuals
using treated water sources that have arsenic levels typically below the MCL; and
additional economic burden to water treatment plants typically above the MCL that
would need to remove additional arsenic from herbicidal use to "clean" water down to the
MCL. Use of organic arsenic herbicides results in an additional, man-made, and
preventable source of arsenic exposure and does not provide meaningful benefit to
society. Thus, OPP's reregi strati on eligibility and tolerance reassessment decisions are in
harmony with broader EPA policy to protect human health and the environment by
minimizing exposure to arsenic.
V. What Registrants Need to Do
EPA has determined that all uses for MSMA, DSMA, CAMA, and cacodylic acid
are ineligible for reregi strati on and that the associated tolerances do not meet the
reasonable certainty of no harm standard. EPA is issuing this Reregi strati on Eligibility
Decision (RED) document for the organic arsenical herbicides, as announced in a Notice
of Availability published in the Federal Register. There is a 60-day public comment
period for this document.
In the near future, EPA intends to initiate appropriate action to revoke tolerances
that do not meet the reasonable certainty of no harm standard identified in this RED.
Also, in the absence of voluntary cancellation requests or substantive comments that
affect EPA's ineligibility decision, EPA intends to initiate cancellation proceedings for
the registrations of pesticide products that are declared ineligible in this RED. These
actions will be announced in the Federal Register and will provide interested persons
with an opportunity to request a hearing for cancellation actions under FIFRA or to
comment and file objections for tolerance proceedings under the FFDCA/FQPA.
Page 46 of 46
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Appendix A. Use Patterns Subject to Reregistration for the
Organic Arsenical Herbicides
-------
Appendix A. Use Patterns Subject to Reregistration for the Organic Arsenical
Herbicides
All uses for MSMA are ineligible for reregi strati on.
All uses for DSMA are ineligible for reregi strati on.
All uses for CAMA are ineligible for reregi strati on.
All uses for cacodylic acid are ineligible for reregi strati on.
-------
Appendix B. Data Supporting Guideline Requirements for the Reregistration of the
Organic Arsenical Herbicides
-------
Appendix B. Data Supporting Guideline Requirements for the Reregistration of the
Organic Arsenical Herbicides
Data Requirement
New
Guideline
Number
Old Guideline
Number
Description
Use Pattern
Citations
PRODUCT CHEMISTRY
830.1550
830.1700
830.1700
830.1750
830.1800
830.6302
830.6302
830.6302
830.6303
830.6304
830.6313
830.7000
830.7200
830.7300
830.7370
830.7370
830.7550
830.7950
61-1
61-3
62-1
62-2
62-3
61-2
63-0
63-2
63-3
63-4
63-13
63-12
63-5
63-7
63-8
63-10
63-11
63-9
Product Identity and
Composition
Discussion of Formation of
Impurities
Preliminary Analysis
Certification of Limits
Analytical Method
Description of Beginning
Materials and Manufacturing
Process
Reports of Multiple
phys/chem Characteristics
Color
Physical State
Odor
Stability to normal and
elevated temperatures, metals,
and metal ions
pH
Melting Point
Density
Solubility
Dissociation Constants in
Water
Partition coefficient, shake
flask method
Vapor Pressure
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
42388301,42053701,
42361001,42051902,
41602701,42387801,
41702001,42474101,
41702002,42153501,
41608101,42913801
42053701,42361001,
42053702,41602701,
41702001,42474101,
41702002,42913801
41608302,42614501,
44150401,42053702,
42825901
41608302,42614501,
42053702,
42387802, 42825901
40957813,42053701,
44150401,42361001,
41602701,42387801,
41702001,42474101,
41702002,42081201,
42913801
42473801,42451102,
42451101
42807602
42807603
42807604
41610001,42378601,
42807609
41982002,42378601,
42807608,
42397101,42403501,
41982001,41789501,
42807605,
42807606
42403501, 41602502,
41610001, 42807607
41976201,41610001
41976202,40957813
42120701,41651901,
ECOLOGICAL EFFECTS
-------
Data Requirement
New
Guideline
Number
850.2100
850.2200
850.1075
850.1010
850.4230
850.4400
875.2100
875.2400
875.2500
850.1045
850.3020
850.4400
Old Guideline
Number
71-1
71-2
72-1
72-2
123-1
123-2
132-1
133-3
133-4
72-3
141-1
123-2
Description
Avian Single Dose Oral
Toxicity
Avian Dietary Toxicity
Acute Toxicity to Freshwater
Fish
Acute Toxicity to Freshwater
Invertebrates
Seed germination/seedling
emergence and vegetative
vigor
Aquatic plant growth
Dissipation of Dislodgeable
Foliar & Soil Residues
Dermal passive dosimetry
expo
Inhal. passive dosimetry expo
Panaeid Acute Toxicity Test
Honey bee acute contact LD50
Aquatic Plant Toxicity
Use Pattern
All
All
All
All
All
All
All
All
All
A,B,D
All
A,B,D
Citations
41608304,42551302,
41892001,41610002,
43316403,
42551301,42551302,
41610003,41610004,
41892002, 41892003,
43316401,43316402
40098001,41748302,
41748301,41608304,
41610002,43316403,
41747301,41748001,
41905601,41905602
41747901,42551301,
41940605
41732301,41732302,
41905604,41905603
41791105,41791101,
41791104,41791102,
41791103
44958901
44459801
44459801
42433301,42433302
42468101,42414102,
42464801,42414101,
41608310,41935401
41791101,41940603,
43184501,43184502,
43184503
TOXICOLOGY
870.3100
870.4200
870.3700
870.4100
870.5380
870.1100
870.2400
870.3200
82-1
83-2
83-3
83-1
84-2
81-1
81-4
82-2
Subchronic Oral Toxicity: 90-
Day Study
Oncogenicity
Teratogenicity ~ 2 Species
Chronic Toxicity
Interaction with Gonadal DNA
Acute Oral Toxicity - Rat
Primary Eye Irritation -
Rabbit
21 -Day Dermal - Rabbit/Rat
All
All
All
All
All
All
All
A,B,D
42767701,42362501
40632601
40625701, 41926401,
159390, 40663301
40546101,41266401,
41490901
41651902,41651903,
41651904,41651905
105171,41892004,
45405601
43840901
41872801,41872701,
42659701
-------
Data Requirement
New
Guideline
Number
870.3465
870.3800
870.4300
870.5100
870.5300
870.7485
870.7600
Old Guideline
Number
82-4
83-4
83-5
84-2
84-2
85-1
85-3
Description
90-day inhal.-rat
2-Generation Reproduction -
Rat
Combined Chronic
Toxicity/Carcinogenicity: Rats
Bacterial Reverse Gene
Mutation
Gene Mutation (CHO)
General Metabolism
Dermal
Penetration/ Absorption
Use Pattern
All
A,B,D
A,B,D
A,B,D
A, B, D
A, B, D
All
Citations
44700301,43178301
43178301,41059501,
41652201
41669001,41862101,
42173201,41914601
42010501,42341301
43497401
ENVIRONMENTAL FATE
835.2120
835.2240
835.2410
835.4100
835.4300
835.4400
835.6100
161-1
161-2
161-3
162-1
162-4
162-3
164-1
Hydrolysis
Photodegradation - Water
Photodegradation - Soil
Aerobic Soil Metabolism
Aerobic Aquatic Metabolism
Anaerobic Aquatic
Metabolism
Terrestrial Field Dissipation
A, B, D
A, B, D
A,B,D
A,B,D
A,B,D
A,B,D
A,B,D
42363001,42059201
41903902,41662601,
41651906,41662602,
41903901
44767601,42616001,
43314801,43036101
44767602,42572601
42843101,4348530,
41302101, 92015007,
43485301,42526001,
42616201,117165
RESIDUE CHEMISTRY
860.1850
860.1300
860.1300
860.1300
860.1340
165-1
171-4 A2
171-4 A3
171-4B
171-4C
Confined Accumulation in
Rotational Crops
Nature of the Residue in
Plants
Nature of the Residue in
Livestock
Nature of Residue - Livestock
(Goat)
Residue Analytical Method -
Plants
A,B,D
All
All
A,B,D
A,B,D
43091101
42886601,42324401,
42391201,43013401,
42216101,42324401
42975001,43059901,
42009701,42009702,
42525002 42525001
44415202,45936601,
45936602, 42009702,
43279301, 43630101,
43630201,43769101,
43802501,44125501,
44825201
44320001,44325801,
44325802,44087401,
44415201,44415203,
42525001, 42525002,
43605901,43817101,
43605901,43683101,
43720701,43803701,
43817101,43959801,
44195901,
OTHER
Non-guideline
Non-guideline
Complete primary report ~
A,B,D
10991
-------
Data Requirement
New
Guideline
Number
Study
Non-guideline
Study
Non-guideline
Study
Old Guideline
Number
Study
Non-guideline
Study
Non-guideline
Study
Description
experimental research
Secondary report attributed to
others
Complete primary report ~
experimental research
Use Pattern
All
All
Citations
46565301
44972201,45496802,
45496803,41054701,
46436501,46436502,
46436503, 46436504,
46671701,44195901,
43605901
-------
Appendix C. Technical Support Documents
-------
Appendix C. Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP
docket, located in Room S-4400, One Potomac Yard (South Building), 1777 S. Crystal
Drive, Arlington, VA. It is open Monday through Friday, excluding legal holidays, from
8:30 AM to 4:00 PM.
The preliminary risk assessments and related documents for the organic arsenical
herbicides are available in the public docket and in e-dockets under docket number EPA-
HQ-OPP-2006-0201. During the public comment period, respondents submitted
comments and additional information on the organic arsenical herbicides. EPA reviewed
and, where appropriate, incorporated this information into the revised risk assessments.
These revised risk assessments form the basis of the regulatory decision described in this
RED. These risk assessment and related documents are available under docket number
EPA-HQ-OPP-2006-0201.
Technical support documents for the organic arsenical herbicides RED include the
following:
Human Health Effects Documents
1. ORGANIC ARSENICS: Final HED Combined Chapter of the Reregistration
Eligibility Decision Document (RED). D329694. June 21, 2006.
2. Organic Arsenicals. Revised Acute and Chronic Dietary Exposure Assessments
for the Reregistration Eligibility Decision (RED). D329695. June 21, 2006.
3. Arsenic: Final Occupational and Residential Exposure Assessment for the
Reregistration Eligibility Decision Document for DMA, CAMA, MSMA, and
DSMA. D329696. June 21, 2006.
4. Revised and updated executive summaries for Cacodylic acid (Dimethylarsinic
acid) and Methanearsonic Acid and the relevant sodium and calcium salts.
DP309103. February 2, 2006.
5. Residue Chemistry Chapter for the Monosodium and Disodium Salts of
Methanearsonic Acid Reregistration Eligibility Decision (RED). D309106.
January 31,2006.
6. Residue Chemistry Chapter for the Cacodylic Acid and Salts Reregistration
Eligibility Decision (RED) Document. D309106. January 31, 2006.
7. Revised Science Issue Paper: Mode of Carcinogenic Action for Cacodylic Acid
(Dimethylarsinic Acid, DMAV) and Recommendations for Dose Response
Extrapolation. January 30, 2006
Environmental Fate and Effects Documents
1. Drinking Water Assessment for Organic Arsenical Herbicides for the
Reregistration Eligibility Decision (RED). D309097. March 29, 2006.
2. Addendum to EFED RED Chapters for Organic Arsenicals Accounting for
Updated Label Rates and Potential for Long Term Buildup in Soil. D309100.
February 3, 2006.
-------
3. Re-registration Eligibility Document for Sodium and Calcium Salts of
Methanearseonic Acid (MSMA/DSMA/CAMA). D277223. September 24, 2001.
4. Environmental Risk Science Chapter for Cacodylic Acid and its Sodium Salt.
D21045 I.March 27, 2000.
Biologic and Economic Analysis Documents
1. Alternatives Assessment of the Organic Arsenical Herbicides Used in Residential
and Golf Course Turfgrass, and Cotton. D309117. April 12, 2006.
-------
Appendix D. Citations Considered to be Part of the Data Base Supporting the
Reregistration Eligibility Decision
-------
Appendix D. Citations Considered to be Part of the Data Base Supporting the
Reregistration Eligibility Decision
MRID Citation Reference
10991 Meisch, M. (1972) AltosidA(TM)14E: Test No. E-36-Del-72. (Unpub- lished study received Dec 22, 1972 under
3G1343; submitted by Zoecon Corp., Palo Alto, Calif.; CDL:095220-U)
105171 Cannelongo, B.; Sabol, E.; Soliz, D.; et al. (1982) Rat Acute Oral Toxicity: Project No. 2558-82. (Unpublished
study received Jun 21, 1982 under 38167-1; prepared by Stillmeadow, Inc., sub- mitted by Setre, Inc., Memphis,
TN; CDL:247705-A)
117165 Sandberg, G.; Allen, I.; Dietz, E. (1973) Arsenic Residues in Soils Treated with Six Annual Applications of
MSMA and ... CA: Project No. 32532-73312. Progress rept, 73 Wes 8-9-10. (Unpublished study received Aug
27, 1976 under 6308-18; submitted by Ansul Chemical Co., Weslaco, TX; CDL:095256-C)
159390 Rubin, Y. (1986) Methanearsonic Acid: Teratology Study in the Rab- bit: PAL/006/MSM. Unpublished study
prepared by Life Science Research Israel Ltd. 170 p.
40098001 Mayer, F.; Ellersieck, M. (1986) Manual of Acute Toxicity: Inter- pretation and Data Base for 410 Chemicals
and 66 Species of Freshwater Animals. US Fish & Wildlife Service, Resource Pub- lication 160. 579 p.
40546101 Waner, T.; Nyska, A. (1988) Methanearsonic Acid: Fifty-two Week Chronic Oral Toxicity Study in Beagle
Dogs: Document Number PAL/MAA/022. Unpublished study prepared by Life Science Re- search Israel, Ltd.
449 p.
40625701 Gal, N.; Rubin Y. (1988) Cacodylic Acid: Teratogenicity Study in the Rat: LSRI Proj. No. PAL/017/CAC.
Unpublished study prepared by Life Science Research Israel Ltd. 261 p.
40632601 Fermenta Plant Protection Co. (1988) Justification for Dose Select- ion in New Methanearsonic Acid (MAA)
Mouse Oncogenicity Study. Unpublished compilation. 184 p.
40663301 Rubin, Y.; Nyska, A. (1988) Cacodylic Acid: Teratogenicity Study in the Rabbit: LSRI Project No.
PAL/019/CAC. Unpublished study prepared by Life Science Research Israel Ltd. 152 p.
40957813 Bellet, E. (1988) Product Chemistry for 3.25 Cacodylate. Unpub- lished study prepared by Luxembourg-Pamol,
Inc. 8 p.
41054701 Knarr, R. (1988) Exposure of Applicators to Propoxur During Trigger Pum Spray Application of a Liquid
Product: 99100. Unpublished study prepared by Mobay Corp. 195 p.
41266401 Waner, T.; Nyska, A. (1988) Methanearsonic Acid Fifty-two Week Chronic Oral Toxicity Study in Beagle
Dogs: Doc. No. PAL/008/MAA. Unpublished study prepared by Life Science Research Israel, Ltd. 48 p.
41302101 Woolson, E. (1989) Terrestrial Field Dissipation of Cacodylic Acid on Turf: Lab Project Number: 127-001: EF-
88-43. Unpublished study prepared by EPL Bio Analytical Services, Inc. 294 p.
41490901 Zomber, G.; Nyska, A.; Waner, T.; et al. (1989) Cacodylic Acid: 52- Week Oral Toxicity Study in Beagle Dogs:
Lab Project Number: PAL/012/CAC. Unpublished study prepared by Life Science Resea- rch Israel Ltd. 751 p.
41602502 Pesselman, R. (1990) Solvent Solubility Determination of Disodium Methanearsonate (DSMA): Final Report:
Lab Project Number: HLA 6001-577. Unpublished study prepared by Hazleton Laboratories America, Inc. 41 p.
41602701 MAA Research Task Force. (1990) MSMA 6.6: Product Identity and Composition. Unpublished study. 9 p.
41608101 Peplowski, M. (1990) Product Identity and Disclosure of Ingredients : Arsonate Liquid/Ansar 6.6 (MSMA).
Unpublished study prepared by Fermenta ASC Corp. 7 p.
41608302 Bellet, E. (1990) Cacodylate 3.25: Analytical Methods. Unpublished study prepared by Luxembourg Industries,
Ltd. 4 p.
41608304 Campbell, S.; Hoxter, K.; Smith, G. (1990) Cacodylate 3.25: An Acute Oral Toxicity Study with the Northern
-------
Bobwhite: Lab Pro-ject Number: 286-104. Unpublished study prepared by Wildlife- International, Ltd. 18 p.
41608310 Hoxter, K.; Smith, G. (1990) 3. 25 Cacodylic Acid: An Acute Contact Toxicity Study with the Honey Bee: Lab
Project Number: 286-101. Unpublished study prepared by Wildlife International Ltd. 13 p.
41610001 MAA Research Task Force Three (1990) MSMA 6.6: Physical and Chemi- cal Characteristics: Final Reports:
Lab Project Number: 1081-89-0355-AS-001; HLA 6001-575. Unpublished study. 234 p.
41610002 Campbell, S.; Hoxter, K.; Smith, G. (1990) MSMA: An Acute Oral Toxicity Study with the Northern Bobwhite:
Lab Project Number: 296-104. Unpublished study prepared by Wildlife International Ltd. 20 p.
41610003 Long, R.; Foster, I; Hoxter, K.; et al. (1990) MSMA: A Dietary LC50 Study with the Northern Bobwhite: Lab
Project Number: 296-102. Unpublished study prepared by Wildlife International Ltd. 6 p.
41610004 Long, R.; Foster, I; Hoxter, K.; et al. (1990) MSMA: A Dietary LC50 Study with the Mallard: Lab Project
Number: 296-103. Un- published study prepared by Wildlife International Ltd. 135 p.
41651901 Lorence, P.; Thomas, E. (1989) Monomethylarsonic Acid (MAA) (SDS- 37161)~Determination of Vapor
Pressure: Lab Project Number: 1081-88-0102-AS-001: 79A. Unpublished study prepared by Ricerca Inc. 58 p.
41651902 Chun, I; Killeen, J. (1989) Salmonella/Mammalian-Microsome Plate IncorporationMutagenicity Assay (Ames
Test) with and without Metabolic Activation with Methanearsonic Acid (MAA): Lab Project Number: 89-0087:
T8471.501014: 88-0223. Unpublished study pre- pared by Microbiological Associates Inc. and Ricerca, Inc. 169
P-
41651903 Chun, J.; Killeen, J. (1989) In Vitro Chromosomal Aberration Assay in Chinese Hamster Ovary (CHO) Cells
withMethaearsonic Acid (MAA): Lab Project Number: 89-0087: T8471.337001: 88-0220. Un- published study
prepared by Microbiological Assoceates Inc. and Ricerca, Inc. 127 p.
41651904 Chun, J.; Killeen, J. (1989) Mutagenesis Assay with Methanearsonic Acid: L5178Y TK+/-Mouse Lymphoma:
Lab Project Number: 89-0087: T8471.701020: 88-0222. Unpublished study prepared by Microbiolo- gical
Associates, Inc. and Ricerca, Inc. 159 p.
41651905 Chun, J.; Killeen, J. (1989) Unscheduled DNA Synthesis Assay in Rat Primary Hepatocytes with
Methanearsonic Acid (MAA): Lab Project Number: 89-0087: T8471.380009: 88-0221. Unpublished study pre-
pared by Microbiological Associates, Inc. and Ricerca, Inc. 130 p.
41651906 Korsch, B.; Kapostasy, W. (1988) Adsorption and Desorption of Mono- sodium Methanearsonate to Soils: Lab
Project Number: 87-0100: 1702-87-0100-EF-001: SDS-36463. Unpublished study prepared by Ricerca, Inc. 59
P-
41652201 Rubin, Y. (1990) Cacodylic Acid: Two Generation Reproduction Study in the Rat: Amendment to Final Report:
Lab Project Number: PAL/015/CAC. Unpublished study prepared by Life Science Research Israel Ltd. 20 p.
41662601 Lawrence, B.; Kesterson, A. (1990) Solution Photolysis of ?carbon- 14| Cacodylic Acid in Natural Sunlight: Lab
Project Number: 455. Unpublished study prepared by Pharmacology & Toxicology Research Laboratory. 71 p.
41662602 Jackson, S.; Kesterson, A. (1990) Soil Surface Photolysis of ?carbon 14| Cacodylic Acid in Natural Sunlight:
Lab Project Num- ber: 456. Unpublished study prepared by Pharmacology & Toxi- cology Research Laboratory.
77 p.
41669001 Crown, S.; Nyska, A.; Waner, T. (1990) Methanearsonic Acid: Combined Chronic Feeding amd Oncogenicity
Study in the Rat: Final Report: Lab Project Number: PAL/004/MAA. Unpublished stu- dy prepared by Life
Science Research Israel Ltd. 1878 p.
41702001 Haefele, L. (1990) Product Identity and Composition: MSMA 660. Un- published study prepared by Drexel
Chemical Co. 24 p.
41702002 Haefele, L. (1990) Analysis and Certification of Ingredient Limits- MSMA 660. Unpublished study prepared by
Drexel Chemical Co. 18 p.
-------
41732301 Chetram, R. (1990) Tier 2 Seed Germination/Seedling Emergence Non- target Phytotoxicity Study Using
Cacodylate 3.25: Lab Project Number: LR90-425. Unpublished study prepared by Pan-Agri- cultural
Laboratories, Inc. 154 p.
41732302 Chetram, R. (1990) Tier 2 Vegetative Vigor Nontarget Phytotoxicity Study Using Cacodylate 3.25: Lab Project
Number: LR90-424. Un- published study prepared by Pan-Agricultural Laboratories, Inc. 60 p.
41747301 Graves, W. (1991) MSMA: A 96 Hour Flow-through Acute Toxicity Test with the Rainbow Trout: Final Report:
Lab Project Number: 296A-104A. Unpublished study prepared by Wildlife International Ltd. 52 p.
41747901 Bellantoni, D.; Peters, G. (1991) Cacodylic Acid: A 48-Hour Flow- through Acute Toxicity Test with the
Cladoceran (Daphnia magna): Final Report: Lab Project Number: 286A-101. Unpublished study prepared by
Wildlife International Ltd. 51 p.
41748001 Graves, W.; Peters, G. (1991) MSMA: A 96-Hour Flow-through Acute Toxicity Test with the Bluegill (Lepomis
macrochirus): Final Report: Lab Project Number: 296A-102. Unpublished study pre- pared Wildlife
International Ltd. 52 p.
41748301 Graves, W.; Peters, G. (1991) Cacodylic Acid: A 96-Hour Flow-Throu- gh Acute Toxicity Test with the
Rainbow Trout (Oncorhynchus mykiss): Lab Project Number: 286A-104. Unpublished study prepared by
Wildlife International Ltd. 50 p.
41748302 Graves, W.; Peters, G. (1991) Cacodylic Acid: A 96-Hour Flow-Throu- gh Acute Toxicity Test with the Bluegill
(Lepomis macrochirus): Lab Project Number: 286A-105. Unpublished study prepared by Wildlife International
Ltd. 50 p.
41789501 Pesselman, R. (1991) Melting Point/Melting Range Determination of Synthetically Prepared Monosodium
Methanearsonate (MSMA): Lab Project Number: HWI6001-685. Unpublished study prepared by Hazleton
Wisconsin, Inc. 23 p.
41791101 Hughes, J. (1991) The Toxicity of Cacodylate 3.25 to Selenastrum capricorutum: Lab Project Number: B648-01-
1. Unpublished study prepared by Malcom Pirnie, Inc. 52 p.
41791102 Hughes, J. (1991) The Toxicity of Cacodylate 3.25 to Anabaene flos- aquae: Lab Project Number: B648-01-2.
Unpublished study pre- pared by Malcolm Pirnie, Inc. 55 p.
41791103 Hughes, J. (1991) The Toxicity of Cacodylate 3. 25 to Navicula pel- liculosa: Lab Project Number: B648-01-3.
Unpublished study pre- pared by Malcom Pirnie, Inc. 55 p.
41791104 Hughes, J. (1991) The Toxicity of Cacodylate 3.25 to Skeletonema costatum: Lab Project Number: B648-01-4.
Unpublished study pre- pared by Malcolm Pirnie, Inc. 53 p.
41791105 Hughes, J. (1991) The Toxicity of Cacodylate 3. 25 to LemaGibba G3: Lab Project Number: B648-01-5.
Unpublished study prepared by Malcolm Pirnie, Inc. 51 p.
41862101 Gur, E.; Nyska, A.; Waner, T. et al. (1989) Cacodylic Acid:Combined Chronic Feeding and Oncogenicity Study
in the Rat: Final Report. Lab Project Number: LSRI PAL/010/CAC. Unpublished study pre- pared by Life
Science Research Israel, Ltd. 221 p.
41872701 Margitich, D.; Ackerman, L. (1991) Methanearsonic Acid: 21 Day Der- mal Toxicity Study in Rabbits: Lab
Project No: PH 430-LI-001-90. Unpublished study prepared by Pharmakon Research International Inc. 549 p.
41872801 Margitich, D.; Ackerman, L. (1991) Cacodylic Acid: 21-Day Dermal Toxicity Study in Rabbits: Lab Project
Number: PH-430-LI-002-90. Unpublished study prepared by Pharmakon Research, Intl. 550 p.
41892001 Campbell, S.; Lynn, S. (1991) DSMA 81 P (Disodium Methanearsonate): An Acute Oral Toxicity Study with
the Northern Bobwhite: Lab Project Number: 296/107. Unpublished study prepared by Wild- life International
Ltd. 19 p.
41892002 Beavers, J.; Grimes, J.; Lynn, S. (1991) DSMA 81 P (Disodium Metha- nearsonate): A Dietary LC50 Study with
the Mallard: Lab Project Number: 296-106. Unpublished study prepared by Wildlife Inter- national Ltd. 60 p.
-------
41892003 Beavers, I; Grimes, I; Lynn, S. (1991) DSMA 81 P (Disodium Metha- nearsonate): A Dietary LC50 Study with
the Northern Bobwhite: Lab Project Number: 296-105. Unpublished study prepared by Wildlife International
Ltd. 57 p.
41892004 Mallory, V. (1991) Acute Exposure Oral Toxicity: DSMA 81P (TECH): Lab Project Number: PH 402-MAA-
001-91. Unpublished study pre- pared by Pharmakon Research International, Inc. 43 p.
41903901 Kesterson, A.; Wick, M. (1991) Soil Surface Photolysis of ?Carbon 14 MSMA in Natural Sunlight: Lab Project
Number: 1367: 537. Unpublished study prepared by PTRL East, Inc. 64 p.
41903902 Kesterson, A.; Lawrence, B. (1991) Solution Photolysis of ?Carbon 14| MSMA in Natural Sunlight: Lab Project
Number: 1369: 536. Unpublished study prepared by PTRL East, Inc. 70 p.
41905601 Murphy, D.; Peters, G. (1991) DSMA 81 P (Disodium Methanearsonate): A 96-Hour Flow-Through Acute
Toxicity Test with the Bluegill (Lepomis Macrochirus): Lab Project Number: 286A-106. Unpub- lished study
prepared by Wildlife International LTD. 80 p.
41905602 Murphy, D.; Peters,G. (1991) DSMA 81 P (Disodium Methanearsonate): A 96 Hour Flow-Through Acute
Toxicity Test With the Rainbowo Trout (Oncorhynchus Mykiss): Lab Project Number: 286A-107. Un-
published study prepared by Wildlife International LTD. 79 p
41905603 Canez, V. (1991) Tier 2 Seed Germination/Seedling Emergence Nontar get Phytotoxicity Study Using DSMA:
Lab Project Number: BL91-446 Unpublished study prepared by Pan-Agricultural Laboratories, Inc. 249 p.
41905604 White, T. (1991) Tier 2 Vegetative Vigor Nontarget Phytotoxicity Study Using DSMA: Lab Project Number:
BL91-447. Unpublished study prepared by Pan-Agriculteral Laboratories, Inc. 195 p.
41914601 Gur, E.; Nyska, A.; Pirak, M.; et al. (1989) Cacodylic Acid: Onco- genicity Study in the Mouse: Lab Project
Number: PAL/014/CAC. Unpublished study prepared by Life Science Research Isreal, Ltd. 1302 p.
41926401 Mizens, M.; Killeen, J. (1990) A Teratology Study in Rats with Methanearsonic Acid: Lab Project Number: 89-
3456: 89-0130. Un- published study prepared by Bio/dynamics Inc., in cooperation with Ricerca, Inc. 490 p.
41935401 Hoxter, K.; Lynn, S. (1991) DSMA 81 P (Disodium Methanearsonate): An Acute Contact Toxicity Study with
the Honey Bee: Lab Project Number: 296-108D. Unpublished study prepared by Wildlife Inter- national Ltd. 14
P-
41940603 Hughes, J.; Alexander, M. (1991) The Toxicity of DSMA 81 9 to Lemna gibba G3 (Duckweed): Lab Project
Number: B648-03-5: 554-8. Un- published study prepared by Malcolm Pirnie, Inc. and PTRL East, Inc. 75 p.
41940605 Hughes, J.; Alexander, M. (1991) The Toxicity of MSMA 51% Aqueous Solution to Daphnia pulex: Lab Project
Number: B648-03-7: 1357. Unpublished study prepared by Malcolm Pirnie, Inc. and PTRL East Inc. 72 p.
41976201 Pesselman, R. (1991) Dissociation Constant Determination of DSMA: Lab Project Number: 6366-102.
Unpublished study prepared by Hazleton Wisconsin, Inc. 35 p.
41976202 Pesselman, R. (1991) Octanol/Water Partition Coefficient Determina- tion of DSMA: Lab Project Number:
6366-101. Unpublished study prepared by Hazleton Wisconsin, Inc. 39 p.
41982001 Pesselman, R. (1991) Melting Point/Melting Range Determination of DSMA: Final Report: Lab Project
Number: HWI6366-104. Unpub- lished study prepared by Hazleton Wisconsin, Inc. 21 p.
41982002 Pesselman, R. (1991) Ph Value Determination of DSMA: Final Report: Lab Project Number: HWI-6366-100.
Unpublished study prepared by Hazleton Wisconsin, Inc. 19 p.
Baumann, G. (1991) Metabolism of 14 Carbon-MSMA inLactating Goats: Dosing, Sample Collection,
Quantitation of Radioactivity and Metabolite Analysis in Milk and Edible Tissues: Lab Project Num- ber:
42009701 90060: RPT0059. Unpublished study prepared by XenoBiotic Labs, Inc. 218 p.
Baumann, G. (1991) Metabolism of 14 Carbon-MSMA in Laying Hens: Metabolite Analysis and Quantitation in
42009702 Eggs and Tissues: Lab Project Number: 90061: RPT0060. Unpublished study prepared by Xenobiotic Labs, Inc.
-------
184 p.
42010501 Wells-Gibson, N.; Marsh, D.; Krautter, G. (1991) Absorption, Distr- ibution and Elimination of ?Carbon 14|-
Methyl MSMA in the Rat: Lab Project Number: 1344: 462E. Unpublished study prepared by by East, Inc. 355 p.
42051902 Owens, E. (1991) Product Identity and Disclosure of Ingredients Disodium Methanearsonate Technical Grade
(DSMA). Unpublished Study prepared by ISK Biotech Corp. 7 p.
42053701 Haefele, L. (1991) Product Identity and Composition: DSMA Products. Unpublished study prepared by Drexel
Chemical Co. 25 p.
42053702 Haefele, L. (1991) Analysis and Certification of Ingredient Limits DSMA Products. Unpublished study prepared
by Drexel Chemical 18 Co. 18 p.
42059201 Lawrence, B.; Kesterson, A. (1991) Hydrolysis of ?carbon 14|Cacody- lie Acid at pH 5, 7 and 9: Lab Project
Number: 1387: 572. Un- published study prepared by PTRL East, Inc. 49 p.
42081201 Lightsey, D.; Feliberti, V. (1991) Description of Beginning Materi- als and Manufacturing Process for Arsonate
Liquid: Amendment #1: Lab Project Number: PC-90-DGL-001-01-01. Unpublished study pre- pared by ISK
Biotech Corp. 12 p.
42120701 Pesselman, R. (1991) Vapor Pressure Determination of DSMA: Lab Project Number: HWI 6366-103.
Unpublished study prepared by Hazleton Wisconsin, Inc. 36 p.
42153501 Owens, E. (1991) Confidential Statement of Formulation: Arson- ate Liquid/Ansar 6. 6 (MSMA)TDaconate
Super. Unpublished study prepared by ISK Biotech Corp. 6 p.
42173201 Gur, E.; Pirak, M.; Waner, T. (1991) Methanearsonic Acid: Oncogenicity Study in the Mouse: Lab Project
Number: PAL/023/MAA. Unpublished study prepared by Life Science Research Israel Ltd. 1680 p.
42216100 MAA (MSMA/DSMA) Research Task Force Three (1992) Submission of Data To Support Registration of
Monosodium Methanearsonate: Pesticide Fate in Plants Study. Transmittal of 1 study.
O'Neal, S.; Johnson, T. (1992) Metabolic Fate and Distribution of ?carbon 14| Monosodium Methanearsonate in
42216101 Cotton: Lab Project Number: 1388: 468. Unpublished study prepared by PTRL East, Inc. 90 p.
42324400 MAA Research Task Force Three (1992) Submission of residue data in support of the reregistration of ?carbon
14|-Monosodium Methanearsonate. Transmittal of 1 study.
O'Neal, S.; Johnson, T. (1992) Metabolic Fate and Distribution of ?carbon 14|-Monosodium Methanearsonate in
Citrus (Lemons): Lab Project Number: 1414: 481. Unpublished study prepared by PTRL East, Inc.; PTRL West,
42324401 Inc. 96 p.
42341301 Gibson, N.; Marsh, J.; Krautter, G. (1992) Absorption, Distribution and Elimination of ?carbon 14| Cacodylic
Acid in the Rat: Lab Project Number: 1415: 461. Unpublished study prepared by PTRL East, Inc. 409 p.
42361001 Haefele, L. (1992) Supplement to Product Chemistry~DSMA Products. Unpublished study prepared by Drexel
Chemical Co. 13 p.
42362501 Crown, S.; Nyska, A. (1992) Cacodylic Acid Toxicity in Dietary Administration to Mice for 13 Weeks: a
Preliminary Study: Revised Final Report: Lab Project Number: PAL/013/CAC. Unpublished study prepared by
Life Science Research Israel Ltd. 200 p.
42363001 Lawrence, B.; Kesterson, A. (1992) Hydrolysis of ?carbon 14|MSMA at pH 5, 7 ans 9: Lab Project Number:
1444: 645. Unpublished study prepared by PTRL East, Inc. 52 p.
42378601 Pesselman, R. (1992) Final Report: Series 63 Product Chemistry Determinations of Monosodium
Methanearsonate, MSMA (pH and Stability): Lab Project Number: 6366-108. Unpublished study prepared by
Hazleton Wisconsin, Inc. 34 p.
42387801 Bellet, E. (1992) Target 6.6: Product Identity and Composition. Unpublished study prepared by Chemical
Consultants International, Inc. 9 p.
-------
42387802 Bellet, E. (1992) Target 6. 6: Analytical Methods. Unpublished study prepared by Chemical Consultants
International, Inc. lip.
42388301 Bellet, E. (1992) DSMA 81 P: Product Identity and Composition. Unpublished study prepared by Chemical
Consultants International. 9 p.
42391200 MAA (MSMA/DSMA) Research Task Force Three (1992) Submission of Amended Data To Support
Registration of Monosodium Methanearsonate: Plant Metabolism Study. Transmittal of 1 study.
O'Neal, S.; Johnson, T. (1992) Metabolic Fate and Distribution of ?carbon 14|-Monosodium Methanearsonate in
Citrus (Lemons): Lab Project Number: 1414: 481. Unpublished study prepared by PTRL East, Inc., and PTRL
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