SEPA
United States Prevention, Pesticides EPA 738-R-04-014
Environmental Protection and Toxic Substances September 30, 2004
Agency (7508C)
Reregistration Eligibility
Decision (RED) for
Cycloate
(5-ethylcyclohexyl(ethyl)thiocarbamate)
-------
< ^^^^ 2
* WiPf S
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460-0001
-
'ji-j.;-.-j? OFFICE OF
erf* PREVENTION, PESTICIDES
PROW- AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
This is to inform you that the U.S. Environmental Protection Agency (hereafter referred to as
EPA or the Agency) has completed its review of the available data and public comments received
related to the risk assessments for the herbicide cycloate (S'-ethyl cyclohexyl(ethyl)thiocarbamate).
The enclosed Reregistration Eligibility Decision (RED) document for cycloate was approved on
September 30, 2004. Public comments and additional data received were considered in this decision.
Based on its review, EPA has identified risk mitigation measures that the Agency believes are
necessary to address the human health risks associated with the current use of cycloate. EPA is now
publishing its reregistration eligibility and risk management decisions for the current uses of cycloate,
and its associated human health risks. A Notice of Availability will be published in the Federal
Register announcing a 60-day public comment period on the cycloate risk management decision. If
substantive data or comments are received and indicate that any of the Agency's assumptions need to
be refined and that alternate risk mitigation is warranted, EPA will make appropriate modifications at
that time.
The RED and technical supporting documents for cycloate are available to the public through
EPA's electronic public docket and comment system, EPA Dockets, under docket identification (ID)
number OPP-2004-0234. The public may access EPA Dockets at http://www.epa. sov/edockets. In
addition, the cycloate RED may be downloaded or viewed through the Agency's website at
http://www.epa. sov/pesticides/reregistration/status.htm. Earlier information on cycloate, including public
comments, can be found in EPA Dockets under docket ID number OPP-2004-0077.
The Cycloate RED was developed through EPA's public participation process, published in the
Federal Register on May 14, 2004, which provides opportunities for public involvement in the
Agency's pesticide tolerance reassessment and reregistration programs. Developed in partnership
with USDA and with input from EPA's advisory committees and others, the public participation
process encourages robust public involvement starting early and continuing throughout the pesticide
risk assessment and risk mitigation decision-making process. The public participation process
encompasses full, modified and streamlined versions that enable the Agency to tailor the level of
review to the level of refinement of the risk assessments, as well as to the amount of use, risk, public
concern and complexity associated with each pesticide. Using the public participation process, the
Agency is attaining its strong commitment to both involve the public and meet statutory deadlines.
-------
Please note that the risks summarized in the attached RED are those that result only from the
use of cycloate. The Food Quality Protection Act requires that 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." The Agency has determined that some
thiocarbamates (EPTC, molinate, pebulate and cycloate) share a common mechanism of toxicity, the
inhibition of acetylcholinesterase. In September 2001, the Scientific Advisory Panel (SAP)
concluded that there is insufficient evidence for grouping the thiocarbamate pesticides based on a
common mechanism of toxicity for effects other than acetylcholinesterase inhibition. The Agency
conducted a preliminary "screening level" cumulative food risk assessment for the thiocarbamates.
The results of this assessment, using very conservative Tier 1 exposure assumptions, is that MOEs
exceed 310 for all population subgroups. Any MOE greater than 100 is deemed acceptable by EPA.
Therefore, at this time, EPA concludes that the potential cumulative risks from the thiocarbamates in
general and cycloate in particular passes the "reasonable certainty of no harm" standard of the FQPA.
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 OPP concerning common mechanism determinations and procedures for cumulating effects from
substances found to have a common mechanism at http://www.epa.sov/pesticides/cumulative.
The Agency is in the process of developing criteria for characterizing and testing endocrine
disrupting chemicals and plans to implement an Endocrine Disrupter Screening Program in the near
future. Cycloate will be reevaluated at that time and additional testing may be required.
This RED also contains both generic and product-specific data that the Agency intends to
require in Data Call-Ins (DCIs). Note that DCIs, with all pertinent instructions, will be sent to
registrants at a later date. Additionally, for product-specific DCIs, the first set of required responses
will be due 90 days from the receipt of the DCI letter. The second set of required responses will be
due eight months from the receipt of the DCI letter.
As part of the RED, the Agency has determined that cycloate will be eligible for reregistration
provided that all the conditions identified in this document are satisfied, including implementation of
the risk mitigation measures outlined in Section IV of the document. Sections IV and V of this RED
document describe labeling amendments for end-use products and data requirements necessary to
implement these mitigation measures. Instructions for registrants on submitting the revised labeling
can be found in the set of instructions for product-specific data that accompanies this document.
Should a registrant fail to implement any of the risk mitigation measures outlined in this
document, the Agency will continue to have concerns about the risks posed by cycloate. Where the
Agency has identified any unreasonable adverse effect to human health and the environment, the
Agency may at any time initiate appropriate regulatory action to address this concern. At that time,
any affected person(s) may challenge the Agency's action.
-------
If you have any questions on this document or the label changes necessary for reregistration,
please contact the Chemical Review Manager for cycloate, Carmen Rodia, at (703) 306-0327. For
questions about product reregistration and/or the Product DCI that accompanies this document, please
contact Moana Appleyard at (703) 308-8175.
/S/
Debra Edwards, Ph.D.
Director, Special Review and
Reregistration Division
Attachment
-------
-------
Reregistration Eligibility Decision
for
Cycloate
(S'-ethylcyclohexyl(ethyl)thiocarbamate)
ListB
Case 2125
Approved By:
/S/
Debra Edwards, Ph.D.
Director, Special Review and
Reregistration Division
September 30, 2004
Date
-------
-------
Table of Contents
Cycloate Reregistration Eligibility Decision Team
Executive Summary v
I. Introduction 1
n. Chemical Overview 2
A. Regulatory History 2
B. Chemical Identification 3
C. Use Profile 4
D. Estimated Usage of Pesticide 5
m. Summary of Cycloate Risk Assessments 6
A. Human Health Risk Assessment 6
1. Dietary Risk from Food 6
a. Toxicity of Cycloate 7
b. FQPA Safety Factor 9
c. Population Adjusted Dose 9
d. Exposure Assumptions 10
e. Dietary (Food) Risk Assessment 10
2. Dietary Risk from Drinking Water 12
3. Residential and Other Nonoccupational Exposure 15
4. Aggregate Risk 15
5. Occupational Risk 16
a. Occupational Toxicity 16
b. Occupational Exposure 17
c. Occupational Handler Risk Summary 19
B. Environmental Risk Assessment 23
1. Fate and Transport 24
2. Ecological Risks 25
IV. Risk Management, Reregistration and Tolerance Reassessment Decision 32
A. Determination of Reregistration Eligibility 32
B. Regulatory Position 33
1. Food Quality Protection Act Findings 33
a. Determination of Safety for U.S. Population 33
b. Aggregate Dietary Risks 33
c. Determination of Safety for Infants and Children 34
2. Endocrine Disrupter Effects 34
3. Cumulative Risks 35
C. Tolerance Reassessment Summary 35
-------
D. Regulatory Rationale 38
1. Human Health Risk Mitigation 39
2. Environmental Risk Mitigation 42
E. Other Labeling Requirements 44
1. Endangered Species 44
2. Spray Drift Management 45
3. For Commercial Use Only 45
V. Actions Required of Registrants 46
A. Manufacturing-Use Products 46
1. Additional Generic Data Requirements 46
2. Labeling for Manufacturing-Use Products 49
B. End-Use Products 49
1. Additional Product-Specific Data Requirements 49
2. Labeling for End-Use Products 49
C. Labeling Changes Summary Table 50
D. Existing Stocks 56
VI. Appendices 57
Appendix A Table of Use Patterns Eligible for Reregistration 59
Appendix B Data Supporting Guideline Requirements for the Reregistration of
Cycloate 61
Appendix C Technical Support Documents 67
AppendixD Citations Considered to Be Part of the Data Base Supporting the
Reregistration Eligibility Decision (Bibliography) 69
Appendix E EPA's Batching of Cycloate Products for Meeting Acute Toxicity Data
Requirements for Reregistration 83
Appendix F List of Available Related Documents and Electronically Available
Forms 85
Appendix G Generic Data Call-In 89
Appendix H Product-Specific Data Call-In 91
Appendix I List of All Registrants Sent This Data Call-in 93
-------
Cycloate Reregistration Eligibility Decision Team
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
Bill Phillips
David Donaldson
Nicole Zinn
Virginia Werling
Biological Analysis Branch
Economic Analysis Branch
Biological Analysis Branch
Herbicide & Insecticide Branch
Environmental Fate and Effects Risk Assessment
Bill Eckel
Mike Davy
Health Effects Risk Assessment
Barry O'Keefe
David Soderberg
John Liccione
Registration Support
Ching-Tsen Bien
Risk Management
Carmen Rodia
Tom Myers
Environmental Risk Branch II
Environmental Risk Branch U
Reregistration Branch HI
Reregistration Branch III
Reregistration Branch III
Herbicide Branch
Reregistration Branch U
Reregistration Branch II
-------
11
-------
Glossary of Terms and Abbreviations
AGDCI Agricultural Data Call-In
a.i. Active Ingredient
aPAD Acute Population Adjusted Dose
AR Anticipated Residue
BCF Bioconcentration Factor
CAS Chemical Abstract Service
CFR Code of Federal Regulations
cPAD Chronic Population Adjusted Dose
CSF Confidential Statement of Formula
CSFII USDA Continuing Surveys for Food Intake by Individuals
DCI Data Call-In
DEEM Dietary Exposure Evaluation Model
DFR Dislodgeable Foliar Residue
D WLOC Drinking Water Level of Comparison
EC Emulsifiable Concentrate Formulation
EC25 or EC50 Effective Concentration (EC25 for terrestrial plants and EC50 for aquatic plants and invertebrates). The
concentration of a chemical in water at which an effect is observed that is 25% or 50% of the
maximum effect.
EEC Estimated Environmental Concentration The estimated pesticide concentration in an environment,
such as a terrestrial ecosystem
EP End-Use Product
EPA United States Environmental Protection Agency
FAO Food and Agriculture Organization
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide and Rodenticide Act
FFDCA Federal Food, Drug and Cosmetic Act
FQPA Food Quality Protection Act
FOB Functional Observation Battery
GENEEC Tier I Surface Water Computer Model
GLC Gas Liquid Chromatography
GLN Guideline Number
HOT Highest Dose Tested
IR Index Reservoir
LC50 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.
LD50 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 an animal, e.g., mg/kg.
LEL Lowest Effect Level
LOAEC Lowest Observed Adverse Effects Concentration. The lowest concentration in an experiment at which
an "adverse" health effect is seen (kg body weight/day).
LOAEL Lowest Observed Adverse Effects Level
LOG Level of Concern
LOD Limit of Detection
MATC Maximum Acceptable Toxicant Concentration
ug/g Micrograms Per Gram
ug/L Micrograms Per Liter
mg/kg/day Milligram Per Kilogram Per Day
mg/L Milligrams Per Liter
MOE Margin of Exposure
ill
-------
MRID Master Record Identification (number). The EPA's system of recording and tracking studies
submitted.
MUP Manufacturing-Use Product
NA Not Applicable
NAWQA USGS National Water Quality Assessment
NOAEC No Observed Adverse Effect Concentration
NR Not Required
NOAEC No Observed Adverse Effects Concentration. The highest concentration of a substance a group of
experimental animals is exposed to that demonstrates the absence of adverse effects observed or
measured at higher concentration levels (kg body weight/day).
NOAEL No Observed Adverse Effects Level
OPP EPA Office of Pesticide Programs
OPPTS EPA Office of Prevention, Pesticides and Toxic Substances
Pa Pascal. The pressure exerted by a force of one newton acting on an area of one square meter.
PAD Population Adjusted Dose
PCA Percent Crop Area
PDF USDA Pesticide Data Program
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
ppm Parts Per Million
PPE Personal Protective Equipment
PRN Pesticide Registration Notice
PRZM/EXAMS Pesticide Root Zone Model and Exposure Analysis Modeling System, which is a Tier II surface water
computer model.
Q! * The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RAC Raw Agriculture Commodity
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RQ Risk Quotient
SCI-GROW Screening Concentration in Ground Water modeling system, which is a Tier I ground water computer
model.
SAP Science Advisory Panel
SF Safety Factor
SLC Single Layer Clothing
SLN Special Local Need (Registrations under section 24(c) of FIFRA)
TC Toxic Concentration. The concentration at which a substance produces a toxic effect.
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TLC Thin LayerChromatography
torr A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
TRR Total Radioactive Residue
UF Uncertainty Factor
USDA United States Department of Agriculture
USEPA United States Environmental Protection Agency
USGS United States Geological Survey
WPS Worker Protection Standard
IV
-------
Executive Summary
This document presents the Agency's decision regarding the reregistration eligibility of the
registered uses of cycloate. This document also presents the Agency's tolerance reassessment
decision for cycloate, which includes the consideration of risk to infants and children for any potential
dietary, drinking water, dermal, inhalation or oral exposures. The Agency made its tolerance
reassessment decision based on the data required for reregistration, the current guidelines for
conducting acceptable studies to generate such data, and published scientific literature. The Agency
has found that the current uses of cycloate on garden beets, spinach and sugarbeets are eligible for
reregistration, provided the changes specified in this document are made to the labels.
Use Summary
Cycloate is a broad-spectrum, pre-emergent herbicide registered for the control of annual
grasses, certain perennial grasses and many broadleaf weeds on garden beets, spinach and sugarbeets.
A new use on Swiss chard has been proposed by the IR-4 program. Cycloate is not for
homeowner/garden use.
Sugarbeets account for more than 90% of cycloate usage. EPA estimates that approximately
679,000 pounds of active ingredient (a.i.) are used annually on a total of approximately 288,000 acres.
Spinach accounts for almost 7% of cycloate usage with 45,000 pounds of a.i. applied per year on
average. Garden beets receive about 17,000 pounds of a.i. annually on just under 8,000 acres treated,
nearly 100% crop treated on garden beet acres.
Carcinogenicity Classification
Cycloate is classified as "not likely to be a carcinogen to humans," therefore, no assessments
were performed for cancer.
Dietary Risks
No population subgroup, including infants and children, exceeded the Agency's level of
concern for either acute or chronic dietary exposure to cycloate based upon aggregated exposure to
food plus water; therefore, no mitigation was warranted for dietary exposure to cycloate.
Worker Risks
The Agency has determined that there is potential for short- and intermediate-term exposures in
occupational settings from handling cycloate products during the application process (i.e.,
mixer/loader, applicator and mixer/loader/applicator). Short- and intermediate-term dermal risk
estimates for most scenarios exceed the Agency's level of concern at baseline personal protective
equipment (PPE). However, most of these exposures can be mitigated by some level of PPE and/or
engineering controls. Risk estimates from inhalation exposures remain a concern for most scenarios,
even with maximum PPE and/or engineering controls. Mitigation measures include the voluntary
-------
cancellation of the chemigation application of cycloate, requiring engineering controls (including
closed cabs and closed mixing/loading systems), prohibiting on-farm impregnation of cycloate onto
dry bulk fertilizer, and requiring use data to better characterize exposure from dry bulk fertilizer
applications.
Post-application exposures are expected to be negligible because cycloate is incorporated into
the soil either immediately or within a few hours after application, or it is injected into the soil. As a
result, post-application scenarios were not assessed. However, due to the volatility of cycloate, the
REI will be increased from the current 12 hours to 48 hours.
Residential and Other Nonoccupational Risks
Cycloate is not registered for any residential (home/garden) or other nonoccupational use, nor is
it to be used in or around public buildings, schools or recreational areas where children or others
might be exposed. Thus, there is no residential exposure to aggregate with the dietary exposure.
Ecological Risks
Cycloate use on garden beets, spinach and sugarbeets may cause adverse ecological effects at
the current maximum application rate of 4 Ibs. a.i./acre. Chronic risks are potentially a concern for
small mammals, birds and estuarine/marine fish and invertebrates. Based on the Agency's screening
level assessment, levels of concern have been exceeded for endangered species of small mammals
(chronic risk) and potentially for birds (chronic risk). These findings are based solely on EPA's
screening level assessment and do not constitute "may affect" findings under the ESA.
Currently, the Agency does not have data to determine the risk from cycloate use on spinach
near estuarine areas to nontarget terrestrial plants. In addition, no acceptable chronic avian
reproduction data were available, so chronic risks for avian species could not be assessed. Data are
required to address these gaps in the ecological assessment.
Cumulative Risk
Section 408(b)(2)(D)(v) of the FFDCA 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." OPP has determined that some thiocarbamates (EPTC, molinate, pebulate and cycloate)
share a common mechanism of toxicity, the inhibition of acetylcholinesterase. In September 2001,
the Scientific Advisory Panel (SAP) concluded that there is insufficient evidence for grouping the
thiocarbamate pesticides based on a common mechanism of toxicity for effects other than
acetylcholinesterase inhibition. Although structural and metabolic similarities exist among the
thiocarbamates and there is evidence that the thiocarbamates may produce a common effect
(neuropathology); however, this evidence is not definitive. The Agency has conducted a preliminary
"screening level" cumulative food risk assessment for the thiocarbamates.
VI
-------
The results of the screening level cumulative food risk assessment, using very conservative Tier
1 exposure assumptions (using tolerance level residues, assuming 100% of all crops treated and
including exposures from molinate, which is being phased out), is that MOEs exceed 310 for all
population subgroups. These results are reported in a memorandum dated December 19, 2001 from
Marcia Mulkey entitled, "Thiocarbamates: A Determination of the Existence of a Common
Mechanism of Toxicity and a Screening Level Cumulative Food Risk Assessment." This document
can be found under thiocarbamates at the EPA website entitled, "Public Comment Period Opened:
Common Mechanism Determination for Thiocarbamate and Dithiocarbamate Pesticides" at
http://www.epa.sov/oppsrrdl/cumulative/thiocar.htm. Since any MOE greater than 100 is deemed
acceptable, the Agency has concluded that the potential cumulative risks from the thiocarbamates in
general and cycloate in particular passes the "reasonable certainly of no harm" standard of the Food
Quality Protection Act.
Summary of Mitigation
Pesticide mixer, loader and applicator risks will be mitigated by a combination of increased
personal protective equipment, use of engineering controls and revised label language. Specifically,
the following mitigation measures will reduce risks to agricultural workers:
Voluntary cancellation of chemigation application of cycloate;
Extend the cycloate REI to 48-hours;
Require engineering controls including closed cabs and closed mixing/loading systems;
• Prohibit on-farm impregnation of cycloate onto dry bulk fertilizer; and
• Require use data to better characterize exposure from dry bulk fertilizer applications.
vn
-------
Vlll
-------
I. Introduction
The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) was amended in 1988 to
accelerate the reregistration 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 reregistration of an
active ingredient, as well as a review of all submitted data by the U.S. Environmental Protection
Agency (referred to as EPA or the Agency). Reregistration involves a thorough review of the
scientific database underlying a pesticide's registration. The purpose of the Agency's review is to
reassess the potential hazards arising from the currently registered uses of the pesticide; to determine
the need for additional data on health and environmental effects; and to determine whether or not the
pesticide meets the "no unreasonable adverse effects" criteria of FIFRA. Congress also passed the
Pesticide Registration Improvement Act of 2003 to set time frames for the issuance of Reregistration
Eligibility Decision (RED) documents.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into law.
FQPA amends FIFRA to require reassessment of all tolerances that were in existence at the time of
enactment by 2006. The Agency has decided that, for those chemicals that have tolerances and are
undergoing reregistration, the tolerance reassessment will be completed through the reregistration
process.
FQPA also amends the Federal Food, Drug and Cosmetic Act (FFDCA) to require a safety
finding in tolerance reassessment based on factors including an assessment of a particular pesticide's
residues and "other substances that have a common mechanism of toxicity." The reason for
consideration of other substances is due to the possibility that low-level exposures to multiple
chemical substances that cause a common toxic effect by a common mechanism could lead to the
same adverse health effect as would a high level of exposure to any one of the other substances
individually. OPP has determined that some thiocarbamates (EPTC, molinate, pebulate and cycloate)
share a common mechanism of toxicity, the inhibition of acetylcholinesterase. Further, in September
2001, the SAP concluded that there is insufficient evidence for grouping the thiocarbamate pesticides
based on a common mechanism of toxicity for effects other than acetylcholinesterase inhibition.
This document presents the Agency's decision regarding the reregistration eligibility of the
registered uses of cycloate, including the consideration of risk to infants and children for any potential
food, drinking water, dermal, inhalation or oral exposures. In an effort to simplify the RED, the
information presented herein is summarized. More detailed information can be found in the technical
supporting documents (risk assessments) for cycloate referenced in this RED. The risk assessments
and related addenda are not included in this document, but are available on the Agency's website at
http://www.epa.sov/pesticides/reresistration/status.htm, and in the OPP Public Docket.
This document consists of six sections. Section I is the introduction. Section II provides a
profile of the use and usage of cycloate and its regulatory history. Section III gives an overview of
the human health and environmental effects risk assessments, based on the data and information
available to the Agency. Section IV presents the reregistration eligibility and risk management
decisions for cycloate. Section V summarizes the label changes necessary to implement the risk
1
-------
mitigation measures outlined in Section IV. Finally, in Section VI, the Appendices list all related
documents and how to access them, and the Data Call-In (DCI) information.
n. Chemical Overview
A. Regulatory History
Cycloate (^-ethyl cyclohexyl(ethyl)thiocarbamate) was first registered in the United States on
July 13, 1967, for use as a selective herbicide on sugarbeets and spinach by the Stauffer Chemical
Company. The use of cycloate on garden beets was first approved on January 9, 1970. Stauffer
Chemical Company transferred the cycloate registrations to ICI Americas, Inc. on December 23,
1987. On January 24, 1994, the registrant name was changed to Zeneca Agrochemicals. Zeneca
Agrochemicals merged with Novartis Agribusiness in November 2000 to form Syngenta Crop
Protection, Inc. Syngenta Crop Protection, Inc. sold all proprietary rights for cycloate to TRIAG,
Inc. on December 1, 2000. Helm Agro US, Inc. is now the agent for TRI AG, Inc.
Cycloate was the subject of a Registration Standard Guidance Document that was issued on
December 7, 1988 and the Residue Chemistry Science Chapter of the Guidance Document (Phase 4
reviews of available residue chemistry data) was issued on December 20, 1990. These documents
summarized the regulatory conclusions based on available residue chemistry data and specified the
updated generic and product-specific chemistry data required by the Agency to support the continued
use of cycloate. In addition to the data requirements in the 1988 Guidance Document, Data Call-in
(DCI) notices were issued on April 5, 1991 and October 18, 1995. The data received in response to
the DCIs were used to reach the reregistration eligibility conclusions for cycloate that are presented in
this RED.
In an effort to promote transparency of the reregistration process and include the public in
developing regulatory decisions, the Agency has developed a public participation process that is used
for pesticide tolerance reassessment and reregistration. This public participation process was
developed in partnership with USD A, based on EPA's and USDA's experiences with the pilot public
participation process used for the organophosphate pesticides, comments received from Tolerance
Reassessment Advisory Committee and the public during the public comment period on the proposed
process and EPA's experience with the interim process used in developing decisions for a number of
non-organophosphate pesticides during the past few years. The public participation process
encompasses full and modified versions that enable EPA to tailor the level of review to the level of
refinement of the risk assessments, as well as to the amount of use, risk, public concern and
complexity associated with each pesticide.
The Agency followed a 4-phase, modified public participation process for cycloate. Consistent
with this process, EPA initiated Phase 1 of the process on March 1, 2004, by transmitting the
preliminary human health and ecological risk assessments to the technical registrant for a 30-day
error only correction review. In Phase 2, EPA considered the errors that were identified by the
registrant and made changes in the risk assessments as appropriate. To initiate Phase 3 of the process
-------
on May 12, 2004, the Agency published a. Federal Register notice announcing the availability of the
revised risk assessments and supporting documents for a 60-day public review and comment period.
EPA received only 20 comments during this period, most expressing a need for the continued use of
cycloate on garden beets, spinach and sugarbeets. None of the submitted comments were specific to
the revised risk assessments or potential risk mitigation measures.
B. Chemical Identification
Pure cycloate is a colorless liquid and technical-grade cycloate is an amber liquid at room
temperature with a density of 1.0243 g/ml at 20° C and an octanol/water partition coefficient (Kow) of
13,000 at 20° C. Cycloate has a moderately high vapor pressure of 6.2 x 10"3 mm Hg at 25° C, so that
losses due to volatilization or sublimation are expected to be significant. Henry's Law constant is
therefore a relatively high 1.85 x 10"5 atm-m3/mol. Cycloate has a moderate solubility in water of 93
mg/L at 25° C and is completely soluble in acetone, chlorobenzene, ethanol, kerosene, methyl
chloride, xylene and n-octanol.
• Common Name:
• CAS NT-1 Systematic
Chemical Name:
• Other Name:
• Chemical Family:
• Case Number:
• Empirical Formula:
• Molecular Weight:
Cycloate [BSI, ISO & WSSA]
^-ethylcyclohexylethyl carbamothioate
S-ethyl cyclohexyl(ethyl)thiocarbamate [IUPAC]
Thiocarbamate
2125
• CAS Registry Number: 1134-23-2
• OPP Chemical Code: 041301
CnH21NOS
215.4g/mole
-------
• Trade Name(s): RO-NEET® 6-E and Cycloate 6-E
• Basic Manufacturer(s): TRIAG, Inc. and Helm Agro US, Inc.
C. Use Profile
The following is information on the currently registered uses of cycloate products with an
overview of use sites and application methods. A detailed table of the uses of cycloate eligible for
reregistration is contained in Appendix A.
Type of Pesticide:
Summary of Use:
Food:
Non-Food:
Residential:
Target Pests:
Formulation Types:
Herbicide
Cycloate is a broad-spectrum, pre-emergent herbicide registered for
the control of annual grasses, certain perennial grasses and many
broadleaf weeds. Cycloate acts by interfering with the germination of
seeds and development of seedlings.
Cycloate is used on garden beets, spinach (fresh and processed) and
sugarbeets. A new use on Swiss chard has been proposed by IR-4.
There are no registered non-food uses of cycloate products.
There are no registered residential uses of cycloate products.
Annual grasses; barley (Hordeum spp.); barnyardgrass, watergrass
(Echinochloa spp.); black nightshade (Solanum nigrum); burning nettle,
small stinging nettle (Uteca urens); common lambsquarters
(Chenopodium album)] common purslane (Portulaca oleracea)] foxtail
(Setaria spp.); hairy nightshade (Solanum villosum); henbit (Lamium
spp)', nettleleaf goosefoot (Chenopodium murale\ nutsedge (Cyperus
spp.)', Pennsylvania smartweed (Polygonumpensylvanicum)] redroot
pigweed (Amaranthus retrqflexus); shepherdspurse (Capsella
bursapastoris); velvet!eaf (Abutilon theophrasti); wild buckwheat
(Polygonum convolvulus)', and wild oat (Avenafatua).
Formulated as an emulsifiable concentrate liquid, 73.9% active
ingredient (a.i.).
-------
Methods and Rates of Application:
Equipment:
Application Rates:
Timing:
Use Classification:
Cycloate is typically applied using groundboom equipment and then
incorporated into the soil mechanically or by sprinkler irrigation
(chemigation).
Typical application rates are similar on all three crops, ranging from 2
to 3 Ibs. a.i./acre. Maximum labeled application rate is 4 Ibs. a.i./acre.
Applied as a pre-plant or at-planting treatment.
General Use.
D. Estimated Usage of Pesticide
Table 1 summarizes the best estimates available for the uses of cycloate. The estimate for total
domestic use (annual average) is approximately 679,000 pounds of a.i. on approximately 288,000
acres treated. More than 90% of cycloate's total usage is on sugarbeets, with an estimated annual
average application of 617,000 pounds of a.i. used on 261,000 acres. Spinach accounts for almost 7%
of cycloate usage with 45,000 pounds of a.i. applied per year on average. Garden beets receive about
17,000 pounds of a.i. annually on just under 8,000 acres treated, nearly 100% crop treated on garden
beet acres.
Table 1. Cycloate Usage Summary.
Site
Garden Beets
Spinach, Fresh
Spinach, Processed
Sugarbeets
Lbs. Active Ingredient Applied
(Weighted Average)1
17,000
32,000
14,000
617,000
Percent Crop Treated
(Estimated Maximum)2
100%
68%
55%
24%
Percent Crop Treated
(Weighted Average)
98%
56%
42%
17%
1 Weighted Average = the most recent years and more reliable data are weighted more heavily.
2 Estimated Maximum = the maximum percentage amount applied as estimated from available data.
Usage data primarily covers 1988 through 1999.
Calculations of the above numbers may not appear to agree because they are displayed as rounded:
to the nearest 1,000 for acres treated or Ibs. a.i.
to the nearest whole percentage point for % of crop treated.
Sources: EPA proprietary data, USDA/NASS, CAL EPA and National Center for Food and Agricultural Policy.
-------
HI. Summary of Cycloate Risk Assessments
The following is a summary of EPA's human health and ecological effects risk findings and
conclusions for the herbicide cycloate, as presented fully in the documents: "Cycloate In/On Spinach,
Garden Beets, Sugarbeets and Swiss Chard. Health Effects Division (HED) Risk Assessment," dated
January 28, 2004; "Cycloate: Reregistration Eligibility Document Science Chapter, PC Number
041301, Environmental Fate and Effects Division (EFED)," dated August 23, 2002; and any
subsequent addenda which are cited within the RED.
The purpose of this section is to summarize the key features and findings of the risk assessments
in order to help the reader better understand the conclusions reached in the assessments. Risks
summarized in this RED document are those that result only from the use of cycloate. While the risk
assessments and related addenda are not included in this RED, they are available in their entirety from
the OPP Public Docket and may also be accessed on the Agency's website at
http://www.epa. sov/pesticides/reregistration/status. htm.
A. Human Health Risk Assessment
1. Dietary Risk from Food
A brief overview of the toxicity studies used for endpoints in the dietary risk assessment is
outlined below in Table 2. Further details on the toxicity of cycloate can be found in the "Cycloate
In/On Spinach, Garden Beets, Sugarbeets and Swiss Chard. Health Effects Division (HED) Risk
Assessment," dated January 28, 2004 and the "Cycloate Toxicology Disciplinary Chapter for the
Reregistration Eligibility Decision Document," dated September 10, 2003.
Table 2. Summary of Cycloate Dietary Toxicity Endpoints.
Exposure
Scenario
Acute Dietary (U.S. General
Population including infants
and children)
Chronic (Noncancer) Dietary
Dose
(mg/kg/day)
LOAEL = 200
NOAEL=N/A
UF = 300
UFDB= 10
Total UF = 3,000
Endpoint
Neuronal cell necrosis in the
pryriform cortex and/or
dentate gyrus.1
Study
(MRIDNo.)
Acute neurotoxicity study in rats
(42921701,43968001)
Acute RID = 0.066 mg/kg/day Acute PAD = 0.066 mg/kg/day
LOAEL = 3.1
NOAEL=0.5
UF=100
Spinal nerve axonal atrophy
and femoral nerve alterations
in female rats.2
Chronic toxicity /carcinogenicity
study in rats (00137735)
Chronic RfD = 0.005 mg/kg/day Chronic PAD = 0.005 mg/kg/day
1 Cycloate may cause damage and death to nerve cells in various parts of the brain and spinal cord.
2 Cycloate can cause damage to various nerves.
-------
a. Toxicity of Cycloate
The Agency has reviewed all toxicity studies submitted for cycloate and has determined that the
toxicological data base for cycloate is considered adequate for hazard characterization.
Acute Toxicity: A brief overview of the acute toxicity of cycloate is in Table 3. Cycloate has a
low order of acute toxicity via the oral (Category ID), dermal (Category IV) and inhalation (Category
IV) routes of exposure. It is a moderate eye and dermal irritant (Category ID) and is also a dermal
sensitizer.
Table 3. Acute Toxicity Profile for Occupational Exposure to Cycloate.
Guideline
Number
870.1100
(§81-1)
870.1200
(§81-2)
870.1300
(§81-3)
870.2400
(§814)
870.2500
(§81-5)
870.2600
(§81-6)
Study Type
Acute Oral Toxicity
(Rat)
Acute Dermal
Toxicity (Rabbit)
Acute Inhalation
Toxicity (Rat)
Acute Eye Irritation
(Rabbit)
Acute Dermal
Irritation
Acute Dermal
Sensitization
MRIDNo.
00132791
(Ro-Neet 6-E)
00132791
(Ro-Neet 6-E)
00132792
(Ro-Neet 6-E)
00132791
(Ro-Neet 6-E)
00132791
(Ro-Neet 6-E)
41729901
(Cycloate 98% TGAI)
Results
LD50= 3,250 mg/kg(cT)
LD50 = 4,175 mg/kg(?)
LD50 >5,000 mg/kg
LC50 >5.03 mg/L
Moderate eye irritant.
Moderate dermal irritant.
Cycloate is a dermal sensitizer.
Toxicity
Category
III
IV
IV
III
m
Not
Applicable
Subchronic Toxicity: There are no subchronic oral toxicity studies in the rodent or dog
identified in the data base for cycloate. However, the chronic oral studies in the rodent and dog
(MRIDs 00077787, 00137735 and 40458401) provided frequent monitoring of clinical signs and
interim measurements of body weights, food consumption, hematology, clinical chemistry and
urinalysis, and the results provided insight into potential subchronic effects. In addition, a special 27-
day oral neurotoxicity study and a subchronic oral neurotoxicity study (90-day) in the rat are
available. Also, two subchronic inhalation toxicity studies in the rat have been conducted.
Developmental Toxicity: The data base for developmental toxicity is considered complete. The
available data provided no indication of increased susceptibility (quantitative or qualitative) of rats or
rabbits to in utero and/or post-natal exposure to cycloate.
Reproductive Toxicity: The data base for reproductive toxicity is considered complete. In a 2-
generation reproduction study (MRTD 41691901), cycloate was administered to rats at dose levels of
0, 2.5, 20 and 50 mg/kg/day. The parental systemic LOAEL is 20 mg/kg/day based on decreased pup
body weight gain, decreased food consumption and histological findings in the nervous system
(mineralization of the brain, sacral spinal cord white matter degeneration). The parental systemic
NOAEL is 2.5 mg/kg/day. In the 3-generation reproduction study in the rat (MRID 00132795), the
7
-------
parental systemic LOAEL is 24 mg/kg/day, based on decreased pup body weight/body weight gains.
The parental systemic NOAEL is 8 mg/kg/day.
Chronic Toxicity: The data base for chronic toxicity is considered complete. In one combined
chronic toxicity/carcinogenicity rat study (MRID 00137735), spinal nerve axonal atrophy and
femoral nerve alterations were observed in females. The LOAEL is 3.1 mg/kg/day and the NOAEL
is 0.5 mg/kg/day. In another combined chronic toxicity/carcinogenicity study in the rat (MRID
00077787), decreased cholinesterase activity (females) and neuromyopathy (cycloate can cause
damage to various nerves and muscles) of the sciatic nerve and associated muscles (both sexes) were
noted at the LOAEL of 8.0 mg/kg/day. A NOAEL was not achieved in this study. Dogs
administered 50 mg/kg/day in the diet displayed clinical signs (loose stool), clinical chemistry
alterations (increased alkaline phosphatase activity, decreased blood urea nitrogen) and histological
findings in the liver (hepatocellular hypertrophy, portal tract fibrosis, central vein active-chronic
inflammation), kidney (papillopathy) and adrenal gland (cortical hyperplasia and/or hypertrophy).
Carcinogenicity: The data base for carcinogenicity is considered complete. There was no
evidence of carcinogenic potential of cycloate in the rat or mouse. Based on the available data,
cycloate has been classified as "not likely to be carcinogenic in humans ."
Mutagenicity: Cycloate was negative in a reverse gene mutation assay in bacteria, in
mammalian cell cytogenetics assays (chromosome aberration in human lymphocytes) and in a mouse
bone marrow micronucleus assay. In mammalian cell cytogenetics assays (chromosome aberration
and sister chromatid exchange - L5178Y mouse lymphoma cells), significant clastogenic responses at
levels of high cytotoxicity and significant induction of SCEs were observed at the majority of assayed
doses, which extended into the cytotoxic range. It was weakly mutagenic in the presence of S9
activation over a narrow range of severely cytotoxic levels in a mammalian cell gene mutation assay
at the TK+/" locus in mouse lymphoma cells.
Neurotoxicity: Mammalian neurotoxicity studies for cycloate have been conducted. Acute,
subchronic, chronic and reproductive toxicity and special neurotoxicity studies have demonstrated
central nervous system (CNS) and peripheral nervous system (PNS) neuropathological findings in
several species. Effects include cholinergic signs, abnormalities in gait and posture in the hind legs,
decreased hind limb grip strength, muscle atrophy and lesions in the brain (including specific regions
such as medulla and the dentate gyrus/pyriform cortex), spinal cord, spinal nerve, sciatic nerve, sural
nerve and tibial nerve. Inhibition of cholinesterase and/or neurotoxic esterase activities has also been
noted in several toxicity studies.
A developmental neurotoxicity study (DNT), including cholinesterase measures, in the rat has
been identified as a data gap.
Dermal Absorption: A dermal absorption study in the rat (MRIDs 00164351, 40229701 and
43712502) indicated a 16% absorption of cycloate at 10 hours exposure.
-------
Metabolism: Metabolism studies were conducted in the rat and the mouse (MRID 00132796).
The predominant urinary metabolite identified in the rat and the mouse was N-ethylcyclohexylamine.
There was no significant bioaccumulation of cycloate and/or its metabolites. Results indicated that
cycloate was rapidly absorbed following oral administration with half-times suggesting the presence
of a small population of slow metabolizers and/or excreters. The percent absorbed ranged from
approximately 61% to 68%. Tissue radioactivity was low at 192 hours with most of the activity
remaining in the liver and kidneys. Urinary excretion was the primary route of elimination. The
predominant urinary metabolite identified was N-ethylcyclohexylamine.
b. FQPA Safety Factor
EPA has determined that a Database Uncertainty Factor (UFDB) of lOx is needed to account for
the lack of the DNT when assessing acute (single dose) exposure scenarios since the available data
provide no basis to support reduction or removal of the default lOx factor. In addition, no special
FQPA safety factor is needed since there are no residual uncertainties for pre- and/or post-natal
toxicity. A Ix FQPA special safety factor for sensitivity in infants and children is to be applied across
all of the risk assessments, except for occupational assessments.
c. Population Adjusted Dose
Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute
and chronic dietary assessments, the risk is expressed as a percentage of a maximum acceptable dose
(i.e., the dose which will result in no unreasonable adverse health effects). This dose is referred to as
the Population Adjusted Dose (PAD). Dietary risk is characterized in terms of the PAD, which
reflects the Reference Dose (RfD), either acute or chronic, that has been adjusted to account for the
FQPA Safety Factor. A risk estimate that is less than 100% of the PAD is not of concern to the
Agency.
1) Acute PAD
For setting the aRfD, a LOAEL of 200 mg/kg/day was selected from the acute neurotoxicity
study in rats. A NOAEL was not identified. There is a concern for potential developmental
neurotoxicity resulting from exposure to cycloate. A UFDB of lOx is needed to account for the lack of
a DNT study when assessing acute (single dose) exposure scenarios. As discussed in Section
IH.A.l.b, no special FQPA safety factor is needed since there are no residual uncertainties for pre-
and/or post natal toxicity. Thus the total uncertainty factor (UF) is 3,000 (lOx for interspecies
extrapolation; lOx for intraspecies variation; 3x for the lack of a NOAEL; and lOx to account for the
lack of a DNT study). The aPAD was set at 0.066 mg/kg/day.
-------
2) Chronic PAD
For setting the cRfD, a LOAEL of 3.1 mg/kg/day was selected from the combined toxicity/
carcinogenicity study in rats. The NOAEL in this study was 0.5 mg/kg/day. An uncertainty factor of
100 (lOx for interspecies extrapolation; lOx for intraspecies variation; and a Ix special FQPA safety
factor) was calculated. The cPAD was set at 0.005 mg/kg/day.
d. Exposure Assumptions
The acute and chronic dietary exposure/risk analysis for cycloate was conducted using the
Dietary Exposure Evaluation Model-Food Commodity Intake Database (DEEM-FCID™, Version
1.30), which incorporates food consumption data from the U.S. Department of Agriculture's
(USDA's) Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998.
The CSFn data are based on the reported food consumption by more than 20,000 individuals over
two nonconsecutive survey days. For the acute and chronic exposure assessment, consumption data
are averaged for the entire U.S. population and within population subgroups. Exposure estimates are
reported in mg/kg body weight/day, and risk is expressed as a percent of the acute or chronic PAD.
The Agency's Metabolism Assessment Review Committee (MARC) has reviewed the cycloate
toxicology and metabolism data (meeting date of November 5, 2003) and has concluded that cycloate
and its cis- + trans- 3-hydroxycycloate (3HC) and cis + trans- 4-hydroxycycloate (4HC) metabolites
are the residues of concern for risk assessment. Assessments for cycloate were performed using
tolerance level residues at the screening Tier 1 level. Because these Tier 1 assessments were based
upon tolerances, exposure is estimated for residues of cycloate and its 3HC and 4HC metabolites.
Although percent crop treated data were available, they were not necessary to refine the assessment.
e. Dietary (Food) Risk Assessment
1) Acute Dietary Risk
Acute dietary risk is calculated considering what is eaten in one day and maximum, or high-end
residue values in food. A risk estimate that is less than 100% of the acute population adjusted dose
(aPAD), the dose at which an individual could be exposed on any given day and no adverse health
effects would be expected, does not exceed the Agency's level of concern. The aPAD is the acute
dietary reference dose (aRfD) adjusted for the FQPA Safely Factor.
For cycloate, the acute dietary (food only) risk does not exceed the Agency's level of concern
for the U.S. population and all subgroups, including infants and children, using highly conservative
assumptions. The acute dietary (food only) risk estimate is 1.1% of the aPAD at 95th percentile of
exposure, for the most highly exposed population subgroup, children aged 3-5 years. Exposure and
risk estimates are summarized in Table 4.
10
-------
2) Chronic Dietary Risk
Chronic dietary risk is calculated by using the average consumption value for food and average
residue values on those foods. A risk estimate that is less than 100% of the chronic population
adjusted dose (cPAD), the dose at which an individual could be exposed over the course of a lifetime
and no adverse health effect would be expected, does not exceed the Agency's level of concern. The
cPAD is the chronic dietary reference dose (cRfD) adjusted for the FQPA Safety Factor.
The chronic dietary (food only) risk estimates from exposures to cycloate in food do not exceed
the Agency's level of concern (i.e., they are less than 100% of the cPAD) for the U.S. population and
all subgroups using highly conservative assumptions. The chronic dietary (food only) risk estimate is
5.5% of the cPAD for the most highly exposed population subgroup, children aged 3-5 years.
Exposure and risk estimates are summarized in Table 4.
Table 4. Summary of Dietary Exposure and Risk for Cycloate.
Population Subgroups
U.S. General Population
All Infants (<1 year old)
Children (1-2 years old)
Children (3-5 years old)
Children (6-12 years old)
Youth (13-19 years old)
Adults (20-49 years old)
Females (13-49 years old)
Seniors (50+ years old)
Acute Dietary
(95th Percentile)
Dietary Exposure
(mg/kg/day)
0.000408
0.000672
0.000720
0.000755
0.000556
0.000307
0.000261
0.000278
0.000254
%aPAD
<1.0
1.0
1.1
1.1
<1.0
<1.0
<1.0
<1.0
<1.0
Chronic Dietary
Dietary Exposure
(mg/kg/day)
0.000119
0.000172
0.000259
0.000277
0.000205
0.000103
0.000083
0.000088
0.000105
% cPAD
2.4
3.4
5.2
5.5
4.1
2.1
1.7
1.8
2.1
For more information on the dietary risk assessment, please refer to the Dietary Exposure and
Risk Analysis sections of the "Cycloate In/On Spinach, Garden Beets, Sugarbeets and Swiss Chard.
Health Effects Division (HED) Risk Assessment," dated January 28, 2004.
11
-------
2. Dietary Risk from Drinking Water
Drinking water exposure to pesticides can occur through ground and surface water
contamination. In assessing drinking water risks, EPA considers acute (one day), chronic (long-term)
and cancer (lifetime) exposure, and uses either modeling or actual monitoring data if available, to
estimate those risks. To determine the maximum allowable risk contribution from water, EPA first
looks at how much of the overall allowable risk is contributed by food and then calculates a "drinking
water level of comparison" (DWLOC) to determine whether modeled or monitoring exposure
estimates exceed this level. The DWLOC represents the maximum contribution to the human diet
that may be attributed from residues of a pesticide in drinking water after food exposure is subtracted
from the aPAD or cPAD. Risks from drinking water are assessed by comparing the DWLOC to
estimated environmental concentrations (EECs) in both surface and ground water. EECs that are less
than the DWLOC are not of concern.
The Agency has determined that cydoateper se is the residue of concern in drinking water.
Fate studies indicate that the major dissipation route for cycloate is volatilization, but when applied to
soil in a manner to prevent volatilization, cycloate is moderately persistent and is expected to be
moderately mobile. In various limited water monitoring studies, mostly in high use areas, cycloate
was occasionally detected in ground water, but never in excess of 2 parts per billion (ppb). These
data support the modeling conclusion that risks are below the Agency's level of concern (LOG) for all
population subgroups. There is no information on the effects of water treatment on cycloate or any
degradate.
According to the U.S. Geological Survey (1992 pesticide annual use data), about 94% of
cycloate use was on sugarbeets, so EPA's water analysis focused on this use. The Minnesota
sugarbeet use pattern was selected for both the surface and ground water assessments as this is
expected to represent a reasonable worst case situation, that is, greatest potential for drinking water
contamination. The maximum use rate on sugarbeets is 4 Ibs. a.i./acre. One application per
growing season (spring or fall) is allowed.
a. Surface Water
Modeling: The Tier II screening models, Pesticide Root Zone Model and Exposure Analysis
Modeling System (PRZM/EXAMS), with the Index Reservoir and Percent Crop Area adjustment
(IR-PCA PRZM/EXAMS) were used to estimate cycloate residues in surface water used for drinking
water. These screening models provide more refined, less upper-bound assumptions.
For cycloate, the acute (peak) and chronic (90th percentile) surface water EECs are 52 ppb and
10 ppb, respectively. The modeled EECs are less than the acute and chronic DWLOCs calculated for
the U.S. General Population (2,296 ppb and 171 ppb, respectively) and all population subgroups.
Acute DWLOCs were smallest (and were almost identical) for the population subgroups: infants <1
year of age, children aged 1-2 years, children aged 3-4 years and children aged 6-12 years. For these
12
-------
subpopulations, available acute DWLOC values ranged from 652 to 654 ppb, which were still large
compared to the acute EECs. Similarly, chronic DWLOCs were smallest (and were almost identical)
for the population subgroups: infants <1 year of age, children aged 1-2 years, children aged 3-4 years
and children aged 6-12 years. For these subpopulations, the chronic DWLOC values ranged from 47
to 48 ppb, all large when compared to the chronic EECs. Therefore, aggregate exposures to cycloate
in food and water, both acute and chronic, were below the Agency's LOG for all population
subgroups, including children (3-5 years), the population subgroup with the highest risk estimate (see
Tables 5 & 6).
Monitoring: The state of Minnesota does not monitor for cycloate in the Red River of the
North Valley (M. Zabel, Minnesota Department of Agriculture, November 2, 2000). North
Dakota also does not monitor for cycloate (N. Bardeson, North Dakota Health Department,
October 31, 2000). California has not conducted any monitoring studies for cycloate in surface
water (K. Starner, California Department of Pesticide Regulation, October 31, 2000).
The only surface water monitoring information available is from the state of Washington's
Department of Ecology where they monitored for cycloate (parent only) in 10 creeks in the Puget
Sound area in April to May of 1998 (G. Bortleson and J. Ebbert, USGS WRIR 00-4118). No
cycloate was detected (limit of detection is >0.14 ppb). The sampling locations did not appear to be
in sugarbeet growing areas. However, garden beet and spinach seed production are located in that
area.
b. Ground Water
Modeling: Estimated ground water concentrations are based on the Screening Concentration in
Ground Water (SCI-GROW) model, which is a Tier I assessment that provides a high-end estimate.
The SCI-GROW model generates a single EEC value of pesticide concentration in ground water used
for drinking water and provides a ground water screening concentration for use in determining
potential risk to human health from drinking water contaminated with a pesticide. Further, this EEC
is used in assessments of both acute and chronic dietary risk. It is not unusual for the ground water
EEC to be significantly lower than the surface water EECs.
For cycloate, the ground water EEC is 1 ppb. Since the modeled EEC is less than the aggregate
DWLOCs calculated for the U.S. General Population and all population subgroups (2,296 ppb and
171 ppb, respectively), aggregate exposure to cycloate in food and drinking water from ground water
sources, both acute and chronic, are below the Agency's LOG for all population subgroups, including
children (3-5 years), the population subgroup with the highest risk estimate (see Tables 5 & 6).
Monitoring: Several states (Idaho, Michigan and Oregon), where cycloate is used, have
monitored for cycloate (parent only) in ground water. The Idaho Department of Agriculture has
sampled for cycloate in 45 wells in the Burley Perched Aquifer in Minidoka county, a sugarbeet
growing area since 1998. Cycloate was detected in 1 well in 1999 at a concentration of 0.36 ppb.
13
-------
Cycloate was not detected in 2000. In Michigan, 280 ground water samples from the 11 counties
with the highest sugarbeet production were analyzed over a period of 8 years, with no detections
of cycloate (personal communication with M. Schwartz, MI Department of Agriculture,
November 13, 2000). The samples were taken from domestic wells, bulk agricultural chemical
storage facilities and dairies.
The state of Oregon maintains a data base of water quality analyses called the Laboratory
Analytical Storage and Retrieval Database (LASAR). For cycloate, the data base contains data
for 615 ground water samples taken from 266 discrete locations (1990 to the present), from
northern Malheur County, the lower Umatilla Basin, Clatsop Plains and the Ontario area (Malheur
county). Malheur county is a heavy use area for cycloate (more than 4.745 Ibs. a.i. per square
mile in 1992 (USGS 1992 annual use map). The USGS map also indicates that cycloate is used
in Umatilla county and possibly in Clatsop county. In 1998, only 1 detection of cycloate was
reported in a City of Vale (North Malheur county) well 1.8 ppb.
Table 5. Comparison of Calculated Acute DWLOCs and EECs for Cycloate.
Population Subgroup
U.S. Population
All Infants (<1 year)
Children (1-2 years)
Children (3-5 years)
Children (6-12 years)
Youth (13-19 years)
Adults (20-49 years)
Females (13-49 years)
Seniors (50+ years)
aPAD
(mg/kg/day)
0.066
0.066
0.066
0.066
0.066
0.066
0.066
0.066
0.066
Acute Food
Exposure
(mg/kg/day)
0.000408
0.000672
0.000720
0.000755
0.000556
0.000307
0.000261
0.000278
0.000254
Maximum Acute
Water Exposure1
(mg/kg/day)
0.065592
0.065328
0.065280
0.065245
0.065444
0.065693
0.065739
0.065722
0.065745
Ground
Water
EEC1
(Ppb)
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
Surface
Water
EEC2
(Ppb)
52
52
52
52
52
52
52
52
52
Acute
DWLOC
(Ppb)
2,296
653
653
652
654
1,971
2,301
1,972
2,301
Maximum water exposure (mg/kg/day) = aPAD (mg/kg/day) - food exposure (mg/kg/day)
Sugarbeet was used.
14
-------
Table 6. Comparison of Calculated Chronic DWLOCs and EECs for Cycloate.
Population Subgroup
U.S. Population
All Infants (<1 year)
Children (1-2 years)
Children (3-5 years)
Children (6-12 years)
Youth (13-19 years)
Adults (2049 years)
Females (1349 years)
Seniors (50+ years)
cPAD
(mg/kg/day)
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
Chronic
Food
Exposure
(mg/kg/day)
0.000119
0.000172
0.000259
0.000277
0.000205
0.000103
0.000083
0.000088
0.000105
Maximum
Chronic Water
Exposure1
(mg/kg/day)
0.004881
0.004828
0.004741
0.004723
0.004795
0.004897
0.004917
0.004912
0.004895
Ground
Water
EEC
(Ppb)
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
Surface
Water
EEC
(Ppb)
10
10
10
10
10
10
10
10
10
Acute
DWLOC
(Ppb)
171
48.3
47.4
47.2
48.0
147
172
147
171
1 Maximum water exposure (mg/kg/day) = cPAD (mg/kg/day) - food exposure (mg/kg/day)
For more information on drinking water risks and the calculations of the DWLOCs, see the
Water Exposure section of the "Cycloate In/On Spinach, Garden Beets, Sugarbeets and Swiss Chard.
Health Effects Division (HED) Risk Assessment," dated January 28, 2004 and the Drinking Water
Assessment section of the "Cycloate: Reregistration Eligibility Document Science Chapter, PC
Number 041301, Environmental Fate and Effects Division (EFED)," dated August 23, 2002.
3. Residential and Other Nonoccupational Exposure
Cycloate is not registered for any residential (home/garden) use, nor is it used in or around
public buildings, schools or recreational areas where children or the others might be exposed. Thus,
there is no residential exposure to aggregate with the dietary exposure.
4. Aggregate Risk
The aggregate risk assessment for cycloate integrates the assessments conducted for food and
drinking water exposure only since there are no residential uses for cycloate. For aggregate exposure,
the Agency calculates a DWLOC which represents the maximum allowable exposure through
drinking water after considering the dietary exposure to cycloate. If the EECs are less than the
DWLOCs, the Agency does not have concern for aggregate exposure. No population subgroup
exceeded EPA's level of concern for either acute or chronic dietary exposure to cycloate based upon
aggregated exposure to food plus water. Given current uses, the Agency has no risk concerns for
aggregate exposure to cycloate through food and water.
15
-------
5. Occupational Risk
People can be exposed to a pesticide while working through mixing, loading and application
activities and when re-entering a treated site. Occupational risks are estimated in terms of Margins of
Exposure (MOEs). An MOE is the ratio of the NOAEL to the (occupational) exposure. Thus, an
MOE of 10 means the NOAEL is 10 times the estimated exposure. Generally, for cycloate, MOEs
greater than 100 for dermal exposure and 300 for inhalation exposure are not of concern. For workers
entering a treated site, MOEs are calculated for each day after application to determine the minimum
length of time required before workers can safely reenter.
Occupational risk is assessed for exposure of mixers, loaders and applicators (termed "handler"
exposure) and for exposure following application (termed "post-application" or worker exposure).
Handler risk is based on combining both dermal and inhalation exposures. Worker risk is assessed
for activities such as scouting, irrigating, mechanical weeding and hand harvesting and is based
primarily on dermal exposure.
The Agency has determined that there is a potential for short- and intermediate-term exposures
in occupational settings from handling cycloate products during the application process (i.e.,
mixer/loader, applicator and mixer/loader/applicator). As a result, risk assessments have been
completed for occupational handlers. Additionally, short-term exposures are anticipated from
entering previously treated areas; however, since cycloate is incorporated into the soil either
immediately or within a few hours after application, post-application exposures are expected to be
negligible as compared to handler exposure.
An overview of the assumptions and calculations of potential risks to workers can be found in
the "Cycloate: Occupational and Residential Exposure Assessment and Recommendations for the
Reregistration Eligibility Decision (RED) Document," dated October 9, 2003 and the Occupational
Exposure section of the "Cycloate In/On Spinach, Garden Beets, Sugarbeets and Swiss Chard.
Health Effects Division (HED) Risk Assessment," dated January 28, 2004.
a. Occupational Toxicity
The toxicological endpoints that were used to determine short- (1 to 30 days) and intermediate-
term (1 to 6 months) dermal and inhalation risk estimates were based upon separate dermal and
inhalation studies, as reported by the Agency's Hazard Identification Assessment Review Committee
(fflARC) on September 25, 2003. A LOAEL of 0.25 mg/kg/day, from a 21-day inhalation study in
rats (MRID 43552101), is used for inhalation risk estimates. The dose selection is based on moderate
respiratory epithelial cell hyperplasia of the nasal cavity in female rats and the weight-of-evidence in
four separate studies. A NOAEL of 10 mg/kg/day, from a 21-day dermal study in rats (MRIDs
42090305 and 43323801), is used for dermal risk estimates. The dose selection is based on reduction
in body weight gain in male rats.
16
-------
Although the inhalation risk assessment for occupational exposures was based on respiratory
effects, neurotoxic effects were also seen in the same rodent toxicity study. The risk assessment
based on the respiratory endpoint is protective of all other effects seen in the study. In effect, the
more sensitive respiratory endpoint used in the inhalation risk assessment is protective of potential
neurotoxic effects. Dermal and inhalation risk estimates cannot be aggregated, because the
endpoints/effects are different. Long-term (6 months to year-round) handler exposures are not
anticipated from cycloate.
Cycloate has a low order of acute toxicity via the oral (Category III), dermal (Category IV) and
inhalation (Category IV) routes of exposure. It is a moderate eye and dermal irritant (Category HI)
and is also a dermal sensitizer. Table 7 summarizes the toxicity endpoints used in the occupational
risk assessment.
Table 7. Summary of Cycloate Occupational Toxicity Endpoints.
Exposure Scenario
Dermal (both short- and
intermediate-term)
Inhalation (both short- and
intermediate-term)1
Dose
(NOAEL)
10
mg/kg/day
Not
established
Dose
(LOAEL)
50
mg/kg/day
0.25
mg/kg/day
Endpoint
Decreased body weight gain.
Short-term — minimal-to-moderate respiratory
epithelial cell hyperplasia of the nasal cavity of
female rats.
Intermediate-term — increased incidence and
severity of hypertrophy and/or hyperplasia of the
anterior nasal epithelium.
Study
21 -day rat
dermal
21 -day rat
inhalation
1 For occupational exposure: short-term (1 to 30 days) and intermediate-term (1 to 6 months) inhalation exposure risk
assessments, an MOE of 300 is required. This is based on the conventional uncertainty factor of lOOx (lOx for intraspecies
extrapolation and lOx for interspecies variation) and an additional 3x factor for the lack of a NOAEL.
b. Occupational Exposure
It is the Agency's standard practice to use surrogate data from the Pesticide Handlers Exposure
Database (PHED) Version 1.1 to assess handler exposures for regulatory actions when chemical-
specific monitoring data are not adequate, acceptable or available. PHED uses standard assumptions
about average body weight, work day, daily areas treated, volume of pesticide used, etc. The
exposure factors (e.g., body weight, amount treated per day, protection factors, etc.) are all standard
values used by the Agency, and the PHED unit exposure values are the best available estimates of
exposure.
For cycloate, surrogate data from PHED were used to assess handler exposures. Use of the
PHED unit exposures for risk assessment is a very conservative approach, because much of the data
supporting these unit exposures are derived from passive dosimetry methods and from chemicals that
17
-------
are not very volatile. Therefore, the resulting risk estimates using these PHED unit exposures should
be considered very conservative, and may actually be over-estimates.
Guideline handler studies were not submitted for cycloate. Instead, the registrant submitted a
cycloate biomonitoring handler (mixer/loader/applicator) exposure study. Biological monitoring was
selected as the monitoring method for this study because "cycloate is a volatile pesticide and is not a
suitable compound for passive dosimetry." This study determined the rate of volatilization of RO-
NEET® 6-E on two types of dosimetry patches indicating that the half-lives of cycloate were 3.1
hours for gauze patches and 3.2 hours for t-shirt (cotton) patches.
The biomonitoring study was reviewed and found to be unacceptable due to some inadequacies
and inconsistencies in the data; however, the data compiled and generated from the biomonitoring
study are useful in the estimation, assessment and characterization of risks to handlers of cycloate
since the results from the biomonitoring study are within the same order of magnitude as the unit
exposure estimates generated by using the PHED data and assuming maximum application rates.
Specifically, from the biomonitoring study, the dermal absorbed dose of cycloate for all test subjects
ranged from 0.00001 to 0.074 mg/kg/day (mean = 0.011 mg/kg/day), and the inhalation exposure
ranged from 0.23 to 45.63 |ig/kg/day (mean = 5.16 |ig/kg/day). Short-term baseline estimates from
PHED for dermal exposure range from 0.00008 to 0.11 mg/kg/day, and for inhalation exposure from
5.1to36.0|ig/kg/day.
Anticipated use patterns, application methods and range of application rates were derived from
current labeling. Application rates are the maximum application rates determined from EPA
registered labels. Cycloate is typically applied using groundboom equipment. The maximum labeled
application rate is 4 Ibs. a.i./acre. Typical (average) application rates are similar on garden beets,
spinach and sugarbeets, ranging from 2 to 3 Ibs. a.i./acre.
Occupational handler exposure assessments are conducted using different levels of protection.
The Agency typically evaluates all exposures with minimal protection and then considers additional
protective measures using a tiered approach (going from minimal to maximum levels of protection) in
an attempt to determine the protection needed to reduce risks to below the Agency's level of concern
(LOG). The lowest tier is represented by the baseline exposure scenario (i.e., single layer clothing,
socks, and shoes), followed by, if MOEs are still of concern, increasing levels of risk mitigation such
as personal protective equipment (PPE) and engineering controls.
The cycloate label requires the use of a closed system or the following PPE for mixers/loaders
and applicators: long-sleeved shirts, long pants, shoes plus socks and chemical-resistant gloves. The
label specifies a 12 hour REI for all application methods. California (CA) requires additional worker
protection. Mixers/loaders in CA must either use closed systems and PPE or chemical-resistant
clothes over work clothes and a full face respirator. Applicators in CA must either use an enclosed
cab or wear overalls over work clothes and wear a half-face respirator. CA also limits the amount of
18
-------
cycloate that can be handled per day to 93 gallons (560 Ibs. a.i.) per mixer/loader or applicator. The
levels of protection that formed the basis for calculations of exposure from cycloate activities include:
Baseline: Long-sleeved shirt and long pants, shoes and socks.
Minimum PPE: Baseline + chemical-resistant gloves and dust/mist respirator.
Maximum PPE: Baseline + chemical-resistant gloves, double layer of clothing and a
NIOSH-approved respirator with an organic-vapor removing cartridge.
Engineering controls: Engineering controls such as a package-based system (e.g., water-
soluble packaging for wettable powders) or other closed mixing/ loading
systems and enclosed cab or truck. Some engineering controls are not
applicable for certain scenarios (e.g., for handheld application methods,
there are no known devices that can be used to routinely lower the
exposures).
c. Occupational Handler Risk Summary
The Agency has determined that there are potential exposures to handlers during the usual use
patterns associated with cycloate. The anticipated use patterns and current labeling of cycloate
indicate seven major occupational handler exposure scenarios (11 scenarios total) based on the types
of equipment and techniques that potentially can be used to make cycloate applications. Five of these
scenarios were assessed. Scenario 6 (applying sprays with soil injection equipment with an
open/enclosed cab) and Scenario 7 (applying impregnated dry bulk fertilizers with tractor drawn
spreader) were not assessed because exposure data were not available for these two scenarios and
exposure through these scenarios is adequately covered by other scenarios. Groundboom PHED
values were used as surrogates for the soil injection technique of Scenarios 6a and 6b. Because
dermal and inhalation endpoints and uncertainty factors differ, separate dermal and inhalation
exposure assessments have been conducted. The seven major occupational handler exposure
scenarios were identified as follows:
Scenario (la) open mixing/loading of emulsifiable concentrate (EC) liquid formulation for
chemigation;
• Scenario (Ib) closed system mixing/loading of EC liquid formulation for chemigation;
• Scenario (2a) open mixing/loading of EC liquid formulation for groundboom or soil injection
applications;
Scenario (2b) closed system mixing/loading of EC liquid formulation for groundboom or soil
injection applications;
Scenario (3) closed system mixing/loading/incorporating of EC liquid formulation onto dry
bulk fertilizers (on-farm technique);
• Scenario (4) closed system mixing/loading/incorporating of EC liquid formulation with liquid
fertilizers (on-farm technique);
19
-------
• Scenario (5a) applying sprays with groundboom equipment with an open cab;
• Scenario (5b) applying sprays with groundboom equipment with an enclosed cab;
• Scenario (6a) applying sprays with soil injection equipment with an open cab;
Scenario (6b) applying sprays with soil injection equipment with an enclosed cab; and
Scenario (7) applying impregnated dry bulk fertilizers with tractor drawn spreader.
MOE estimates were calculated for all scenarios at baseline, minimum PPE, maximum PPE and
engineering control level exposures if necessary. Results of exposure and risk estimates for each
occupational handler exposure scenario are presented in Table 8. For more information on the
occupational risks, see the calculations in the occupational exposure section of the "Cycloate In/On
Spinach, Garden Beets, Sugarbeets and Swiss Chard. Health Effects Division (HED) Risk
Assessment," dated January 28, 2004.
20
-------
Table 8. Summary of Short-/Intermediate-Term Occupational Exposure Scenarios/Risk Estimates for Cycloate Handlers.
Scenario No.
Crop/Use
Application
Rate1
(Ibs. a.L/acre)
Daily
Acreage
Treated2
Engineering
Controls
Dermal UE3
(mg/lb. a.L)
Engineering
Controls
Inhalation UE3
(mg/lb. a.L)
Dermal Dose4
(mg/kg/day)
Inhalation Dose5
(mg/kg/day)
Dermal
MOE6
(Target
MOE=100)
Inhalation
MOE7
(Target
MOE=300)
Mixer/Loader
(1) Closed Mixing/Loading of EC Liquid Formulation
for Chemigation Application
(2) Closed Mixing/Loading of EC Liquid Formulation
for Groundboom Application
(3) Closed Mixing/Loading & Impregnation of EC
Liquid Formulation onto Dry Bulk Fertilizers
sugarbeets
garden beets
spinach
sugarbeets
sugarbeets
garden beets
garden beets
spinach
sugarbeets
sugarbeets
4
4
4
4
4
4
4
4
4
4
350
350
350
200
80
200
80
80
200
80
An
(4) Applying Liquids by Groundboom with Enclosed
Cabs
(5) Applying Impregnated Dry Bulk Fertilizers with
Enclosed Cabs
sugarbeets
sugarbeets
garden beets
garden beets
spinach
sugarbeets
sugarbeets
4
4
4
4
4
4
4
200
80
200
80
80
200
80
0.0086
0.0086
0.0086
0.0086
0.0086
0.0086
0.0086
0.0086
N/A
N/A
8.3E-5
8.3E-5
8.3E-5
8.3E-5
8.3E-5
8.3E-5
8.3E-5
8.3E-5
1.7E-4
1.7E-4
0.172
0.172
0.172
0.0983
0.0393
0.0983
0.0393
0.0393
N/A
N/A
0.00166
0.00166
0.00166
0.000949
0.000379
0.000949
0.000379
0.000379
0.00194
0.000777
58
58
58
102
250
102
250
250
N/A
N/A
150
150
150
260
660
260
660
660
130
320
vlicator
0.0051
0.0051
0.0051
0.0051
0.0051
0.002
0.002
4.3E-5
4.3E-5
4.3E-5
4.3E-5
4.3E-5
2.2E-4
2.2E-4
0.0583
0.0233
0.0583
0.0233
0.0233
0.0229
0.0091
0.000491
0.000197
0.000491
0.000197
0.000197
0.00252
0.001
170
430
170
430
430
440
1,100
510
1,300
510
1,300
1,300
99
250
Application rates are based on the maximum application rates listed on EPA registered labels for cycloate.
Amount handled per day values are based on HED Exposure SAC Standard Operating Procedure # 009 "Standard Values for Daily Acres Treated in Agriculture," revised June 23,2000.
Unit Exposure (UE): Unless otherwise noted, dermal and inhalation unit exposure values from PHED v. 1.1 Surrogate Exposure Guide, August 1998. Engineering controls for mixers/loaders consist of closed
systems or organic vapor respirator and enclosed cabs for applicators.
Dermal dose = dermal unit exposure (mg/lbs. a.i.) x application rate (Ibs. a.i./acre) x amount handled per day (acres/day) / body weight (70 kg).
Inhalation dose = inhalation unit exposure (mg/lbs. a.i.) x application rate (Ibs. a.i./acre) x amount handled per day (acres/day) / body weight (70 kg).
Short-/Tntermediate-term dermal MOE = NOAEL (10 mg/kg/day) / daily dermal dose (mg/kg/day). N/A= Not Applicable. Bolded MOEs have a risk concern at the engineering control level for corresponding
scenarios.
Short-/Tntermediate-term inhalation MOE = LOAEL (0.25 mg/kg/day) / daily inhalation dose (mg/kg/day). Bolded MOEs have a risk concern at the engineering control level for corresponding scenarios.
21
-------
The target MOE of 100 for dermal exposure was met or exceeded at either the maximum PPE
or engineering control levels for most of the short- and intermediate-term occupational exposure
scenarios for mixing, loading and applying cycloate to garden beets, spinach and sugarbeets.
In addition, the target MOE of 300 for inhalation exposure was met or exceeded at either the
maximum PPE or engineering control levels for a number of the short- and intermediate-term
occupational exposure scenarios for mixing, loading and applying cycloate to garden beets, spinach
and sugarbeets.
The dermal MOEs were less than the target MOE of 100 with maximum risk reduction
measures for the following occupational exposure scenario:
• Scenario (1) closed system mixing/loading of EC liquid formulation for chemigation
application to garden beets, sugarbeets and spinach at 350 acres at 4 Ibs. a.i./acre.
The inhalation MOEs were less than the target MOE of 300 with maximum risk reduction
measures for the following occupational exposure scenarios:
• Scenario (1) closed system mixing/loading of EC liquid formulation for chemigation
application to garden beets, sugarbeets and spinach at 350 acres at 4 Ibs. a.i./acre;
• Scenario (2) closed system mixing/loading of EC liquid formulation for groundboom or soil
injection applications to garden beets and sugarbeets at 200 acres at 4 Ibs. a.i./acre;
• Scenario (3) closed system mixing/loading and incorporating of EC liquid formulation onto dry
bulk fertilizers (on-farm technique) to sugarbeets at 200 acres at 4 Ibs. a.i./acre; and
Scenario (5) applying impregnated dry bulk fertilizers with enclosed cabs to sugarbeets at 80
and 200 acres at 4 Ibs. a.i./acre.
1) Post-Application Occupational Risk
Post-application exposures are expected to be negligible compared to handler exposures
because cycloate is applied to the soil and incorporated into the soil immediately or within a few
hours after application, or it is injected directly into the soil.
2) California Air Monitoring
In California, the Air Resources Board, at the request of the California Department of Pesticide
Regulation, conducted a study to determine the airborne concentrations of the pesticide cycloate.
This study was completed on October 15, 2001. Application monitoring was conducted in Imperial
County around the use of cycloate on sugarbeets. Ambient monitoring was conducted to coincide
with the use of cycloate on sugarbeets also in Imperial County.
22
-------
Of the 64 application samples collected, 10 were found to be above the estimated quantitation
limit (EQL) of 63.0 ng/sample for cycloate, 29 sample results were equal to or above the method
detection limit (MDL) of 12.6 ng/sample, 24 sample results were detected (above the MDL but below
the EQL), and 1 sample was invalidated due to a sampling problem. The highest cycloate
concentration was 500 ng/m3 during the third sampling period.
Of the 115 ambient samples collected, 27 were found to be above the EQL of 63.0 ng/sample
for cycloate, 43 sample results were below the MDL of 12.6 ng/sample, and 45 sample results were
detected (above the MDL but below the EQL). The highest cycloate concentration was 220 ng/m3 at
the Heber Fire Department sampling site.
The application and ambient air concentrations from this study are well below the 21-day
inhalation LOAEL of 1.2 mg/m3 that was used in the Agency's occupational risk assessment. For
more detailed information associated with the airborne concentrations of the pesticide cycloate in
California, please refer to the "Final Report for the Application and Ambient Air Monitoring for
Cycloate," dated October 15, 2001. The complete report may be accessed through the Air Resources
Board's website at http://www.arb.ca.gov.
3) Human Health Incident Data
A review of human health incident data sources found only a few occupational incidents
involving cycloate and that relatively few incidents of illness have been reported due to cycloate.
Two incidents were due to workers not wearing label-specified PPE. A third incident was due to a
worker being too close to a tractor while it was involved in spraying the soil.
Cycloate was not reported to be involved in any human incidents on the list of the top 200
chemicals for which the National Pesticide Information Center (NPIC) received calls from 1984
through 1991, inclusively.
B. Environmental Risk Assessment
A summary of the Agency's environmental risk assessment is presented below. More detailed
information associated with the environmental risk from the use of cycloate may be found in the
"Cycloate: Environmental Fate and Effects Division (EFED) Reregistration Eligibility Document
Science Chapter," dated August 23, 2002. The complete environmental risk assessment is not
included in this RED, but may be accessed in the OPP Public Docket and on the Agency's website at
http://www.epa. sov/pesticides/reresistration/status. htm.
23
-------
1. Fate and Transport
Cycloate has a moderate solubility (75 to 95 mg/L at 25° C) and moderately high vapor
pressure (6.2 x 10"3 mm Hg at 25° C). Henry's Law constant is therefore a relatively high 1.85 x 10"5
atm-nrVmol. Combined, these properties indicate that cycloate has a pronounced tendency to
evaporate, especially from water or moist soil. In a laboratory volatilization study (MRID 41920602),
cycloate volatilized (as the parent) with an average 12.1% of the applied radioactivity volatilized after
4 hours and 13.4% after 25 hours. This behavior was also observed in the anaerobic aquatic
metabolism study (MRID 42997901), in which 50% of the parent compound volatilized over one
year. Label directions for cycloate require incorporation into the soil immediately after application to
slow down volatilization.
Cycloate is stable to hydrolysis and photolysis in water. However, a literature study (MRID
42541101) indicates that volatilized cycloate may have a short lifetime in air (5.2 hours) due to
reaction with hydroxyl radicals. Therefore, nontarget organisms are expected to be exposed to
cycloate via spray drift or volatility for several days after application.
Laboratory metabolism studies yielded half-lives of 43 days (aerobic soil, MRID 42812901),
68 days (anaerobic soil, Ace. 266125), and 192 days (anaerobic aquatic metabolism, MRID
42997901).
The one acceptable terrestrial field dissipation study (MRIDs 41582404-5), conducted in
Orange Cove, CA, yielded a soil half-life of 11 days in the upper 3 inches. A second field study was
compromised by irrigation of the study plot, which resulted in a failure to confirm the application
rate.
Laboratory studies show that cycloate tends to sorb to soil under dry conditions, and that the
sorption is not reversed if the soil is later flooded. However, if the soil is already flooded at the time
of application, cycloate is easily desorbed and then volatilized over time. Koc values (500 to 800
mL/g) indicate that cycloate is moderately mobile in soil.
Cycloate degradates in soil include the sulfoxide (which may revert to the parent under
reducing conditions) and N-ethylcyclohexylamine. Two sets of ring-hydroxy and ring-keto
degradates (the 4-hydroxy-, 4- keto-, 3-hydroxy- and 3-keto- degradates) are also formed in
laboratory studies. Other degradates seen in laboratory studies include N-cyclohexyl-N-
ethylformamide and N-ethyl-N-formyl-S-ethyl thiocarbamate.
In summary, cycloate applied to dry soil and immediately incorporated tends to remain sorbed
to the soil and dissipates with a half-life on the order of 1 to 2 months. Cycloate volatilizes from
moist soil if not immediately incorporated. Volatilized cycloate may be rapidly degraded by hydroxyl
24
-------
radicals in the air. Available monitoring data for surface and ground waters indicate that cycloate is
rarely detected in areas where it is used.
2. Ecological Risks
The Agency'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 nontarget organisms from the use of cycloate
products, the Agency calculates a Risk Quotient (RQ), which is the ratio of the EEC to the most
sensitive toxicity endpoint values, such as the median lethal dose (LD50) or the median lethal
concentration (LC50). The most sensitive species tested is chosen for these RQ calculations, but the
tests may not include the most sensitive species which may be exposed. These RQ values are then
compared to the Agency's LOCs which indicate whether a chemical, when used as directed, has the
potential to cause adverse effects on nontarget organisms. When the RQ exceeds the LOG for a
particular category, the Agency presumes a potential risk of concern to that category. The LOCs and
the corresponding potential risk presumptions are presented below in Table 9.
Table 9. LOCs and Associated Risk Presumptions.
IF...
THEN the Agency presumes...
Mammals and Birds
The acute RQ > LOG of 0.5
The acute RQ >LOC of 0.2
The acute RQ > LOG of 0. 1
The chronic RQ > LOG of 1
Potential acute risk
Potential risk that may be mitigated through restricted use
Potential acute effects may occur in Endangered Species
Potential chronic risk and chronic effects may occur in Endangered Species
Fish and Aquatic Invertebrates
The acute RQ > LOG of 0.5
The acute RQ > LOG of 0. 1
The acute RQ >LOC of 0.05
The chronic RQ > LOG of 1
Potential acute risk
Potential risk that may be mitigated through restricted use
Potential acute effects may occur in Endangered Species
Potential chronic risk and chronic effects may occur in Endangered Species
Risk Summary for Registered Uses of Cycloate
The uses of cycloate on garden beets, spinach and sugarbeets may cause adverse ecological
effects at the maximum application rate of 4 Ibs. a.i./acre. The potential risks include: (1) potential
chronic risk to birds, including federally listed endangered and threatened species; (2) potential
chronic risk to small mammals, including federally listed endangered and threatened species; (3)
potential risk to estuarine/marine fish and invertebrates; and (4) potential acute and chronic risk to
nontarget aquatic and terrestrial plants. Concern for potential chronic risk to small mammals is based
on reproductive effects seen in 2- and 3-generation rat reproduction studies. This concern extends to
the possibility of chronic effects in birds. These findings are based solely on EPA's screening level
assessment and do not constitute "may affect" findings under the ESA. The Agency does not have
25
-------
chronic data for birds and, in the absence of this data, we cannot preclude the possibility of chronic
risk to birds. The Agency intends to issue a DCI as part of this RED to require additional data for:
avian reproduction data; acute toxicity data for estuarine/marine animals; seedling emergence;
vegetative vigor; and aquatic plant growth to address areas of uncertainty. These data are expected to
confirm the conclusions of this screening level environmental risk assessment. In the absence of data,
there is much uncertainty in the environmental risk assessment for cycloate.
For a more detailed explanation of the ecological risks posed by the use of cycloate, please
refer to the Ecological Effects Hazard Assessment and Ecological Risk Assessment sections of the
"Cycloate: Environmental Fate and Effects Division (EFED) Reregistration Eligibility Document
Science Chapter," dated August 23, 2002.
a. Risk to Birds
1) Toxicity (Hazard) Assessment
Cycloate is considered practically nontoxic to birds on an acute oral basis since the LD50 value
is >2,150 mg/kg and the LC50 is >5,000 ppm (see Table 10). These values are greater than the highest
does tested (1,440 ppm). An LD50 is 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).
An LC50 is a statistically estimated measure (concentration) expected to be lethal to 50% of the test
population. Table 10 summarizes the data that support the acute toxicity endpoints used in assessing
the risks to birds.
Table 10. Acute Toxicity Endpoints for Birds.
Toxicity
Study
Test Species1
%a.L
Endpoint
Toxicity Category
MRIDor
Accession No.
Acute (Single dose by gavage)
Avian Oral
Northern Bobwhite Quail
(Colinus virginianus)
98.6
LD50 = >2, 150 mg/kg
Practically
Nontoxic
Ace. 072166
Subacute (Eight days of treated feed)
Avian Dietary
Mallard Duck
(Anas platyrhynchos)
Northern Bobwhite Quail
(Colinus virginianus)
96.8
LC50 = >5,395ppm
LC50 = >5,620 ppm
Practically
Nontoxic
42090306
00145554
1 Test species observed an additional three days while on untreated feed.
Currently, avian chronic toxicity tests have not been submitted to the Agency; therefore, it is
not possible to determine the chronic effects to birds from cycloate use. Avian reproductive studies
using the technical grade active ingredient (TGAI) are needed for cycloate because it is stable in the
environment to the extent that potentially toxic amounts may persist in animal feed especially
26
-------
preceding or during the breeding season and information derived from mammalian reproduction
studies indicates reproduction in terrestrial vertebrates may be adversely affected by the anticipated
use of the product.
2) Exposure and Risk
Exposure to birds will be primarily for edge-of-field habitats, where soil, water and food items
may become contaminated with cycloate by direct application, spray drift or volatilization. Since
cycloate is used before or at-planting, there are limited food items in the field; however, the animals
feeding in the field are likely to be exposed to contaminated soil-dwelling organisms (e.g.,
invertebrates), seeds and soil rather than the crop itself.
Minimal acute risk is expected to birds from the registered uses of cycloate. However, no
avian reproduction studies are available to assess chronic effects to birds. The acute RQs were not
calculated for birds because the toxicity data on birds indicate that the RQs will be far below any
Agency level of concern. The LC50 value for birds (>5,000 ppm) was greater than the highest dose
tested (1,440 ppm), which is the highest application rate of 4 Ibs. a.i./acre for short grass.
The Agency does not have chronic data for birds and, in the absence of this data, we cannot
preclude chronic risk to birds.
b. Risk to Small Mammals
1) Toxicity (Hazard) Assessment
Cycloate is considered practically nontoxic to small mammals on an acute oral basis.
Chronically, cycloate may affect small mammals subject to long-term exposure. The rat LD50 is
2,275 mg/kg (45,500 ppm), which is greater than the highest EEC of 960 ppm for 4 Ibs. a.i./acre on
short grass. In a 2-generation reproduction study (MRID 41691901) in the rat, cycloate was
administered to multiple generations of rats at dose levels of 50, 400 and 1,000 mg/kg/day. The
reproductive endpoint used in the cycloate mammalian wildlife risk assessment was based on
decreased pup body weight gain with a NOAEL of 50 mg/kg/day and a LOAEL of 400 mg/kg/day.
Table 11 discusses the data that support the acute and chronic toxicity endpoints used in assessing the
risks to mammals.
27
-------
Table 11. Mammalian Toxicity Endpoints for Rats Exposed to Cycloate.
Test Species
Laboratory Rat
(Rattus norvegicus)
Test Type
Mammalian
Oral
2-Generation
Reproduction
Study
Type
Acute
Chronic
%a.L
98.0
95.3
Toxicity Value
(mg/kg)
LD50 = 3,200 (a*)
LD50 = 2,275 (?)
NOAEL = 50
LOAEL = 400
Affected
Endpoints
Mortality
Reproduction
MRIDNo.
00132790
41691901
2) Exposure and Risk
Exposure to small mammals will be primarily for edge-of-field habitats, as with birds
described in the preceding section, where soil, water and food items may become contaminated by
direct application, spray drift or volatilization. Since cycloate is used before or at-planting, there are
limited food items in the field; however, the animals feeding in the field are likely to be exposed to
contaminated soil-dwelling organisms (e.g., invertebrates), seeds and soil rather than the crop itself.
The fur on the small mammals will pick up cycloate residues as they burrow in the soil, thus exposing
themselves directly to residues in the soil as they lick their fur.
Wild mammal testing is required on a case-by-case basis, depending on the results of lower tier
laboratory mammalian studies, intended use patterns and pertinent environmental fate characteristics.
Minimal acute risk to small mammals is expected from the registered uses of cycloate. Acute RQs
were not calculated for mammals because the toxicity data on rats indicate that the RQs will be far
below any Agency level of concern.
Chronic RQs range from 0.6 to 9.6 at the 2 Ibs. a.i./acre (typical) application rate. At the higher
4 Ibs. a.i./acre (maximum) application rate, the chronic RQs range from 1.2 to 19.2. Concern for
chronic risk to mammals is based on reproductive effects seen in 2- and 3-generation rat reproduction
studies. This concern extends to potential chronic effects in birds. See Table 12 for expected
environmental residues of cycloate on various food items and resulting RQs.
Table 12. Cycloate Use: Chronic RQs for Mammals.
Application Rate
(Ibs. a.L/acre)
Food Items
EEC1
(ppm)
Chronic RQ
(ppm)
Mammalian Chronic NOAEL of 2.5 mg/kg/day for Rat (2.5 / 0.05 = 50 ppm)2
2
Short grass
Broadleaf plants
Insects
Seeds
480
270
220
30
9.6
5.4
4.4
0.6
28
-------
Application Rate
(Ibs. a.L/acre)
4
Food Items
Short grass
Broadleaf plants
Insects
Seeds
EEC1
(ppm)
960
540
440
60
Chronic RQ
(ppm)
19.2
10.8
8.8
1.2
1 EEC is calculated based on the Kenaga nomogram [Hoerger and Kenaga, (1972); and as modified by Fletcher (1994)]. For
maximum concentration, the application rate in Ibs. a.i./acre is multiplied by 240 for Short Grass, 110 for Tall Grass, 135 for
broad-leafed plants/small insects and 15 for fruits/pods/large insects/seeds. Additional applications are converted from Ibs.
a.i./acre to ppm on the plant surface and the additional mass added to the mass of the chemical still present on the surface on the
day of application.
2 The rat NOAEL (in ppm) is calculated by dividing the mammalian NOAEL (in mg/kg/day) by 0.05 (to correct for actual food
consumption)
Note: Chronic RQ = EEC (ppm) / NOAEL (ppm)
c. Risk to Fish and Aquatic Invertebrates
Freshwater Species
1) Toxicity (Hazard) Assessment
The available acute toxicity data on cycloate, indicate that it is moderately toxic to freshwater
fish, based on LC50 values ranging from 4.5 ppm to 10 ppm. Cycloate is classified as slightly toxic to
freshwater invertebrates (EC50 = 24 ppm) on an acute oral basis. The LC50 value used for risk
assessment purposes is 4.5 ppm (rainbow trout). Table 13 below displays the acute toxicity endpoints
for freshwater fish and invertebrates.
Table 13. Acute Toxicity Endpoints for Freshwater Fish/Invertebrates.
Test Species
Rainbow Trout
(Oncorhynchus mykiss)
Bluegill Sunfish
(Lepomis macrochirus)
Mosquito Fish
(Gambusia affinis)
Scud
(Gammarus fasciatus)
Water Flea
(Daphnia magna)
Test Type
Fish Toxicity
Invertebrate
Toxicity
%a.L
97.8
96.8
98.6
Formulation
Technical
96.8
Toxicity Value
(ppm of a. i.)
(96-hour LC50) 4.5
(96-hour LC50) 4.6
(96-hour LC50) 6.8
(96-hour LC50) 10
(48-hour EC50) 2.6
(48-hour EC50) 24
Toxicity
Category
Moderately
Toxic
Slightly
Toxic
MRIDor
Accession No.
Ace. 090620
00143654
Ace. 072166
00084743
05001497
00143655
29
-------
Although the EEC is not expected to reach 1% or greater of any acute LC50 or EC50 value,
parent cycloate is persistent in the aquatic environment. An early life stage fish and a freshwater
invertebrate life cycle test using the TGAI (Guidelines 850.1300 and 850.1350) are required.
Without these data, the Agency cannot preclude chronic risks to aquatic organisms. The preferred
test species for the invertebrate life cycle test is Daphnia magna.
2) Exposure and Risk
Acute RQs for both federally listed endangered and threatened species and nonendangered
species of freshwater fish and aquatic invertebrates are all below Agency levels of concern. It is
predicted that the aquatic EEC will generally be less than 1% of the LC50 for fish; however, this does
not preempt the need for chronic fish or aquatic invertebrate studies if data show that terrestrial
organisms may be chronically sensitive to cycloate. It is uncertain as to whether aquatic species may
have chronic adverse impacts from cycloate use. Therefore, the early life study offish and the
aquatic invertebrate life cycle studies are required for cycloate. Table 14 below shows the RQs for
the tested species for acute exposure to freshwater fish and invertebrates.
Table 14. Acute Risk Quotients for Acute Toxicity to Freshwater Fish/Invertebrates.
Test Species
Bluegill Sunfish
(Lepomis macrochirus)
Mosquito Fish
(Gambusia qffinis)
Rainbow Trout
(Oncorhynchus mykiss)
Scud
(Gammarus fasciatus)
Water Flea
(Daphnia magna)
Study Type
(96-hour LC50)
(96-hour LC50)
(96-hour LC50)
(96-hour LC50)
(48-hour LC50)
Toxicity Endpoint Value
(ppb of a.L)
4,600
6,800
10,000
4,500
5,600
6,000
7,000
2,600
24,000
Acute RQ
0.007
0.005
0.003
0.007
0.006
0.005
0.004
0.012
0.001
Estuarine/Marine Species
Cycloate is used on spinach near estuarine areas. As indicated previously in this RED,
cycloate is expected to be persistent and moderately mobile in moist or flooded soils. As a result,
EPA will require estuarine/marine fish and invertebrate acute toxicity data (Guideline 850.1035) for
cycloate. In the absence of this data, risk assessment for estuarine/marine fish and invertebrates
cannot be completed. In addition, since parent cycloate is persistent in the aquatic environment, an
30
-------
early life stage fish test using the TGAI (Guideline 850.1300) is required for cycloate. Without these
data, the Agency cannot preclude chronic risks to aquatic organisms.
d. Risk to Nontarget Insects
Available data from a honey bee acute contact toxicity study using the TGAI indicates that
cycloate is practically nontoxic to the honeybee (with an LD50 of >29.01 jig/bee) and its uses on
garden beets, spinach and sugarbeets are predicted to pose minimal risk to nontarget insects.
e. Risk to Nontarget Terrestrial and Aquatic Plants
The degree of risk (both acute and chronic) to nontarget terrestrial and aquatic plants is
uncertain and cannot be assessed due to the complete lack of phytotoxicity data. Since cycloate is an
herbicide, EPA must presume that there is a risk to nontarget terrestrial and aquatic plants. There is
variability in phytotoxicity and specie selectivity among other thiocarbamate herbicides; therefore, it
is highly uncertain as to the degree of phytotoxicity and the selectivity of species that are sensitive to
cycloate without appropriate plant data. In the absence of these data, risk assessment to nontarget
terrestrial and aquatic plants cannot be properly completed.
Terrestrial plant testing is necessary since cycloate is an herbicide with nonresidential
terrestrial use patterns. The required terrestrial plant testing consists of seedling emergence and
vegetative vigor tests with ten crop species. Tier 1 tests (Guidelines 850.4100 and 850.4150) may be
conducted to measure the response of plants, relative to a control, at a test level that is equal to the
highest use rate (expressed as Ibs. a.i./acre) or three times the EEC for nontarget areas. Tier 2 tests
(Guidelines 850.4225 and 850.4250) are required for any test species that shows a reduction in
response equal to or greater than 25% in the Tier 1 tests.
Aquatic plant testing (Guideline 850.4400) is required for cycloate (TEP formulation)
because it is an herbicide that has outdoor nonresidential terrestrial uses. The following species
should be tested at Tier 2: Kirchneria subcapitata, Lemnagibba, Skeletonema costatum, Anabaena
flos-aquae and a freshwater diatom. In the absence of data, there is much uncertainty in the nontarget
aquatic plant risk assessment.
f. Risk to Federally Listed Endangered and Threatened Species
The Agency has developed the Endangered Species Protection Program to identify pesticides
whose use may cause adverse impacts on federally listed endangered and threatened species, and to
implement mitigation measures that address these impacts. The Endangered Species Act requires
federal agencies to ensure that their actions are not likely to jeopardize listed species or adversely
modify designated critical habitat. To analyze the potential of registered pesticide uses that may
affect any particular species, EPA uses basic toxicity and exposure data developed for the REDs and
31
-------
considers ecological parameters, pesticide use information, the geographic relationship between
specific pesticide uses and species locations and biological requirements and behavioral aspects of the
particular species. This analysis will consider the risk mitigation measures that are being
implemented as a result of this RED.
The screening level risk assessment indicates that cycloate exceeds the endangered species
level of concern for chronic risks to mammals. These findings are based solely on EPA's screening
level assessment and do not constitute "may affect" findings under the Endangered Species Act.
Cycloate has no effect on federally listed endangered and threatened fish and aquatic invertebrates
from acute and chronic exposures, and no effect on endangered and threatened birds from acute
exposure. The absence of data for birds (chronic risk) and for aquatic and terrestrial plants does not
permit EPA to preclude the potential for risks to endangered and threatened species in these areas.
The risk mitigation measures stated in this RED, such as the elimination of the chemigation
application of cycloate may potentially reduce exposure of any endangered species to this chemical.
In addition, the usage information that the Agency is requesting from the registrant may provide EPA
with sufficient data to reduce application rates in the future.
IV. Risk Management, Reregistration and Tolerance Reassessment Decision
A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of relevant
data concerning an active ingredient, whether or not products containing the active ingredient are
eligible for reregistration. The Agency has previously identified and required the submission of the
generic (i.e., active ingredient-specific) data required to support reregistration of products containing
cycloate as an active ingredient. The Agency has completed its review of these generic data and has
determined that the data are sufficient to support reregistration of all products containing cycloate.
Appendix B identifies the generic data requirements that the Agency reviewed as part of its
determination of reregistration eligibility of cycloate. These data were sufficient to allow the Agency
to determine that cycloate can be used without resulting in unreasonable adverse effects to humans
and the environment. The Agency, therefore, finds that all products containing cycloate as the active
ingredient are eligible for reregistration provided specified changes are made to the label and
additional data identified in Section V of this RED confirm this conclusion. Actions needed to
reregister particular products are addressed in Section V of this document.
The Agency may take appropriate regulatory action if new information comes to the
Agency's attention regarding the reregistration of cycloate. The Agency may also require the
submission of additional data (1) to support the registration of products containing cycloate; (2) if the
data requirements for registration change; or (3) if the guidelines for generating such data change.
32
-------
B. Regulatory Position
1. Food Quality Protection Act Findings
a. Determination of Safety for U.S. Population
The Agency has determined that the established tolerances for cycloate, with amendments
and changes as specified in this document, meet the safety standards under the FQPA amendments to
section 408(b)(2)(D) of the FFDCA, that there is a reasonable certainty of no harm for the U.S.
general population and all population subgroups. In reaching this determination, EPA considered all
available information on the toxicity, use practices and scenarios and the environmental behavior of
cycloate. Cycloate is not registered for residential (home/garden) use, nor is it used in or around
public buildings, schools or recreational areas where children or others might be exposed. Thus, there
is no expected residential or other nonoccupational exposure. Therefore, EPA considered only
dietary (food and drinking water) exposure sources in its aggregate risk assessment.
b. Aggregate Dietary Risks
The aggregate risk assessment for cycloate integrates the assessments conducted for food and
drinking water exposure only, since there are no residential uses for cycloate. For aggregate
exposure, the Agency calculates a DWLOC which represents the maximum allowable exposure
through drinking water after considering the dietary exposure to cycloate. If the EECs are less than
the DWLOCs, EPA does not have concern for aggregate exposure. No population subgroup
exceeded the Agency's level of concern for either acute or chronic dietary exposure to cycloate
based upon aggregated exposure to food plus water. Given current uses, the Agency has no risk
concerns for exposure to cycloate through food and/or water.
For cycloate, the acute dietary (food only) risk does not exceed the Agency's level of concern
for the U.S. general population and all subgroups, including infants and children, using highly
conservative assumptions. The acute dietary (food only) risk estimate is 1.1% of the aPAD at 95%
exposure, for the most highly exposed population subgroup, children aged 3-5 years. The chronic
dietary (food only) risk estimates from exposures to cycloate in food do not exceed the Agency's
level of concern (i.e., they are less than 100% of the cPAD) for the U.S. general population and all
subgroups using highly conservative assumptions. The chronic dietary (food only) risk estimate is
5.5% of the cPAD, for the most highly exposed population subgroup, children aged 3-5 years.
For cycloate, the maximum acute EECs for both surface water (52 ppb) and ground water (1
ppb) are less than the aggregate acute DWLOC calculated for the U.S. Population (2,296 ppb). The
maximum chronic EECs for both surface water (10 ppb) and ground water (1 ppb) are less than the
aggregate chronic DWLOC calculated for the U.S. general population (171 ppb), indicating that
aggregate chronic exposure to cycloate in food and water, both acute and chronic, were thus below
33
-------
the Agency's level of concern for all population subgroups for cycloate and its metabolites given
current uses.
For chronic (cancer) dietary risk assessment, the Agency has classified cycloate into the
category "not likely to be a carcinogen to humans;" therefore a quantified carcinogenic assessment is
not indicated for cycloate and no mitigation measures are necessary to address chronic (cancer)
dietary risk for cycloate.
c. Determination of Safety for Infants and Children
EPA determined that the established tolerances for cycloate meet the safety standards under
the FQPA amendments to section 408(b)(2)(C) of the FFDCA, that there is a reasonable certainty of
no harm for infants and children. The safely determination for infants and children considers the
factors noted above for the U.S. general population, but also takes into account the possibility of
increased dietary exposure due to the specific consumption patterns of infants and children, as well as
the possibility of increased susceptibility to the toxic effects of cycloate residues in this population
subgroup.
As required by the Food Quality Protection Act (1996), the hazard database for cycloate was
examined to determine the potential for increased susceptibility to infants and children from exposure
to cycloate. On August 28, 2003, the Agency's HIARC determined that no FQPA special safety
factor should be applied for special sensitivity of infants and children; and that a lOx data base
uncertainty factor (UFDB), for lack of a DNT study, should be applied to single dose (acute)
exposures, but not to multiple dose (chronic) exposures. Based upon the above, the FQPA special
safely factor has been reduced to Ix since there are no residual uncertainties for pre- and/or post-natal
toxicity.
2. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA on August 3, 1996, 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 such endocrine effects as the Administrator may designate. " Following
recommendations of its Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC),
the Agency determined that there was 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 the Agency include evaluations of potential effects in
wildlife. For pesticides, EPA will use FIFRA and, to the extent that effects in wildlife may help
determine whether a substance may have an effect in humans, FFDCA authority to require the
wildlife evaluations. As the science develops and resources allow, screening of additional hormone
systems may be added to the Endocrine Disrupter Screening Program (EDSP).
34
-------
When the appropriate screening and/or testing protocols being considered under the Agency's
EDSP have been developed, cycloate may be subject to additional screening and/or testing to better
characterize effects related to endocrine disruption.
3. Cumulative Risks
Section 408(b)(2)(D)(v) of the FFDCA 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." The reason for consideration of other substances is due to the possibility that low-level
exposures to multiple chemical substances that cause a common toxic effect by a common
mechanism could lead to the same adverse health effect as would a high level of exposure to any one
of the other substances individually. OPP has determined that some thiocarbamates (EPIC, molinate,
pebulate and cycloate) share a common mechanism of toxicity, the inhibition of acetylcholinesterase.
In September 2001, the Scientific Advisory Panel (SAP) concluded that there is insufficient evidence
for grouping the thiocarbamate pesticides based on a common mechanism of toxicity for effects other
than acetylcholinesterase inhibition. Although structural and metabolic similarities exist among the
thiocarbamates and there is evidence that the thiocarbamates may produce a common effect
(neuropathology), this evidence is not definitive. The Agency has conducted a preliminary
"screening level" cumulative food risk assessment for the thiocarbamates. The results of the
screening level cumulative food risk assessment, using very conservative Tier 1 exposure
assumptions (using tolerance level residues, assuming 100% of all crops treated and including
exposures from molinate, which is being phased out), is that MOEs exceed 310 for all population
subgroups. Since any MOE greater than 100 is deemed acceptable, the Agency has concluded that
the potential cumulative risks from the thiocarbamates in general and cycloate in particular passes the
"reasonable certainty of no harm" standard of the Food Quality Protection Act.
These results are reported in a memorandum dated December 19, 2001 from Marcia Mulkey
entitled, "Thiocarbamates: A Determination of the Existence of a Common Mechanism of Toxicity
and a Screening Level Cumulative Food Risk Assessment." This document can be found under
thiocarbamates at the EPA website entitled, "Public Comment Period Opened: Common Mechanism
Determination for Thiocarbamate and Dithiocarbamate Pesticides" at
http://www.epa. sov/oppsrrdl/cumulative/thiocar. htm.
C. Tolerance Reassessment Summary
The existing tolerances for residues of cycloate in/on plant commodities are established under
40 CFR §180.212. These tolerances are presently expressed in terms of cycloate (S-ethyl
cyclohexyl(ethyl)thiocarbamate),/>er se. No cycloate tolerances for livestock commodities or
processed food/feed commodities are currently established. The Agency has determined that the total
toxic residues to be regulated in the target crops should consist of cycloate and the free and
35
-------
conjugated forms of its metabolites (3HC and 4HC). The Agency is now recommending that the
tolerance expression should be amended to reflect this determination.
The Agency has also determined that tolerances for milk, meat and meat byproducts of
livestock are not required (Category 3, 40 CFR §180.6) for reregistration. There are no poultry
feedstuffs associated with the registered food/feed uses; therefore, cycloate tolerances are not required
for eggs and the meat and meat byproducts of poultry. A summary of cycloate tolerance
reassessments is presented below in Table 15.
1. Tolerances Currently Listed Under 40 CFR §180.212
Adequate residue data are available to ascertain the adequacy of tolerances for Beet, garden,
roots; Beet, garden, tops; and Spinach. For these commodities, the established tolerance levels have
been increased to accommodate inclusion of the cycloate metabolites.
Adequate residue data are also available to support the registered Section 3 uses on Beet,
sugar, roots and Beet, sugar, tops; however, inadequate data are available to support a Section 24(c)
(CA780075) registration for use on sugarbeets, which specifies a higher rate of 6 Ibs. a.i./acre. The
reassessed tolerances for Beet, sugar, roots and Beet, sugar, tops assumes that the above Section 24(c)
product will be canceled.
The group commodity definition "Garden beets (roots and tops)" should be revised to "Beet,
garden, roots" and "Beet, garden, tops." The group commodity definition "Sugarbeets (roots and
tops)" should be revised to "Beet, sugar, roots" and "Beet, sugar, tops."
2. Tolerance to Be Proposed Under 40 CFR §180.212
The registrant must propose a tolerance for Beet, sugar, molasses. The available data suggest
that a tolerance level of 1.0 ppm is appropriate. The registrant must also propose a tolerance for
Swiss chard. The Agency recommends 5.0 ppm.
Table 15. Tolerance Reassessment Summary for Cycloate.
Commodity
Current Tolerance1
(ppm)
Reassessed Tolerance2
(ppm)
Comment
[Corrected Commodity Definition]
Tolerances Currently Listed Under 40 CFR §180.212
Garden beets
(roots and tops)
Spinach
Sugarbeets
(roots and tops)
0.05
0.05
0.05
Roots: 0.50
Tops: 1.0
0.5
Roots: 0.3
Tops: 0.3
[Beet, garden, roots]
[Beet, garden, tops]
[Beet, sugar, roots]
[Beet, sugar, tops]
36
-------
Commodity
Current Tolerance1
(ppm)
Reassessed Tolerance2
(ppm)
Comment
[Corrected Commodity Definition]
Tolerances To Be Proposed Under 40 CFR §180.212
Beets, sugar, molasses
Swiss chard
None
N/A
1.0
5.0
1 Expressed in terms of cy cloate, perse.
2 To be expressed in terms of cy cloate and the free and conjugated forms of 3HC and 4HC. Reassessment is also contingent
upon label revisions to specify minimum pre-harvest intervals of 60 days for garden beets, 120 days for sugarbeets and 60
days for spinach.
4. Codex Harmonization
No Codex maximum residue levels (MRLs) have been established for cycloate and its
metabolites; therefore, issues of compatibility between Codex MRLs and U.S. tolerances do not exist.
5. Residue Analytical Methods
Adequate residue analytical methods are available for tolerance enforcement and data
collection. No additional data pertaining to this guideline topic are required for reregistration. The
available methods for determining cycloate residues of concern in/on plant commodities is described
below.
Plants:
An analytical method based upon the steam distillation of cycloate from plants and
measurement by GC using FID is currently listed in PAMII as Method A for determination of S-
ethyl cyclohexyl(ethyl)thiocarbamate. The method was determined to be adequate for enforcement
and collection of data on cycloate,per se, in/on plant commodities. (List B. Residue Analytical
Methods Inventory, R. Perfetti, June 22, 1990). However, the Agency determined in 1992 that a new
enforcement method was needed that would be capable of determining not only cycloate, but also its
3HC and 4HC metabolites in/on plants (CBRS No. 9028, DP Barcode D171952, C. Olinger, May 19,
1992). The analytical method(s) also was required to include a hydrolysis step to release any
conjugated residues of 3HC or 4HC.
To meet this requirement, the registrant submitted a GC/NPD residue analytical method in
1995 (MRID 43523801), that can determine 3HC and 4HC, as well as cycloate, and includes the
requisite hydrolysis step to release bound residues of 3HC and 4HC. The reported limit of
quantification (LOQ) for each metabolite was 0.05 ppm. Residue identification can be confirmed by
GC/MS. Although submitted validation data were acceptable for data collection and for tolerance
enforcement, the recoveries tended to run too high (>120%) and also to have standard deviations that
sometimes exceeded 20%. The submitted data did not support tolerance enforcement on spinach.
37
-------
This method was subjected to an independent laboratory evaluation (ILV) on garden beet
roots and tops, in accordance with PR Notice 96-1. This ILV incorporated certain modifications to
improve performance. With these modifications, the ILV adequately supported use of this method on
garden beet tops and also roots, but did not address spinach. Subsequent to this ILV, a field trial was
submitted for Swiss chard. In this field trial, this same method was performed on Swiss chard by an
IR-4 laboratory. The IR-4 laboratory had excellent recoveries and repeatabilities for all 5 analytes in
Swiss chard, even at 0.05 ppm. After a review of this data, EPA concluded that the information from
this field trial can be used as equivalent to an additional ILV and that, based upon performance of the
method in this field trial, this method can be construed by weight-of-the-evidence to be adequate for
enforcement of cycloate residues in/on all registered commodities, including spinach.
The requirement for radiovalidation of the new method has not yet been fulfilled. A
radiovalidation study of this method must be submitted.
Animals:
No method is required for residues in livestock.
D. Regulatory Rationale
The regulatory rationale for each of the mitigation measures outlined below is discussed
immediately after this list of mitigation measures. These mitigation measures will reduce risks to
agricultural workers:
• Voluntary cancellation of chemigation application of cycloate;
• Extend the cycloate REI to 48-hours;
• Require engineering controls including closed cabs and closed mixing/loading systems;
• Prohibit on-farm impregnation of cycloate onto dry bulk fertilizer; and
• Require use data to better characterize exposure from dry bulk fertilizer applications.
The following is a summary of the rationale for the measures specified above which are
necessary for reregistration eligibility and for managing risks associated with the use of cycloate.
Where labeling revisions are warranted, specific language is set forth in the summary table of Section
V (Table 16 of this RED document).
38
-------
1. Human Health Risk Mitigation
a. Dietary Mitigation
(1) Acute Dietary (Food)
Acute dietary (food only) risk does not exceed the Agency's level of concern for the U.S.
general population and all population subgroups, including infants and children, using highly
conservative assumptions. The acute dietary (food only) risk estimate is 1.1% of the aPAD at 95%
exposure, for the most highly exposed population subgroup, children aged 3-5 years. No mitigation is
necessary for acute dietary (food only) exposure.
(2) Chronic Dietary (Food)
The chronic dietary (food only) risk estimates from exposures to cycloate in food do not
exceed the Agency's level of concern (i.e., they are less than 100% of the cPAD) for the U.S. general
population and all population subgroups using highly conservative assumptions. The chronic dietary
(food only) risk estimate is 5.5% of the cPAD, for the most highly exposed population subgroup,
children aged 3-5 years. No mitigation is necessary for chronic dietary (food only) exposure.
(3) Drinking Water
Estimated environmental concentrations of cycloate and its metabolites for both surface and
ground water sources of drinking water are below the Agency's DWLOCs, indicating that aggregate
chronic exposure to cycloate in food and water, both acute and chronic, were thus below the
Agency's level of concern for all population subgroups. No mitigation is needed for drinking water.
(4) Residential
The Agency is not considering residential mitigation options for cycloate since there are no
existing or proposed residential or other nonoccupational sources of exposure and cycloate is not used
in or around public buildings, schools or recreational areas where children or others might be
exposed.
(5) Aggregate
Since there are no residential uses for cycloate, the aggregate risk assessment considered the
combined risk from exposure through food and drinking water only. In general, combined risks from
these exposures are less than 100% of the cPAD and are not considered to be a risk concern. No
39
-------
population subgroup exceeded the Agency's level of concern for either acute or chronic dietary
exposure to cycloate based upon aggregated exposure to food plus water. Given current uses, the
Agency has no risk concerns for exposure to cycloate through food and/or water. No mitigation is
necessary for aggregate exposure.
b. Occupational Risk Mitigation
(1) Handler Exposure
There is a potential risk for short- and intermediate-term dermal and inhalation exposures in
occupational settings from mixing, loading and applying cycloate products. For the garden beet,
spinach and sugarbeet uses, potential risks for the following occupational exposure scenarios can be
addressed with engineering controls:
• Scenario (2) closed system mixing/loading of EC liquid formulation for groundboom applications
to garden beets, spinach and sugarbeets (dermal exposure only);
• Scenario (4) applying liquid sprays by groundboom equipment with an enclosed cab to garden
beets, spinach and sugarbeets (dermal and inhalation exposure); and
• Scenario (5) applying impregnated dry bulk fertilizers with tractor drawn spreader with an
enclosed cab to sugarbeets (dermal exposure only).
Even taking into account maximum PPE and engineering controls, three (3) occupational
exposure scenarios do not achieve the target MOE of 300 for inhalation exposure. In these instances,
EPA first characterizes the handler risk estimates (high acreage/application rates) by examining the
assumptions used in the risk assessment, the strengths and weaknesses of existing data and the
potential for additional data to further refine the risk assessments. The Agency then considers the
benefits of a pesticide's use, in making its risk management decision.
The following is a detailed consideration for the scenario where current estimates show
MOEs of less than the specified target MOE of 100 for dermal exposure:
Scenario (1) closed system mixing/loading of EC liquid formulation for chemigation application to
garden beets, spinach and sugarbeets at 350 acres per day at 4 Ibs. a.i./acre
A current dermal MOE estimate of 58 was assessed, assuming maximum acreage at
maximum application rate. Even with closed mixing/loading, the dermal risk estimate still exceeds
the Agency's LOG (MOEs <100) for EC liquid formulation for chemigation application to garden
beets, spinach and sugarbeets To address this handler concern, the Agency has proposed and the
registrant has agreed to voluntarily cancel the chemigation application of cycloate.
40
-------
The following are detailed considerations for each scenario where current estimates show
MOEs of less than the specified target MOE of 300 for inhalation exposure:
Scenario (1) closed system mixing/loading of liquid formulation for chemigation application to
garden beets, spinach and sugarbeets at 350 acres at per day 4 Ibs. a.i./acre
A current inhalation MOE estimate of 150 was assessed, assuming maximum acreage at
maximum application rate. Even with closed mixing/loading, the inhalation risk estimate still
exceeds the Agency's LOG (MOEs <300) for EC liquid formulation for chemigation application to
garden beets, spinach and sugarbeets To address this handler concern, the Agency has proposed
and the registrant has agreed to voluntarily cancel the chemigation application of cycloate.
Scenario (2) closed system mixing/loading of liquid formulation for groundboom applications to
garden beets and sugarbeets at 200 acres per day at 4 Ibs. a.i./acre
The risk assessment for this scenario was conducted at the maximum application rate and at
80 and 200 acres treated daily. At 80 acres treated, the inhalation MOE is 660. At 200 acres treated,
the inhalation MOE is 260. Information received from garden beet and sugarbeet growers indicates
that, typically, less than 200 acres are actually treated with cycloate in a day. Comments from
sugarbeet growers also indicate that less than the maximum application rate of 4 Ibs. a.i./acre is used.
Therefore, the Agency believes that the amount of cycloate handled in a day is actually less than the
maximum value assessed by the Agency. Use and usage information on the typical application
rate and maximum daily acres treated for this scenario will be required.
Scenario (3) closed system mixing/loading and impregnation of EC liquid formulation onto dry bulk
fertilizers to sugarbeets at 200 acres per day at 4 Ibs. a.i./acre: and
Scenario (5) applying impregnated dry bulk fertilizers with enclosed cabs to sugarbeets at 80 and 200
acres per day at 4 Ibs. a.i./acre
The risk assessment for Scenario (3) was conducted at the maximum application rate and at
80 and 200 acres treated daily. At 80 acres treated per day, the MOE is 320. At 200 acres treated per
day, the MOE is 130. For Scenario (5), current MOE estimates ranging from 250 at 80 acres treated
per day to 99 for 200 acres treated per day, assuming maximum acreage at maximum application rate.
Information received from sugarbeet growers indicates that, typically, less than the maximum
application rate of 4 Ibs. a.i./acre is used during the impregnation process and, in many cases, may be
at half the maximum application rate. Therefore, the Agency believes that the amount of cycloate
handled in a day is actually less than the maximum value assessed by the Agency. Use and usage
information on the typical application rate and maximum daily acres treated for this scenario
will be required.
Comments from the sugarbeet growers also indicate that the on-farm impregnation of
cycloate onto dry bulk fertilizer does not occur. The impregnation work is being conducted in
commercial settings utilizing an enclosed mixing/loading system. As such, the Agency has
41
-------
proposed and the registrant has agreed to prohibit on-farm impregnation of cycloate onto dry
bulk fertilizer. Therefore, the impregnation of cycloate onto dry bulk fertilizer will be restricted
to commercial settings only.
(2) Post-Application Exposure
Since cycloate is incorporated into the soil either immediately or within a few hours after
application, post-application exposures are expected to be negligible. As a result, post-application
scenarios were not assessed. Due to the volatility of cycloate, the REI will be extended from the
current 12 hours to 48 hours. However, workers will be allowed to enter the treated area during
the first 48 hours following application to plant crops, provided they follow the early reentry
language on the label.
2. Environmental Risk Mitigation
a. Birds
Minimal acute risk is expected to birds from the registered uses of cycloate. However, no
avian reproduction studies are available to assess chronic effects to birds. The acute RQs were not
calculated for birds because the toxicity data on birds indicate that the RQs will be far below any
Agency level of concern. The LC50 value for birds (>5,000 ppm) was greater than the highest dose
tested (1,440 ppm), which is the highest application rate of 4 Ibs. a.i./acre for short grass.
Currently, EPA does not have chronic toxicity data for birds and in the absence of this data,
we cannot preclude chronic risks to birds, as discussed in Section V. A. 1 of this document. The
Agency reserves the right to impose environmental risk mitigation strategies for cycloate, once the
avian chronic toxicity data has been reviewed.
b. Mammals
Minimal acute risk to small mammals is expected from the registered uses of cycloate. Acute
RQs were not calculated for small mammals because the toxicity data on rats indicate that the RQs
will be far below any Agency level of concern. Chronic RQs range from 0.6 to 9.6 at the 2 Ibs.
a.i./acre (typical) application rate. At the higher 4 Ibs. a.i./acre (maximum) application rate, the
chronic RQs range from 1.2 to 19.2. The chronic risk to small mammals will be primarily for edge-
of-field habitats, as with birds described in the preceding section, where soil, water and food items
may become contaminated by direct application, spray drift or volatilization. Since cycloate is used
before or at-planting, there are limited food items in the field; however, the animals feeding in the
field are more likely to be exposed to contaminated spoil-dwelling organisms (e.g., invertebrates),
seeds and soil rather than the crop itself. The fur on the small mammals will pick up cycloate
42
-------
residues as they burrow in the soil, thus exposing themselves directly to residues in the soil as they
lick their fur.
c. Fish and Aquatic Invertebrates
Freshwater Species
Cycloate is moderately toxic to freshwater fish (based on LC50 values ranging from 4.5 ppm to
10 ppm) and slightly toxic to freshwater invertebrates (EC50 = 24 ppm). Acute RQs for both federally
listed endangered and threatened species and nonendangered species of freshwater fish and aquatic
invertebrates are all below Agency levels of concern.
Although the EEC is not expected to reach 1% or greater of any acute LC50 or EC50 value,
parent cycloate is persistent in the aquatic environment. This does not preempt the need for chronic
fish or aquatic invertebrate studies if data show that terrestrial organisms may be chronically sensitive
to cycloate. It is uncertain as to whether aquatic species may have chronic adverse impacts from
cycloate use. Since parent cycloate is persistent in the aquatic environment, an early life stage fish
and a freshwater invertebrate life cycle test using the TGAI (Guidelines 850.1300 and 850.1350) are
required. Without these data, the Agency cannot preclude chronic risks to aquatic organisms. The
preferred test species for the invertebrate life cycle test is Daphnia magna.
Estuarine/Marine Species
Cycloate is used on spinach near estuarine areas and is expected to be persistent and
moderately mobile in moist or flooded soils. As a result, EPA requires an estuarine/marine fish and
invertebrate acute toxicity data (Guideline 850.1035) for cycloate. In the absence of this data, risk
assessment for estuarine/marine fish and invertebrates cannot be completed.
d. Nontarget Insects
Available data indicate that technical cycloate is practically nontoxic to the honeybee. The
labeled uses for cycloate on garden beets, spinach and sugarbeets are predicted to not exceed any
LOG for risk to nontarget insects. No mitigation is necessary for nontarget insects.
e. Nontarget Terrestrial and Aquatic Plants
Exposure is expected to nontarget plants from runoff, volatility and spray drift (from Center-
Pivot, Lateral Move, End Tow and Traveler irrigation systems). The degree of risk (both acute and
chronic) to nontarget terrestrial and aquatic plants is uncertain and cannot be assessed by EPA due to
the complete lack of phytotoxicity data. Since cycloate is an herbicide, EPA must presume that there
43
-------
is a risk to nontarget terrestrial and aquatic plants. Terrestrial plant testing is necessary since cycloate
is an herbicide with nonresidential terrestrial use patterns. The required Tier 1 terrestrial plant testing
on cycloate (TEP formulation) consisting of seedling emergence and vegetative vigor tests with ten
crop species (Guidelines 850.4100 and 850.4150). Tier 2 tests (Guidelines 850.4225 and 850.4250)
will be required for any test species that shows a reduction in response equal to or greater than 25% in
the Tier 1 tests. Therefore, Tier 2 tests are held in reserve, pending the outcome of the Tier 1 tests.
A Tier 2 aquatic plant growth test (Guideline 850.4400) is required for cycloate TEP because
it is an herbicide that has outdoor nonresidential terrestrial uses. The following species should be
tested at Tier 2: Kirchneria subcapitata, Lemna gibba, Skeletonema costatum, Anabaena flos-aquae
and a freshwater diatom. Without the above data, the Agency must preclude acute and chronic risk to
nontarget terrestrial and aquatic plants.
f. Summary of Environmental Risk Mitigation
The EFED risk assessment for cycloate is limited because of lack of data to assess chronic
risk to birds and risk to plants. Therefore, avian reproduction data, seedling emergence, vegetative
vigor and aquatic plant growth; and acute toxicity data for estuarine/marine animals are required. The
registrant has agreed to submit data on cycloate, that will allow the Agency to adequately assess the
ecological effects of cycloate, thus refining these risk estimates. The Agency reserves the right to
impose environmental risk mitigation strategies for cycloate, once these data have been reviewed.
The following label statement is needed to address ecological concerns for cycloate:
Surface Water Label Advisory
"Do not apply directly to water, to areas where surface water is present or to intertidal areas
below the mean high water mark. Do not apply when weather conditions favor drift from the target
area. Do not contaminate water when disposing of equipment wash water."
E. Other Labeling Requirements
Other use and safety information needed for labeling of all end-use products containing
cycloate are indicated in Table 16.
1. Endangered Species
The Agency has developed the Endangered Species Protection Program to identify pesticides
whose use may cause adverse impacts on federally listed endangered and threatened species, and to
implement mitigation measures that address these impacts. The Endangered Species Act requires
federal agencies to ensure that their actions are not likely to jeopardize listed species or adversely
44
-------
modify designated critical habitat. To analyze the potential of registered pesticide uses that may
affect any particular species, EPA uses basic toxicity and exposure data developed for the REDs and
considers ecological parameters, pesticide use information, the geographic relationship between
specific pesticide uses and species locations and biological requirements and behavioral aspects of the
particular species. This analysis will consider the risk mitigation measures that are being
implemented as a result of this RED.
A determination that there is a likelihood of potential impact to a listed species may result in
limitations on use of the pesticide, other measures to mitigate any potential impact or consultations
with the Fish and Wildlife Service and/or the National Marine Fisheries Service as necessary.
The Endangered Species Protection Program as described in a. Federal Register notice (54 FR
27984-28008, July 3, 1989) is currently being implemented on an interim basis. As part of the
interim program, the Agency has developed County Specific Bulletins that articulate many of the
specific measures outlined in the Biological Opinions issued to date. The Bulletins are available for
voluntary use by pesticide applicators on EPA's website at http://www.epa.gov/espp.
2. Spray Drift Management
Cycloate must be incorporated into the soil immediately after application, to be effective and
to avoid substantial losses due to volatilization. The methods used to apply and incorporate cycloate
into the soil affect the rate of volatilization. During chemigation, cycloate volatilizes at a higher rate
than with mechanical incorporation methods, increasing the potential for off-site drift. The
chemigation application of cycloate has been voluntarily cancelled by the registrants. Since all
remaining application methods involve mechanical incorporation into the soil, EPA anticipates low
potential for off-site drift.
3. For Commercial Use Only
There are no existing or proposed uses of cycloate for residential (home/garden) use, nor is it
used in or around public buildings, schools or other recreational areas where children might be
exposed. Cycloate is currently registered for use in commercial settings only. Non-commercial use
is prohibited. All product labels will be amended to state that cycloate is "For commercial use only."
45
-------
V. Actions Required of Registrants
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregistration of cycloate for the eligible uses has been
reviewed and determined to be substantially complete. The following confirmatory data requirements
have been identified by the Agency:
Guideline Test Name
Stability on TGAI
Ultraviolet/Visible Absorption
Solubility
Field Accumulation in Rotational Crops
Terrestrial Field Dissipation Study #2
Estuarine/Marine Fish Acute Toxicity on TGAI
Estuarine/Marine Invertebrate Acute Toxicity on TGAI
Fish-Early Life Stage on TGAI
Invertebrate Life Cycle Test on TGAI
Avian Reproduction - Bobwhite Quail on TGAI
Avian Reproduction - Mallard Duck on TGAI
Seedling Germination/Seedling Emergence, Tier 1 (10 most sensitive species from
testing with parent compound) on TEP
Vegetative Vigor, Tier 1(10 most sensitive species from testing with parent
compound) on TEP
Aquatic Plant Growth, Tier 2 (5 most sensitive species) on TEP
Multiresidue Methods (3- and 4-hydroxy cycloate metabolites)
Developmental Neurotoxicity Study, Rat
New OPPTS
Guideline No.
830.6313
830.7050
830.7840
835.1900
835.6100
850.1035
850.1300
850.1350
850.2300
850.4100
850.4150
850.4400
860.1360
870.6300
Old Guideline
No.
63-13
None
63-8
165-2
164-1
72-3A
72-3C
72-4A
72-4B
71-4A
71-4B
122-1A
122-1B
123-2
171-4M
83-6
46
-------
a. Product Chemistry Data
Acceptable data pertaining to thermal stability data have been submitted; however, data are
required concerning the stability of the TGAI (Guideline 830.6313) upon exposure to metals and
metal ions.
According to OPPTS Series 830, Product Properties Test Guidelines, the Agency requires
data pertaining to ultraviolet/visible absorption (Guideline 830.7050) for the PAL
Acceptable data pertaining to solubility in water have been submitted; however, data are
required demonstrating the solubility of the TGAI in representative polar and nonpolar solvents at 20°
or 25° C.
b. Environmental Fate Data
Limited field rotational crop trials (Guideline 835.1900) are required because cycloate
residues of concern were detected in/on samples of rotational crop commodities from the reviewed
field rotational crop study. The need for rotational crop tolerances and restrictions will be determined
following submission of the required field rotational crop studies.
EPA generally requires two acceptable terrestrial field dissipation (TFD) studies (Guideline
835.6100). There is currently one acceptable TFD study from California; however, the Agency
requires a second TFD be performed. A site in the Red River Valley of the North is preferable, and a
module to measure volatilization as well as dissipation from the soil is requested. Based on
uncertainties identified in the drinking water assessment, a monitoring study for cycloate sulfoxide
should be incorporated into the TFD study.
There are outstanding data needs for the primary degradate, cycloate sulfoxide. Cycloate
sulfoxide, is considered to be potentially bio-active according to OPP's Health Effects Division
("Results of October 31, 2000 MARC Committee Meeting on Molinate Degradates in Water," memo
dated November 30, 2000; DP Barcode D270853). There are currently no fate and transport data
available on the sulfoxide degradate of cycloate. In order to ascertain toxicity to the environment, a
soil photodegradation study on cycloate sulfoxide (Guideline 835.2410) is held in reserve, pending
the review of data submitted on parent cycloate.
47
-------
c. Ecological Effects Data
Since cycloate is used on spinach near estuarine areas, EPA will require estuarine/marine fish
and invertebrate acute toxicity data (Guidelines 850.1035) for the cycloate TGAI. In the absence of
this data, risk assessment for estuarine/marine fish and invertebrates cannot be completed. In
addition, since parent cycloate is persistent in the aquatic environment, an early life stage fish and a
freshwater invertebrate life cycle test using the TGAI (Guidelines 850.1300 and 850.1350) are
required. The preferred test species for the invertebrate life cycle test is Daphnia magna. Without
these data, the Agency cannot preclude chronic risks to aquatic organisms.
Avian reproductive studies (Guideline 850.2300) using the TGAI are required for cycloate
because the pesticide is stable in the environment to the extent that potentially toxic amounts may
persist in animal feed, especially preceding or during the breeding season and information derived
from mammalian reproduction studies indicates reproduction in terrestrial vertebrates may be
adversely affected by the anticipated use of the product. In the absence of data, potential chronic risk
to birds must be presumed. The value of having the avian reproduction study done is very high.
Terrestrial plant testing is necessary since cycloate is an herbicide with nonresidential
terrestrial use patterns. Tier 1 terrestrial plant testing is required on cycloate (TEP formulation),
consisting of seedling emergence and vegetative vigor tests with ten crop species (Guidelines
850.4100 and 850.4150). Tier 2 tests (Guidelines 850.4225 and 850.4250) will be required for any
test species that shows a reduction in response equal to or greater than 25% in the Tier 1 tests.
Therefore, Tier 2 tests are held in reserve, pending the outcome of the Tier 1 tests.
Aquatic plant growth testing (Guideline 850.4400) is required for the cycloate TEP because it
is an herbicide that has outdoor nonresidential terrestrial uses. The following species should be tested
at Tier 2: Kirchneria subcapitata, Lemnagibba, Skeletonema costatum, Anabaenaflos-aquae and a
freshwater diatom. Without the above data, the Agency must preclude acute and chronic risk to
nontarget terrestrial and aquatic plants.
As mentioned in the ecological effects section, there are outstanding data needs for cycloate
sulfoxide. There is uncertainty regarding potential risk to aquatic and terrestrial organisms from
cycloate sulfoxide. In order to ascertain toxicity to the environment, an avian subacute dietary
toxicity test on cycloate sulfoxide (Guideline 850.2200) is held in reserve, pending the review of
submitted data on parent cycloate.
d. Residue Chemistry Data
The registrant has submitted a new residue analytical method (GC/NPD) for cycloate and its
plant metabolites which need to be included in the tolerance expression. The new GC/NPD method,
must be radiovalidated.
48
-------
The reregistration requirements for multiresidue methods data are not yet fulfilled.
Multiresidue methods data (Guideline 860.1360) are required to provide recovery data through the
PAMI protocol for cycloate's 3HC and 4HC metabolites. The registrant should follow the directions
for the protocols found in PAM Volume I, Appendix II, starting with the decision tree for
multiresidue methods testing (i.e., decisions on what protocols to follow and proper applications of
the methods).
e. Toxicological Data
There is concern for developmental neurotoxicity resulting from exposure to cycloate. A
developmental neurotoxicity study (including cholinesterase measures) in the rat has been identified
as a data gap.
2. Labeling for Manufacturing-Use Products
To remain in compliance with FIFRA, manufacturing-use product (MUP) labeling should be
revised to comply with all current EPA regulations, PR Notices and applicable policies. The MUP
labeling should bear the labeling contained in the table at the end of this section. The MUP label will
explicitly prohibit use of products that do not conform to Section V.B.2 of this document.
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific data
regarding the pesticide after a determination of eligibility has been made. Registrants must review
previous data submissions to ensure that they meet current EPA acceptance criteria and if not, commit
to conduct new studies. If a registrant believes that previously submitted data meet current testing
standards, then the study MRID numbers should be cited according to the instructions in the
Requirement Status and Registrants Response Form provided for each product.
2. Labeling for End-Use Products
Labeling changes are necessary to implement measures outlined in Section V above. Specific
language to implement these changes is specified in Table 16 at the end of this section.
49
-------
C. Labeling Changes Summary Table
In order to be eligible for reregistration, amend all product labels to incorporate the risk
mitigation measures outlined in Section IV. The following table (Table 16) describes how language
on the labels should be amended.
50
-------
Table 16. Summary of Required Labeling Changes for Cycloate
Description
Amended Labeling Language
Placement on Label
Manufacturing Use Products
For all Manufacturing Use
Products
"Only for formulation into an herbicide for the following use(s) [fill blank only with those uses that are
being supported by MP registrant]."
Directions for Use
One of these statements may be
added to a label to allow
reformulation of the product for a
specific use or all additional uses
supported by a formulator or user
group
"This product may be used to formulate products for specific use(s) not listed on the MP label if the
formulator, user group, or grower has complied with U. S. EPA submission requirements regarding
support of such use(s)."
"This product may be used to formulate products for any additional use(s) not listed on the MP label if the
formulator, user group, or grower has complied with U. S. EPA submission requirements regarding
support of such use(s)."
Directions for Use
Environmental Hazards
Statements Required by the RED
and Agency Label Policies
"Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or other
waters unless in accordance with the requirements of a National Pollution Discharge Elimination System
(NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not
discharge effluent containing this product to sewer systems without previously notifying the local sewage
treatment plant authority. For guidance, contact your State Water Board or Regional Office of the EPA."
Precautionary Statements
End-Use Products Intended for Occupational Use (WPS)
PPE Requirements Established by
the RED1 for Liquid Formulations
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are" (registrant inserts correct chemical-
resistant material). "If you want more options, follow the instructions for category" [registrant inserts
A,B, C,D,E,F, G, or H] "on an EPA chemical-resistance category selection chart."
"Engineering controls are required for all mixers, loaders and applicators (see Engineering Controls for
additional requirements)."
"All mixers, loaders, applicators, and other handlers must wear at a minumum:
- Long-sleeved shirt and long pants,
- Shoes plus socks, and
- Chemical-resistant gloves and chemical-resistant apron when mixing and loading."
Immediately following/below
Precautionary Statements: Hazards to
Humans and Domestic Animals
51
-------
Description
Amended Labeling Language
Placement on Label
PPE Requirements Established by
the RED1 for Liquid Formulations,
continued
"Handlers performing tasks, such as spill clean-up or cleaning equipment, for which engineering controls
are not feasible must wear:
- Long-sleeved shirt and long pants,
- Shoes plus socks,
- Chemical-resistant gloves,
- Chemical-resistant apron, and
- A NIOSH-approved respirator with
- an organic-vapor removing cartridge with a prefilter approved for pesticides (MSHA/NIOSH
approval number prefix TC-23C), or
- a canister approved for pesticides (MSHA/NIOSH approval number prefix TC-14G), or
- an organic-vapor cartridge or canister with any N2, R or P or He prefilter."
Immediately following/below
Precautionary Statements: Hazards to
Humans and Domestic Animals
User Safety Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for washables
exist, use detergent and hot water. Keep and wash PPE separately from other laundry."
"Discard clothing and other absorbent materials that have been drenched or heavily contaminated with this
product's concentrate. Do not reuse them."
Precautionary Statements: Hazards to
Humans and Domestic Animals
(Immediately following the PPE
requirements)
Engineering Controls: Liquid
Formulations
"Engineering Controls"
"Mixers and loaders must use a closed system that meets the requirements listed in the Worker
Protection Standard (WPS) for agricultural pesticides [40 CFR 170.240(d)(4)] for dermal protection, and
must:
- Wear the personal protective equipment required in the PPE section of this labeling for mixers and
loaders,
- Wear protective eyewear, if the system operates under pressure,
- Either use a closed system that also meets the requirements in the WPS for inhalation protection or wear
the type of respirator specified in the personal protective equipment sections of the labeling, and
- Be provided and have immediately available for use in an emergency, such as a spill or equipment
breakdown: chemical-resistant footwear, and, if using a closed system cab that provides respiratory
protection, a respirator of the type specified in the PPE section of this labeling."
Precautionary Statements: Hazards to
Humans and Domestic Animals
(Immediately following PPE and User
Safety Requirements)
52
-------
Description
Amended Labeling Language
Placement on Label
Engineering Controls: Liquid
Formulations, continued
"Applicators must use motorized ground equipment that is equipped with an enclosed cab that meets the
definition in the Worker Protection Standard for Agricultural Pesticides [40 CFR 170.240(d)(5)] for
dermal protection. In addition, applicators must:
- Wear the personal protective equipment required in the PPE section of this labeling for applicators,
- Either wear the type of respirator specified in the PPE section of this labeling or use an enclosed cab
with a properly functioning ventilation system that is used and maintained according to the
manufacturer's written operating instructions and that is declared in writing by the manufacturer or by a
government agency to provide at least as much respiratory protection as the type of respirator specified in
the PPE section of this labeling,
- Be provided and have immediately available for use in an emergency for when they must exit the cab in
the treated area: chemical-resistant gloves, and, if using an enclosed cab that provides respiratory
protection, a respirator of the type specified in the PPE section of this labeling,
- Take off any PPE that was worn in the treated area before reentering the cab, and
- Store all such PPE in a chemical-resistant container, such as a plastic bag, to prevent contamination of
the inside of the cab."
Precautionary Statements: Hazards to
Humans and Domestic Animals
(Immediately following PPE and User
Safety Requirements)
Additional Mitigation Measures
for Handlers and Applicators in
California
Remove all of the language from the current label under the heading "Additional Mitigation Measures for
Handlers and Applicators in California."
Add the following section:
"Additional Use Limitations for California Only: Mixers, loaders, applicators, and other handlers are
prohibited from handling more than 93 gallons (560 pounds active ingredient) in any 21-day period.
Property operators must include in their Pesticide Use Records the name of the person(s) who handled the
product for each application"
Precautionary Statements: Hazards to
Humans and Domestic Animals
(Immediately following the PPE
requirements)
User Safety Recommendations
"User Safety Recommendations"
"Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the toilet.
Users should remove clothing/PPE immediately if pesticide gets inside. Then wash thoroughly and put on
clean clothing.
Users should remove PPE immediately after handling this product. Wash the outside of gloves before
removing. As soon as possible, wash thoroughly and change into clean clothing."
Precautionary Statements under:
Hazards to Humans and Domestic
Animals immediately following
Engineering Controls
(Must be placed in a box)
Environmental Hazards
"Do not apply directly to water, to areas where surface water is present or to intertidal areas below the
mean high water mark. Do not apply when weather conditions favor drift from the target area. Do not
contaminate water when disposing of equipment wash water or rinsate."
Precautionary Statements immediately
following the User Safety
Recommendations
53
-------
Description
Amended Labeling Language
Placement on Label
Entiy Prohibition Period for all
end-use products with uses within
the scope of the Worker Protection
Standard for Agricultural
Pesticides
"Entry (including early entry that would otherwise be permitted under the WPS) by any person - other
than a correctly trained and equipped handler who is performing a handling task permitted by the WPS -
is PROHIBITED for 48 hours following application. Do not allow entry by unprotected persons into the
treated area until 48-hour period is expired and the warning signs are removed."
Directions for Use under Agricultural
Use Requirements Box
Notification Requirements
"NOTIFICATION: Before the start of the application, notify workers of the application by warning them
orally and by posting warning signs at entrances to the treated area. The signs must bear the skull and
crossbones symbol and state: (1) "DANGER/PELIGRO," (2) "DO NOT ENTER/NO ENTRE," (3) the
date and time of treatment, (4) "Cycloate {or use other brand name} in use," and (5) name, address, and
telephone number of the applicator. Post the warning sign instead of the WPS sign for this application, but
follow all WPS requirements pertaining to location, legibility, size, and timing of posting and removal."
Directions for Use under Agricultural
Use Requirements Box
Special Early Entry Exception
"Special Early Entry Exception: Workers may enter the treated area during the first 48 hours following
application to plant crops, provided all of the following conditions are met:
(1) The special early entry workers must use motorized ground equipment that is equipped with an
enclosed cab that meets the definition in the Worker Protection Standard for Agricultural Pesticides [40
CFR 170.240(d)(5)] for dermal protection. In addition, these workers must:
- Wear the personal protective equipment required in the PPE section of this labeling for applicators,
- Either wear the type of respirator specified in the PPE section of this labeling or use an enclosed cab
with a properly functioning ventilation system that is used and maintained according to the
manufacturer's written operating instructions and that is declared in writing by the manufacturer or by a
government agency to provide at least as much respiratory protection as the type of respirator specified in
the PPE section of this labeling,
- Be provided and have immediately available for use in an emergency when they must exit the cab in the
treated area: chemical-resistant gloves, and, if using an enclosed cab that provides respiratory protection, a
respirator of the type specified in the PPE section of this labeling,
- Take off any PPE that was worn in the treated area before reentering the cab, and
- Store all such PPE in a chemical-resistant container, such as a plastic bag, to prevent contamination of
the inside of the cab.
(2) Employers of the special early entry workers must make sure that these workers:
- Have received training equivalent to WPS pesticide handler training before entering the treated area,
- Are provided with the specified type of respirator, and the respirator fits them correctly and is maintained
as required in the WPS for handlers, and
- Are provided all of the WPS protections for early entry workers, including PPE instructions, labeling
information and instructions, decontamination sites, and duties related to providing, cleaning, and
maintaining the PPE for early-entry workers."
Directions for Use under Agricultural
Use Requirements Box
54
-------
Description
Amended Labeling Language
Placement on Label
General Application Restrictions
"Do not apply this product in a way that will contact workers or other persons, either directly or through
drift. Only protected handlers may be in the area during application."
Place in the Direction for Use directly
above the Agricultural Use Box.
General Application Restrictions
"Chemigation is prohibited."
Place near the beginning of the
Direction for Use section.
Application Restrictions for garden
beets, spinach, and sugarbeets
''Garden Beets, Spinach, and Sugar Beets:"
"Maximum of 2/3 gallon (4 pounds active ingredient) per application and one application per crop cycle:
Directions for Use associated with
each crop listed
Application Restrictions for dry
bulk fertilizer
"Impregnation of dry bulk fertilizer is permitted in commercial settings only. On-farm impregnation of
dry bulk fertilizer is prohibited. All persons involved in the impregnation process are considered pesticide
handlers and must wear the handler personal protective equipment and follow the engineering control
requirements specified on this labeling, rf at any time during the impregnation process, including loading
of the impregnated fertilizer into the trucks for transporting, the system does not provide inhalation
protection equivalent to an organic-vapor removing respirator, all persons at the impregnation site must
wear the respirator required on this labeling for handlers."
Directions for Use associated with the
dry bulk fertilizer instructions
1 PPE that is established on the basis of Acute Toxicity of the end-use product must be compared to the active ingredient PPE in this document The more protective PPE must be placed in the product
labeling. For guidance on which PPE is considered more protective, see PR Notice 93-7.
2 Instruction to Registrant: Drop the "N" type prefilter from the respirator statement if the pesticide product contains, or is used with, oil.
55
-------
D. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this Reregistration Eligibility Decision (RED) for cycloate.
Persons other than the registrants may generally distribute or sell such products for 50 months from
the date of issuance of this RED. However, existing stocks time frames will be established case-by-
case, depending on the number of products involved, the number of label changes and other factors.
Refer to "Existing Stocks of Pesticide Products; Statement of Policy," as prescribed in the Federal
Register of June 26, 1991 (56 FR 29362) (FRL-3846-4).
The Agency has determined that registrants may distribute and sell cycloate products bearing
old labels/labeling for 26 months from the date of issuance of this RED. Persons other than the
registrants may generally distribute or sell such products for 50 months from the date of issuance of
this RED. Registrants and persons other than the registrants remain obligated to meet pre-existing
label requirements and existing stocks requirements applicable to products they sell or distribute.
56
-------
VL APPENDICES
57
-------
58
-------
Appendix A. CYCLOATE (Case No. 2125): Table of Use Patterns Eligible for Reregistration
Site
Application Type
Application Timing
Application Equipment
Formulation
[EPA Reg. No.]
Maximum Single
Application Rate
(Ibs. a.L/acre)
Maximum No.
of Applications
Per Season
Maximum
Seasonal Rate
(Ibs. a.i./acre)
Preharvest
Interval
(Days)
Use Directions and Limitations
Beets, Garden
Soil broadcast or band1
Pre-plant, or at-planting, or
immediately post-planting
Ground
6 IbsVgal. EC
[73637-5]
3.0-4.0
One
Not specified
(NS)6
Not
specified
/lsjc\7
(JNb)
Use on mineral soils only. Use lower rate on sandy soils
and higher rate on heavier soils. When the product is
applied in combination with fluid fertilizers, do not
apply over 150 Ibs. of actual nitrogen per acre.
Beets, Sugar
Soil broadcast or band1
Pre-plant, or at-planting, or
immediately post-planting
Ground
Soil broadcast or band1
Fall
Ground
Soil incorporated
Post-emergence
Irrigation
6 IbsVgal. EC
[73637-5]
61bs/gal EC
[73637-5]
61bs/gal EC
[ID010015]3
[OR010022]3
[WA010023]3
3 0-40
4.0
4.0
One2
One2
NS
NS6
NS6
NS6
NS7
NS7
NS7
Use on mineral soils only. Use lower rate on sandy soils
and higher rate on heavier soils. Injury may result in
highly saline or alkaline soils. May be tanked mixed
with the herbicide EPTC for pre-plant use on sugarbeets
grown in MI, MN, OH, and the Red River Valley area
ofND.
Recommended only in the states of ID, MN, MT, ND,
OR, and WY. Apply and incorporate in late fall before
ground freezes.
Incorporate to a maximum depth of 3 inches and
minimum depth of 2 inches.
Spinach
Soil broadcast or band1
Pre-plant, or at-planting, or
immediately post-planting
Ground
Soil broadcast
Pre-plant
Ground
6 IbsVgal. EC
[73637-5]
61bs/gal EC
[OR010023]3
[WA010021]3
[WA010022]3
304
405
3.24
One
NS
NS6
NS6
NS7
NS7
Use on mineral soils only.
Incorporate to a maximum depth of 3 inches and
minimum depth of 2 inches.
59
-------
Site
Application Type
Application Timing
Application Equipment
Spinach seed soil incorporated
Formulation
[EPA Reg. No.]
6 Ibs./gal. EC
[WA020003]
Maximum Single
Application Rate
(Ibs. a.L/acre)
3.0
Maximum No.
of Applications
Per Season
NS
Maximum
Seasonal Rate
(Ibs. a.i./acre)
NS6
Preharvest
Interval
(Days)
NS7
Use Directions and Limitations
EC = Emulsifiable Concentrate
1 For band treatment, reduce the amount of product proportional to the row spacing and band width to be treated.
2 If the product is applied to sugarbeets in the fall, it should not be re-applied the following spring.
3 Use directions were extracted from a LUIS Report dated 10/15/01.
4 Dose rate recommended in AR, CO, CT, DE, IL, MA, MD, ME, MS, NH, NJ, NY, NC, OH, OK, PA, SC, TX, VT, VA and western TN.
5 Dose rate recommended in CA only.
6 Maximum seasonal rate must be specified on the label.
7 PHI must be specified on the label.
60
-------
Appendix B. Data Supporting Guideline Requirements for the Reregistration of Cycloate
GUIDE TO APPENDIX B
Appendix B contains a listing of data requirements which support the reregistration for active ingredients
within the chemical case covered by this RED. It contains generic data requirements that apply in all products,
including data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following formats:
1. Data Requirement (Columns 1, 2 & 3). The data requirements are listed in the order of New Guideline
Number and appear in 40 CFR §158. The reference numbers accompanying each test refer to the test
protocols set in the Pesticide Assessment Guidance, which are available from the National Technical
Information Service, 5285 Port Royal Road, Springfield, VA 22161-0002, (703) 487-4650.
2. Use Pattern (Column 4). This column indicates the use patterns for which the data requirements apply.
The following letter designations are used for the given use patterns.
A. Terrestrial food
B. Terrestrial feed
C. Terrestrial nonfood
D. Aquatic food
E. Aquatic nonfood outdoor
F. Aquatic nonfood industrial
G. Aquatic nonfood residential
H. Greenhouse food
I. Greenhouse nonfood
J. Forestry
K. Residential
L. Indoor food
M. Indoor nonfood
N. Indoor medical
O. Indoor residential
3. Bibliographical Citation (Column 5). If the Agency has acceptable data in its files, this column lists the
identification number of each study. Normally, this is the Master Record Identification (MRID) Number,
but may be a "GS" number if no MRID number has been assigned. Refer to the Bibliography (Appendix
D) for a complete citation of the study.
61
-------
Appendix B. Data Supporting Guideline Requirements for the Reregistration of Cycloate
New
Guideline
Number
Old
Guideline
Number
Requirement
Use
Pattern
Bibliographical Citation(s)
PRODUCT USE CHEMISTRY
830.1600
830.1620
830.1670
830.1700
830.6302
830.6303
830.6304
830.7220
830.7300
830.7840
830.7860
830.7950
830.7370
830.7550
830.7000
830.7050
830.6313
61-2A
61-2B
62-1
63-2
63-3
63-4
63-6
63-7
63-8
63-9
63-10
63-11
63-12
None
63-13
Starting Materials and Manufacturing Process
Description of Production Process
Discussion of Formation of Impurities
Preliminary Analysis
Color
Physical State
Odor
Boiling Point/Boiling Range
Density, Relative Density, Bulk Density
Solubility on TGAI
Vapor Pressure
Dissociation Constant in Water
Octanol/Water Partition Coefficient
pH of Water Solutions or Suspensions
Ultraviolet/Visible Absorption
Stability on TGAI
All
A,B
All
All
All
All
All
All
All
41614702
41614701
41582401
41582401 (Upgradable), Data Gap
41582401
41920603
41582401
Data Gap
41582401 (Upgradable), Data Gap
ECOLOGICAL EFFECTS
850.2100
850.2200
850.2300
850.1075
850.1010
71-1A
71-2A/2B
71-4A
71-4B
72-1 A
72- 1C
72-2A
Avian Acute Oral Toxicity, Bobwhite Quail on
TGAI
Avian Subacute Dietary Toxicity, Bobwhite
Quail on TGAI
Avian Subacute Dietary Toxicity, Mallard
Duck on TGAI
Avian Subacute Dietary Toxicity, Bobwhite
Quail or Mallard Duck on Cycloate Sulfoxide
Avian Reproduction, Bobwhite Quail on TGAI
Avian Reproduction, Mallard Duck on TGAI
Fish Acute Toxicity, Bluegill Sunfish
Fish Acute Toxicity, Rainbow Trout
Invertebrate Acute Toxicity
A,B
A,B
A,B
A,B
A,B
00132798, Ace. 072166 & 073005
00145554, Ace. 072166
42090306, Ace. 072166
Reserved
Data Gap
Data Gap
00084743, 00143654, 41614703,
45608401, Ace. 072166 & 090620
00143655, 05001497
62
-------
New
Guideline
Number
850.1035
850.1300
850.1350
850.1730
850.4100
850.4150
850.4225
850.4250
850.4400
850.3020
Old
Guideline
Number
72-3A
72-3C
72-4A
72-4B
72-6B
122-1A
122-1B
123-1A
123-1B
123-2
141-1
Requirement
Estuarine/Marine Fish Acute Toxicity on
TGAI
Estuarine/Marine Invertebrate Acute Toxicity
on TGAI
Fish-Early Life Stage on TGAI
Aquatic Invertebrate Life Cycle on TGAI
Fish BCF (Aquatic Organism Accumulation)
Seedling Germination/Seedling Emergence,
Tier 1(10 most sensitive species from testing
with parent compound) on TEP
Vegetative Vigor, Tier 1(10 most sensitive
species from testing with parent compound) on
TEP
Seedling Germination/Seedling Emergence,
Tier 2(10 most sensitive species from testing
with parent compound) on TEP
Vegetative Vigor, Tier 2(10 most sensitive
species from testing with parent compound) on
TEP
Aquatic Plant Growth, Tier 2 (5 most sensitive
species from testing with parent compound) on
TEP
Honey Bee Acute Contact Toxicity on TGAI
Use
Pattern
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Bibliographical Citation(s)
Data Gap
Data Gap
Data Gap
05001497, Data Gap
Reserved
Data Gap
Data Gap
Reserved
43889101, Reserved
Data Gap
00036935
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.6100
870.6200A
870.3100
870.3150
870.3200
None
870.3465
81-1
81-2
81-3
81-4
81-5
81-6
81-7
81-8
82-1 A
82-1B
82-2
None
82-4
Acute Oral Toxicity, Rat
Acute Dermal Toxicity, Rabbit
Acute Inhalation Toxicity, Rat
Primary Eye Irritation, Rabbit
Primary Skin Irritation
Dermal Sensitization, Guinea Pig
Acute Delayed Neurotoxicity, Rat
Acute Neurotoxicity Screening Battery, Rat
90-Day Subchronic Feeding, Rodent
90-Day Subchronic Feeding, Nonrodent (Dog)
21 -Day Dermal, Rat
21 -Day Inhalation, Rat
90-Day Inhalation, Rat
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
00132271, 00132791, 13279091,
Ace. 073004
00132792, 41589203, 42237001,
42868601
00132791, 13279091
41708101,41729901
42854001, 42921701, 42985701
42921701,43968001
40458401
42090305, 43323801
43552101
40049601-2, 42237001, 42985701
63
-------
New
Guideline
Number
870.6200B
870.4100
870.4200
870.3700
870.3800
None
870.4300
870.6300
870.5140
870.5375
870.5500
870.7485
None
870.7600
Old
Guideline
Number
82-7
83-1A
83-1B
83-2A
83-2B
83-3A
83-3B
83-4
None
83-5
83-6
84-2A
84-2B
84-4
85-1
None
85-2
Requirement
Subchronic Neurotoxicity Study
Chronic Feeding Toxicity, Rodent
Chronic Feeding Toxicity, Nonrodent (Dog)
Chronic Carcinogenicity (Feeding), Rat
Chronic Carcinogenicity (Feeding), Mouse
Prenatal Developmental Toxicity, Rat
Prenatal Developmental Toxicity, Rabbit
2-Generation Reproduction, Rat
3-Generation Reproduction, Rat
Combined Chronic Toxicity/ Carcinogenicity
Study, Rat
Developmental Neurotoxicity Study, Rat
Gene Mutation (Ames Test)
Structural Chromosomal Aberration
Other Genotoxic Effects
General Metabolism, Rat/Mouse/Monkey
14-Day Oral Metabolism
Dermal Absorption (Penetration), Rat
Use
Pattern
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Bibliographical Citation(s)
42921701, 42985701, 43967801
00077787, 00137735, 92025028
40458401
00077787, 00077789, 00137735,
92025028
00031592,41920604
00146659
42694901
00132795, 41333402, 41589203,
41691901
00132795
00077787,00137735
Data Gap
40825201,41582401-2
41614704-5,41629901
40825201, 41614705, 41629901
00132796, 00138177, 42090303-5,
42169101, 43043401, 92025034
42090303-5
00164351, 40229701, 43712502
OCCUPATIONAL/RESIDENTIAL EXPOSURE
875.1100
875.1300
231
232
Estimation of Dermal Exposure at Outdoor
Sites
Estimation of Inhalation Exposure at Outdoor
Sites
A,B
A,B
43712501-3, 43739701, Reserved
43712501-3, 43739701, Reserved
ENVIRONMENTAL FATE
835.2120
835.2240
835.2410
835.2370
835.4100
835.4200
835.4400
161-1
161-2
161-3
161-4
162-1
162-2
162-3
Hydrolysis
Photodegradation, Water
Photodegradation, Soil on Cycloate Sulfoxide
Photodegradation, Air
Aerobic Soil Metabolism Study
Anaerobic Soil Metabolism Study
Anaerobic Aquatic Metabolism Study
A,B
A,B
A,B
A,B
A,B
A,B
A,B
00149662
42249701
Reserved
42541101 (Supplemental)
41582403,42812901
00162652 (Supplemental)
42997901
64
-------
New
Guideline
Number
835.1230
835.1240
835.4240
835.1410
835.6100
835.1850
835.1900
835.1950
None
None
None
None
Old
Guideline
Number
163-1
163-2
164-1
165-1
165-2
165-4
166-2
166-3
167-1
167-2
Requirement
Leaching and Adsorption/Desorption
Laboratory Volatilization from Soil
Terrestrial Field Dissipation Study #1
Terrestrial Field Dissipation Study #2
Confined Accumulation in Rotational Crops
Field Accumulation in Rotational Crops
Bioaccumulation in Fish, Bluegill Sunfish
Small Scale Retrospective Ground Water
Large Scale Retrospective Ground Water
Field Runoff
Surface Water Monitoring
Use
Pattern
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Bibliographical Citation(s)
41920603
41920602
41582404-5 (Upgradable)
Data Gap
42409001
Data Gap
41920601
Reserved
Reserved
Reserved
Reserved
RESIDUE CHEMISTRY
860.1300
860.1340
860.1380
860.1480
860.1500
860.1520
860.1360
171-4A
171-4B
171-4C
171-4D
171-4E
171-4J
171-4K
171-4L
171-4M
Nature of the Residue, Plants
Nature of the Residue, Livestock
Residue Analytical Method, Plants
Residue Analytical Method, Animals
Storage Stability
Magnitude of Residues in Meat, Milk, Poultry
and Eggs
Crop Field Trials, Garden Beet
Crop Field Trials, Spinach
Crop Field Trials, Sugarbeet
Crop Field Trials, Swiss Chard
Processed Food, Sugarbeet (refined sugar,
dried pulp and molasses)
Multiresidue Methods (3- and 4-
hydroxycycloate metabolites)
A,B
A,B
A,B
A,B
A,B
A,B
A,B
00093480, 42090301-2
43273101,43392701
00115084,00115097,43523801,
44489501
00145578, 43392701
41582402, 41582406, 43501601,
44051801,44551001
43392701
42919703, 42939701, 92025031
41640301,42919703
41640303, 42919702, 92025030
45679801
42939701-2
Data Gap
65
-------
66
-------
Appendix C. Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP Public Regulatory
Docket, located in Room 119, Crystal Mall #2, 1801 S. Bell Street, Arlington, VA 22202-4501. It is
open Monday through Friday, excluding legal holidays, from 8:30 AM to 4 PM.
The cycloate docket initially contained preliminary risk assessments and related documents as of
May 12, 2004. Sixty days later, the comment period closed. The Agency then considered comments
and added the formal "Response to Comments" documents to the docket. All documents, in hard
copy form, may be viewed in the OPP docket room or downloaded or viewed via the Agency's
website at http://www.epa.sov/pesticides/reregistration/status.htm. In addition, the technical support
documents for cycloate are available through EPA Dockets, under docket ID number OPP-2004-
0234. The public may access EPA Dockets at http://www.epa.gov/edockets. These documents include:
BEAD Documents:
1. Evaluation of Cycloate Chemigation (David Donaldson & William Phillips, September 8, 2004);
and
2. Preliminary Analysis of Cycloate Mitigation for Extension of the Re-Entry Interval in Spinach
and Dry Bulk Fertilizer Impregnation in Sugar Beets (David Donaldson, Nicole Zinn & William
Phillips, October 12, 2004).
HEP Documents:
1. HED Response to Helm Agro US, Inc. on Inhalation Occupational Exposure Assessment (John
Liccione, October 2, 2004).
EFED Documents:
1. Comparison of Cycloate Estimated Environmental Concentrations in Wildlife Food Items with
Expanded Suite of Mammalian Reproduction Endpoints (Michael Davy, September 21, 2004).
Other Documents:
1. Response #1 to EPA Final Cycloate Inquiries from American Sugarbeet Growers Association
(Luther Markwart, September 22, 2004);
2. Response #2 to EPA Final Cycloate Inquiries from American Sugarbeet Growers Association
(Luther Markwart, October 12, 2004);
3. Response #1 to EPA Final Cycloate Inquiries from Washington State University (Jane Thomas,
September 7, 2004); and
4. Response #2 to EPA Final Cycloate Inquiries from Washington State University (Jane Thomas,
September 24, 2004).
67
-------
68
-------
Appendix D. Citations Considered to Be Part of the Data Base Supporting the Reregistration
Eligibility Decision (Bibliography)
GUIDE TO APPENDIX D
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated elsewhere in the
Reregistration Eligibility Document. Primary sources for studies in this bibliography have been
the body of data submitted to EPA and its predecessor agencies in support of past regulatory
decisions. Selections from other sources including the published literature, in those instances
where they have been considered, are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study." In the case of
published materials, this corresponds closely to an article. In the case of unpublished materials
submitted to the Agency, the Agency has sought to identify documents at a level parallel to the
published article from within the typically larger volumes in which they were submitted. The
resulting "studies" generally have a distinct title (or at least a single subject), can stand alone for
purposes of review and can be described with a conventional bibliographic citation. The Agency
has also attempted to unite basic documents and commentaries upon them, treating them as a
single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically by
Master Record Identifier, or "MRID" number. This number is unique to the citation, and should
be used whenever a specific reference is required. It is not related to the six-digit "Accession
Number" which has been used to identify volumes of submitted studies (see paragraph 4(d)(4)
below for further explanation). In a few cases, entries added to the bibliography late in the review
may be preceded by a nine character temporary identifier. These entries are listed after all MRID
entries. This temporary identifying number is also to be used whenever specific reference is
needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry consists of a
citation containing standard elements followed, in the case of material submitted to EPA, by a
description of the earliest known submission. Bibliographic conventions used reflect the standard
of the American National Standards Institute (ANSI), expanded to provide for certain special
needs.
a Author. Whenever the author could confidently be identified, the Agency has chosen to show
a personal author. When no individual was identified, the Agency has shown an identifiable
laboratory or testing facility as the author. When no author or laboratory could be identified,
the Agency has shown the first submitter as the author.
69
-------
b. Document date. The date of the study is taken directly from the document. When the date is
followed by a question mark, the bibliographer has deduced the date from the evidence
contained in the document. When the date appears as (????), the Agency was unable to
determine or estimate the date of the document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to create or enhance
a document title. Any such editorial insertions are contained between square brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing parentheses
include (in addition to any self-explanatory text) the following elements describing the
earliest known submission:
(1) Submission date. The date of the earliest known submission appears immediately
following the word "received."
(2) Administrative number. The next element immediately following the word "under" is the
registration number, experimental use permit number, petition number or other
administrative number associated with the earliest known submission.
(3) Submitter. The third element is the submitter. When authorship is defaulted to the
submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the trailing parentheses
identifies the EPA accession number of the volume in which the original submission of
the study appears. The six-digit accession number follows the symbol "CDL," which
stands for "Company Data Library." This accession number is in turn followed by an
alphabetic suffix which shows the relative position of the study within the volume.
70
-------
BIBLIOGRAPHY
MRID CITATION
31592 Lowry, I; Arceo, R.I; Goldenthal, E.I. (1979) Lifetime Oral Study in Mice: IRDC
No. 153-012. (Unpublished study received Mar 26, 1980 under 476-1978; prepared
by International Research and Development Corp., submitted by Stauffer Chemical
Co., Richmond, Calif.; CDL:242069-A)
36935 Atkins, E.L.; Greywood, E.A.; Macdonald, R.L. (1975) Toxicity of Pesticides and
Other Agricultural Chemicals to Honey Bees: Laboratory Studies. By University of
California, Dept. of Entomology. ?: UC, Cooperative Extension. (Leaflet 2287;
published study)
77787 Trutter, I A.; Kundzins, W.; Ulland, B.M.; et al. (1979) 24-month Chronic Feeding
Study in Rats: Ro-Neet Technical: Project No. 132-134. Final rept. (Unpublished
study received Sep 4, 1979 under 476-1978; prepared by Hazleton Laboratories
America, Inc., submitted by Stauffer Chemical Co., Richmond, Calif; CDL:240914-
A; 237974)
77789 Stauffer Chemical Company (1969) Ro-Neet: Data Summary. (Unpublished study
received Nov 15, 1978 under 476-1978; CDL:237974-A)
84743 Bullock, C. (1968) Thiocarbamate Herbicides-Mosquito Fish Bio- assay:
lexicological Summary T-1272. (Unpublished study received Oct 8, 1981 under
476-2107; submitted by Stauffer Chemical Co., Richmond, Calif; CDL:246020-G)
93480 Gray, R.A.; Tomlinson, GA. (1967) Metabolism of Radioactive S-Ethyl
Cyclohexylethylthiocarbamate (Ro-Neet) in Sugar Beets. (Unpublished study
received Feb 14, 1967 under 7F0522; submitted by Stauffer Chemical Co.,
Richmond, Calif; CDL:090621-A)
115097 Stauffer Chemical Co. (1976) Ro-Neet 6-E: Residue Data. (Compilation;
unpublished study received Nov 23, 1976 under 476-1979; CDL:226968-A)
132271 Beliles, R. (1965) Diazinon Safety Evaluation on Fish and Wildlife: Bobwhite
Quail, Goldfish, Sunfish, and Rainbow Trout. Interim rept. (Unpublished study
received Sep 2, 1983 under 100-461; prepared by Woodard Research Corp.,
submitted by Ciba-Geigy Corp., Greensboro, NC; CDL:251138-K)
132791 Miller, I; Billow, T. (1981) Ro-Neet 7.2E (Lot # BGJ2451, G-48): (Acute Toxicity
on Rats & Rabbits): Laboratory Report T-6429. (Unpublished study received Nov
30, 1983 under 476-EX-106; submitted by Stauffer Chemical Co., Richmond, CA;
CDL:072165-C)
71
-------
BIBLIOGRAPHY
MRID CITATION
132792 Stuart, B.; MacAskill, S.; Chaffee, M.; et al. (1982) Acute Inhalation Study with Ro-
Neet 6-E in Rats: T-l 1065. (Unpublished study received Nov 30, 1983 under 476-
EX-106; submitted by Stauffer Chemical Co., Richmond, CA; CDL:072165-D)
132795 Goldenthal, E.; Jessup, D.; Geil, R; et al. (1979) Three Generation Reproduction
Study in Rats: (Ro-Neet Technical): 153-019; T- 6340. (Unpublished study received
Nov 30, 1983 under 476-EX-106; prepared by International Research and
Development Corp., submitted by Stauffer Chemical Co., Richmond, CA;
CDL:072165-G)
132796 Chin, T.; Clement, R; Freudenthal, R; et al. (1983) Comparative Pharmacokinetics/
Metabolism Study of Ro-Neet in Rats and Mice: T-l 0424. (Unpublished study
received Nov 30, 1983 under 476- EX-106; submitted by Stauffer Chemical Co.,
Richmond, CA; CDL: 072165-1)
132798 Fletcher, D. (1983) Report to: Acute Oral Toxicity Study with Ro-Neet Technical in
Bobwhite Quail: T-l 1188. (Unpublished study received Nov 30 1983 under 476-
EX-106; prepared by Bio- Life Assoc., Ltd., submitted by Stauffer Chemical Co.,
Richmond, CA; CDL:072166-A)
137735 Sprague, G.; Thomassen, R; Zwicker, G.; et al. (1984) Two-Year Oral Toxicity
Study with Ro-Neet Technical in Rats: T-10114. Final rept. (Unpublished study
received Mar 20, 1984 under 476-106; submitted by Stauffer Chemical Co.,
Richmond, CA; CDL: 252686-A; 252687; 252688; 252689)
138177 Chin, T.; Clement, R.; Killinger, I; et al. (1984) Pharmacokinetics/Metabolism
Study of Ro-Neet in Monkeys: T-l 1017. (Unpublished study received Mar 20, 1984
under 476-106; submitted by Stauffer Chemical Co., Richmond, CA; CDL:252700-
A)
143654 McAllister, W.; Cohle, P. (1984) Acute Toxicity of Ro-Neet Technical to Bluegill
Sunfish (Lepomis macrochirus): Static Acute Toxicity Report #31561. Unpublished
study prepared by Analytical Bio-Chemistry Laboratories, Inc. 52 p.
143655 Forbis, A; Burgess, D. (1984) Acute Toxicity of Ro-Neet Technical to Daphnia
magna: Static Acute Toxicity Report #31787. Unpublished study prepared by
Analytical Bio-Chemistry Laboratories, Inc. 33 p.
145554 Beavers, I (1984) A Dietary LC50 Study in the Bobwhite with Ro-Neet Technical:
Final Report: Project No. 144-121. Unpublished study prepared by Wildlife
International Ltd. 14 p.
72
-------
BIBLIOGRAPHY
MRID
CITATION
145578
146659
149662
164351
5001497
Stauffer Chemical Co. (1984) [Residue Study of Cycloate andN-
Ethylcyclohexylamine in Meat and Milk]. Unpublished compilation. 145 p.
Keets, S.; Leist, P.; Mercieca, M. (1985) A Teratology Study in Rats with Ro-Neet:
Final Report: Project No. WIL-27020. Unpublished study prepared by WIL
Research Laboratories, Inc. 267 p.
Myers, H.; Bartell, L. (1983) Hydrolysis Studies of Cycloate: Report No. WRC 83-
73. Unpublished report prepared by Stauffer Chemical Company. 17 p.
Jeffcoat, A. (1986) Dermal Absorption of Ro-Neet in Rats: Final Report: RTI/3586-
10/F; 001870. Unpublished study prepared by Research Triangle Institute. 197 p.
Sanders, H.O. (1970) Toxicities of some herbicides to six species of freshwater
crustaceans. Journal of the Water Pollution Control Federation 42(8): 1544-1550.
40049601
40049602
40229701
40458401
40825201
Knapp, H.; Thomassen, R (1986) Subchronic Inhalation Study with Ro-Neet
Technical in Rats: Final Report: Project No. T-12621. Unpublished study prepared
by Stauffer Chemical Co. in coopera- tion with Hazleton Laboratories America and
Duke University Medical Center. 378 p.
Knapp, H.; Thomassen, R. (1984) Subchronic Inhalation Study with Ro-Neet in
Rats: Project No. T-l 1705. Unpublished study prepared by Stauffer Chemical Co.
356 p.
Killinger, J. (1987) Addendum 1 to Study - Dermal Absorption of Ro-Neet in Rats:
Study No.: T-l2735. Unpublished study prepared by RTI Laboratories. 12 p.
Kurtz, P.; Knapp, H.; Thomassen, R (1987) One-year Chronic Oral Toxicity Study
with Ro-Neet in Beagle Dogs: T-l2635: Final Re- port. Unpublished study prepared
by Stauffer Chemical Co. 391 p.
Majeska, I (1988) Mutagenicity Evaluation in L5178Y Mouse Lymphoma Multiple
Endpoint Test Forward Mutation Assay: Ro-Neet Technical: T-12045: EHC/P/270.
Unpublished study prepared by ICI Americas, Inc. 34 p.
73
-------
BIBLIOGRAPHY
MRID
CITATION
41333402
Gilles, P.; Richter, A. (1989) A Two-Generation Reproduction Study in Female
Rats with R-4572: (Molinate): Final Report: Lab Report Nos. T-13218; OECD
416; USEPA 540/9-82-025. Unpublished study prepared by Ciba-Geigy
Environmental Health Center. 748 p.
41582401
41582402
41582403
41582404
41582405
41582406
Eya, B. (1990) Cycloate: Physical Properties: Lab Project Number: ENV-024: RR
90-097B. Unpublished study prepared by ICI Americas, Inc. 46 p.
Majeska, I (1985) Mutagenicity Evaluation in Salmonella typhimurium: Ro-Neet
Technical: Lab Project Number: T-12044. Unpublished study prepared by Stauffer
Chemical Co. 20 p.
Spillner, C. (1989) Identification of Cycloate Soil Metabolites: Aerobic Soil
Metabolism: Lab Project Number: PMS-306: RR 89-063B. Unpublished study
prepared by ICI Americas, Inc. 56 p.
Curry, K. (1989) Ro-Neet 6-E: Field Dissipation Study for Terrestrial Food Crop
Uses Cycloate, California, 1987-1988: Lab Project Number: RP 87-02: RR 89-
041B. Unpublished study prepared by ICI Americas, Inc. 185 p.
Curry, K; Riggle, B.; Hoag, R. (1989) Ro-Neet 6-E: Field Dissipation Study for
Terrestrial Food Crop Uses Cycloate California, 1988: Lab Project Number: RSO2-
88-120: RR 89-019B. Unpublished study prepared by ICI Americas, Inc. 181 p.
McKay, J. (1989) Cycloate: Storage Stability Study: Crops and Soil: Storage
Stability Validation for Cycloate in Raw Agricultural Commodities and Soil: Lab
Project Number: WRC 89-20. Unpublished study prepared by ICI Americas, Inc.
98 p.
41589203
Knapp, H. (1982) Evaluation of Male Fertility Following Four-Week Inhalation
Exposure to Ordram Technical in Rats: Lab Project No: T-10494. Unpublished
study prepared by Stauffer Chemical Co. 120 p.
41614701
Nelson, N. (1990) Analysis and Certification of Product Ingredients in Ro-Neet
Selective Herbicide: Lab Project Number: APP/008. Unpublished study prepared by
ICI Americas, Inc., Western Research Center. 120 p.
74
-------
BIBLIOGRAPHY
MRID
CITATION
41614702
41614703
41614704
41614705
41629901
41640301
41640303
41691901
41708101
41729901
Javdani, K. ; Nelson, N (1990) Description of Beginning Materials and
Manufacturing Process and Discussion of the Formation of Impurities for Ro-Neet:
Lab Project Number: RR90/399B. Unpublished study prepared by ICI Americas
Inc., Western Research Center. 46 p.
Tapp, J.; Sankey, S.; Gaunter, I ; Stanley, R et al. (1990) Cycloate: Determination
of Acute Toxicity to Rainbow Trout (Salmo gairdneri): Lab Project Number:
S057/F/FT42/90. Unpublished study prepared by ICI, Bnxham Laboratory. 19 p.
Mackay, J. (1990) Cycloate: An Evaluation in the In Vitro Cytogenetic Assay in
Human Lymphocytes: Lab Project Number: SV0383. Unpublished study prepared
by ICI Central Toxicology laboratory. 32 p.
Majeska, J. (1985) Mutagenicity Evaluation in Bone Marrow Micronucleus: Lab
Project Number: T/12054. Unpublished study published by Environmental Health
Center. 14 p.
Stauffer Chemical Co. (1985) Mutagenicity Evaluation in Mouse Lymphoma
Multiple Endpoint Test Cytogenetic Assay: Lab Project Number: T/12046.
Unpublished study prepared by Stauffer Chemical Co. 25 p.
Iwata, Y. (1987) Cycloate and Its Principal Degradate, N-ethylcy- clohexanamine -
Magnitude of Residues on Spinach: Crop Field Trials: Lab Project Number:
RRC87/51. Unpublished study prepared by Stauffer Chemical Company. 95 p.
Iwata, Y. (1987) Cycloate and Its Principal Degradate, N-ethylcy- clohexanamine -
Magnitude of Residues on Sugarbeets: Crop Field Trials: Lab Project Number:
RRC87/49. Unpublished study prepared by Stauffer Chemical Company. 120 p.
Minor, J.; Turnier, J. (1990) A Two-Generation Reproduction Study in Rats with R-
2063 (T-13268): Final Report: Lab Project Number: T 13268. Unpublished study
prepared by Ciba-Geigy Environmental Health Ctr. 262 p.
Rattray, N.; Lees, D. (1990) Cycloate: Skin Sensitization to the Guinea Pig: Lab
Project Number: CTL/P/2823: GG4774: GG4763. Unpublished study prepared by
ICI Central Toxicology Laboratory. 31 p.
Rattray, N., Lees, D. (1990) Cycloate: Skin Sensitization to the Guinea Pig: Lab
Project Number: CTL/P/2823: GG4774: GG4763. Unpublished study prepared by
ICI Central Toxicology Laboratory. 31 p.
75
-------
BIBLIOGRAPHY
MRID
CITATION
41920601
41920602
41920603
41920604
42090301
42090302
42090303
42090304
42090305
42090306
Subba-Rao, R; Tamichi, E. (1991) Cycloate: Bioaccumulation in Bluegill Sunfish:
Lab Project Number: RR 91-045B: PMS 354: 39037. Unpublished study prepared
by ICI America, Inc. 106 p.
McGahen, L. (1991) Volatility of 14C-Cycloate Applied to Soil: Lab Project
Number: PMS-343: RR-91-006B. Unpublished study prepared by ICI Amencas,
Inc. Western Research Center and Pesticide Metabolism Center. 43 p.
Laster, W. (1991) Cycloate: Adsorption/Desorption in Four Soils: Lab Project
Number: 39229: 91-035B: PMS 359. Unpublished study prepared by ABC
Laboratories, Inc. 56 p.
Stonard, M. (1991) Cycloate: 18-Month Carcinogenicity Study in Mice: Lab Project
Number: CIL/P/3125: PM0728. Unpublished study prepared by ICI Central
Toxicology Laboratory. 1801 p.
Miller, M.; Barnes, I (1991) Metabolism of (carbon-14)-Cycloate in Sugar Beets:
Lab Project Number PMS 338: RR 91-057B. Unpublished study prepared by ICI
Americas, Inc. 167 p.
Barnes, I (1991) Metabolism of (carbon 14)-Cycloate in Spinach: Lab Project
Number: PMS337: RR91-056B. Unpublished study prepared by ICI Amencas Inc.
in coop with PTRL West, Inc. 127 p.
Bratt, H.; Davies, D. (1991) Cycloate: Repeat Dose Study (10 mg/kg) in the Rat:
Addendum to MRID 132796: Lab Project Number: CTL/P/ 3395: URO342.
Unpublished study prepared by ICI Central Tox. Lab. 39 p.
Lappin, G.; Trivedi, S. (1991) Cycloate: Excretion and Tissue Distribution of a
Single Low Oral Dose (10 mg/kg) and a Single Oral High Dose (160 mg/kg) in the
Female Rat: Addendum to MRID 132796: Lab Project Number: CTL/P/3292:
URO343. Unpublished study prepared by ICI Central Tox Lab. 33 p.
Kinsey, D.; Leah, A. (1991) Cycloate: 21-Day Dermal Toxicity to the Rat: Lab
Project Number: CTL/P/3352: LRO551. Unpublished study prepared by ICI Central
Tox Lab. 296 p.
Beavers, J. (1985) Ro-Neet Technical: A Dietary LC50 Study with the Mallard:
Final Report: Lab Project Number: 144-129: SPONSOR. Unpublished study
prepared by Wildlife International Ltd. 19 p.
76
-------
BIBLIOGRAPHY
MRID
CITATION
42237001
42249701
42409001
42541101
42694901
42812901
42854001
42868601
42919701
42919702
Lewis, R; Parr-Dobrzanski, R (1992) Cycloate: 21-Day Sub-Acute Inhalation
Toxicity Study in the Rat: Lab Project Number: CTL/P/3646: MRO147.
Unpublished study prepared by ICI, Alderley Park. 418 p.
Hillebrecht, W. (1992) Addendum Number 1 to MRID 148882: Cycloate
Photodegradation in Water: Lab Project Number: WRH-1/92. Unpublished study
prepared by ICI Americas, Inc. 24 p.
Barnes, L; Staub, R (1992) Cycloate: Confined Rotational Crop Study: Lab Project
Number: PMS 329: RR 92-052B. Unpublished study prepared by ICI Americas, Inc.
210 p.
Kwok, E.; Atkinson, R; Arey, I (1992) Gas-phase atmospheric chemistry of
selected Thiocarbamates. Environ. Sci. Technol. 26(9):1798-1807.
Horner, J. (1992) Cycloate: Developmental Toxicity Study in the Rabbit: Lab
Project Number: CTL/P/3810: RB0589. Unpublished study prepared by ICI Central
Toxicology Laboratory. 3 89 p.
Spillner, C. (1993) Cycloate: Aerobic Soil Metabolism Study: Response to EPA
Review Comments: Addendum 1: Lab Project Number: WRH-61693: 61693.
Unpublished study prepared by Zeneca, Inc. 5 p.
Hillebrecht, W. (1993) Letter Sent to Office of Pesticide Programs dated July 20,
1993: Cycloate acute neurotoxicity screening study: (preliminary findings).
Prepared by Zeneca Ag Products. 2 p.
Coombs, D. (1993) Cycloate: 3-Week Inhalation Neurotoxicity Study in Rats: Lab
Project Number: CTL/C/2934: ISN 305/930620. Unpublished study prepared by
Huntingdon Research Centre Ltd. 187 p.
Grant, C.; Herman, R. (1993) Ro-Neet 6-E: Magnitude of the Residue Study for
Cycloate on Sugar Beets; Spring Application: Lab Project Number: CYCL-91-MR-
03: RR 93-038B. Unpublished study prepared by Western Research Center, Zeneca
Ag Products. 203 p.
Grant, C.; Herman, R. (1993) Ro-Neet 6-E: Magnitude of the Residue Study for
Cycloate on Spinach; Fall Planting: Lab Project Number: CYCL-91-MR-01: RR 93-
036B. Unpublished study prepared by Western Research Center, Zeneca Ag
Products. 141 p.
77
-------
BIBLIOGRAPHY
MRID
CITATION
42919703
42921701
42939701
42939702
42985701
42997901
43043401
43273101
43323801
Grant, C; Herman, R (1993) Ro-Neet 6-E: Magnitude of the Residue Study for
Cycloate on Table Beets: Lab Project Number: CYCL-91-MR-02: RR 93-037B.
Unpublished study prepared by Western Research Center, Zeneca Ag Products. 150
P-
Rattray, N. (1993) Cycloate: Acute Neurotoxicity Study in Rats: (Final Report): Lab
Project Number: CTL/P/3952: AR5468. Unpublished study prepared by Zeneca
Central Toxicology Lab. 354 p.
Grant, C.; Herman, R (1993) Ro-Neet: Magnitude of the Residue Study for
Cycloate on Table Beets: Lab Project Number: CYCL-92-MR-01: RR 93-063B.
Unpublished study prepared by Zeneca Ag Products, Western Research Center. 98 p.
Grant, C.; Herman, R (1993) Ro-Neet: Residue Processing Study for Cycloate on
Sugar Beets: Lab Project Number: CYCL-92-PR-01: RR 93-059B. Unpublished
study prepared by Zeneca Ag Products, Western Research Center; Wm. I Englar &
Associates, Inc. 92 p.
Horner, S. (1993) Cycloate: Subchronic Neurotoxicity Study in Rats: Lab Project
Number: CTL/P/4053: PR0938. Unpublished study prepared by Zeneca Central
Toxicology Lab. 3 86 p.
Eya, B.; Carley, S. (1993) Cycloate: Anaerobic Aquatic Soil Metabolism: Lab
Project Number: RR 93-079B. Unpublished study prepared by Zeneca Inc.,
Western Research Center. 85 p.
Marsh, I; Woollen, B.; Wilks, M. (1993) The Pharmacokinetics of Cycloate in
Man: Lab Project Number: CTL/P/3985: XH2276. Unpublished study prepared by
ZENECA Central Toxicology Lab. 40 p.
Lay, M. (1994) The Nature of the Residues of Orally Administered ((carbon 14)-
UL-cyclohexyl-ring) Cycloate in Tissues and Eggs of Laying Hens: Lab Project
Number: PMS 372: RR 93-066B: WIN 1403. Unpublished study prepared by
ZENECA Inc., Western Research Center. 224 p.
Lees, D. (1994) Cycloate: 21-Day Dermal Toxicity to the Rat: First Supplement:
Lab Project Number: CTL/P/3352: LR0551. Unpublished study prepared by Zeneca
Central Toxicology Lab. 70 p.
78
-------
BIBLIOGRAPHY
MRID
CITATION
43392701
43501601
43523801
43552101
43712501
43712502
43712503
43739701
Barnes, L; Miller, M; Staub, R. (1994) The Nature of the Residues of Orally
Administered ((carbon 14)-UL-cyclohexyl -ring)-Cycloate in Tissues and Milk of
Lactating Goats: Lab Project Number: PMS 373: RR 94-065B: WIND 15.
Unpublished study prepared by Zeneca Western Research Center. 217 p.
Herman, R. (1994) Cycloate: Storage Stability of Cycloate Metabolites in Raw
Beets and Spinach and Processed Sugar Beets (16-Month Interval-Interim Report):
Lab Project Number: CYCL/ 94/SS/01: RR/94/076B/INT. Unpublished study
prepared by Zeneca Ag Products. 3 5 p.
Herman, R. (1995) Ro-Neet: Determination of Cycloate, 3-Hydrocycloate, and 4-
Hydrocycloate in Crops by Gas Chromatography: Lab Project Number:
CYCL/92/AM/01: RR/94/044B. Unpublished study prepared by Zeneca Western
Research Center. 69 p.
Parr-Dobrzanski, R. (1994) Cycloate: 21-Day Sub-Acute Inhalation Toxicity Study
in the Rat: Lab Project Numbers: CTL/P/4432: MR0163. Unpublished study
prepared by Zeneca Central Toxicology Laboratory. 688 p.
Findlay, M.; Chester, G. (1995) Thiocarbamate Herbicide: Risk Assessment for
Mixer-Loader-Applicators Using Vehicle-Mounted Groundboom Spray Equipment:
Lab Project Number: WRH/BIOMON-1. Unpublished study prepared by Zeneca Ag
Products. 15 p.
Lythgoe, R; Platt, I (1995) Thiocarbamates: Comparative in vivo Percutaneous
Absorption Study in the Rat: Lab Project Number: CTL/P/4594: UR0445.
Unpublished study prepared by Zeneca Western Research Center. 46 p.
Storoni, H (1995) Cycloate: Volatility of Cycloate in Ro-Neet 6-E from Various
Dosimetry Patches: Lab Project Number: CYCL-94-OT-01: RR 94-035B.
Unpublished study prepared by Zeneca Western Research Center. 43 p.
Meier, D. (1995) Cycloate: Worker Exposure During Mixing, Loading, and
Application of Ro-Neet to Sugar Beets Using Ground Boom Equipment: Lab
Project Number: RR 95-013B: CYCL-94-AE-01: RR 94-042B. Unpublished study
prepared by Zeneca Ag Products. 162 p.
43889101
Christensen, G.; Canez, V.; Feutz, E. (1995) Tier 2 Non-Target Vegetative Vigor
Phytotoxicity Study Using AC 252,925 in a 2AS Formulation: Lab Project Number:
42125: 954-94-168: ECO 94-170. Unpublished study prepared by ABC Labs, Inc.
166 p.
79
-------
BIBLIOGRAPHY
MRID
CITATION
43967801
Homer, S. (1995) Cycloate: Subchronic Neurotoxicity Study in Rats: First Revision:
Addendum to MRID 42985701: Lab Project Number: CIL/P/4053: PR0938.
Unpublished study prepared by Zeneca Central Toxicology Lab. 840 p.
43968001
Rattray, N. (1995) Cycloate: Acute Neurotoxicity Study in Rats: First Revision:
Addendum to MRID 42921701: Lab Project Number: CTL/P/3952: AR5468.
Unpublished study prepared by Zeneca Central Toxicology Lab. 702 p.
44051801
Herman, R (1996) Cycloate: Storage Stability of Cycloate Metabolites in Raw
Table Beets and Spinach and Processed Sugar Beets: (25-Month Interval-Final
Report): Lab Project Number: CYCL-94-SS-01: RR 94-076B FIN. Unpublished
study prepared by Zeneca Ag Products. 58 p.
44489501
Wood, B. (1997) Cycloate: Independent Laboratory Validation of an Analytical
Method for the Determination of Cycloate, 3-Hydroxycycloate, and 4-
Hydroxycycloate in Crops by Gas Chromatography: Lab Project Number: 110.003:
RR 97-052B. Unpublished study prepared by North Coast Laboratories, Ltd. 77 p.
{OPPTS 860.1340}
44551001
Herman, R; Wiebe, L. (1998) Cycloate: Cold Storage Stability of (carbon 14)-
Cycloate in Sugar Beet Molasses (Reformat of TMR0745B for EPA Submission):
Lab Project Number: RR98-013B: CYCL-91-SS-01: WIND 6184. Unpublished
study prepared by Zeneca Ag Products. 36 p. {OPPTS 860.1380}
45608401
US. EPA (1977) Acute Toxicity of Ro-Neet 6E to Rainbow Trout. Unpublished
study prepared by Animal Biology Laboratory. 3 p.
45679801
Salzman, F. (2002) Cycloate: Magnitude of the Residue on Swiss Chard: Lab
Project Number: 03542: 03542.99-CAR15: 03542.99-CA65. Unpublished study
prepared by University of California, USDA and Rutgers Ag Research and
Education Center. 252 p.
92025028
Trutter, I; Kundzins, W.; Ulland, B.; et al. (1990) ICI Americas Inc. Phase 3
Reformat of MRID 00077787. 24-Month Chronic Feeding Study in Rats with
Cycloate Ro-Neet Technical: Report No. T-6119; Project No. 132-134. Prepared by
Hazleton Laboratories America Inc. 301 p.
80
-------
BIBLIOGRAPHY
MRID CITATION
92025030 Adelson, B.; McKay, I (1990) ICI Americas Inc. Phase 3 Reformat of MRID
00085727 and Related MRIDs 00093483, 00115097, 00140929, 00067275,
00115088, 00115094. Ro Neet 6-E Magnitude of the Residue on Sugar Beets: Lab
Study ID No. RR 89-082B. Prepared by ICI Americas, Inc., Western Research
Center. 391 p.
92025031 Adelson, B.; McKay, J. (1990) ICI Americas Inc. Phase 3 Reformat of MRID
00115082 and Related MRIDs 00115094, 00067275. Ro Neet 6-E Magnitude of
the Residue on Table Beets: Lab Study ID No. RR 90-002B. Prepared by ICI
Americas, Inc., Western Research Center. 94 p.
92025034 Chin, T.; Clement, R (1990) ICI Americas Inc. Phase 3 Reformat of MRID
00132796. Cycloate: Metabolism Study in the Rat: EHC Report No. and Study No
T-10424. Prepared by Environmental Health Centre. 95 p.
ACC 072166 /MRID 132798
Fletcher, D. (1983) Report to: Acute Oral Toxicity Study with Ro-Neet Technical in
Bobwhite Quail: T-l 1188. (Unpublished study received Nov 30 1983 under 476-
EX-106; prepared by Bio- Life Assoc., Ltd., submitted by Stauffer Chemical Co.,
Richmond, CA; CDL:072166-A)
ACC 073005 /MRID 143652
Stauffer Chemical Co. (19??) Fish and Wildlife Data: [Summary of Toxicity to Ro-
Neet]. Unpublished study. 1 p.
ACC 073044 /MRID 143648
Stauffer Chemical Co. (19??) Ro-Neet: Summary of Toxicology Data. Unpublished
study. 1 p.
ACC 090620 /MRID 20540
Johnston, C.D. (1963) Acute Eye Irritation Test of Six Experimental Compounds: R-
1910, R-2063-B, R-4572, N-2404, N-2790 andN-3684. (Unpublished study
received Nov 29,1965 under 7F0522; prepared by Woodard Research Corp.,
submitted by Stauffer Chemical Co., Richmond, CA; CDL:097555-C)
81
-------
82
-------
Appendix E. EPA's Batching of Cycloate Products for Meeting Acute Toxicity Data
Requirements for Reregistration
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing cycloate, the primary active
ingredient, the Agency has batched products which can be considered similar for purposes of acute
toxicity. Factors considered in the sorting process include each product's active and inert ingredients
(identity, percent composition and biological activity), type of formulation (e.g., emulsifiable
concentrate, aerosol, wettable powder, granular, etc.) and labeling (e.g., signal word, use
classification, precautionary labeling, etc.). Note: The Agency is not describing batched products as
"substantially similar," since some products within a batch may not be considered chemically similar
or have identical use patterns.
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Notwithstanding the batching process, the Agency reserves the right to require,
at any time, acute toxicity data for an individual product should that need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite a
single battery of six acute toxicological studies to represent all the products within that batch. It is the
registrants' option to participate in the process with all other registrants, only some of the other
registrants, only their own products within in a batch or to generate all the required acute
toxicological studies for each of their own products. If the registrant chooses to generate the data for
a batch, he/she must use one of the products within the batch as the test material. If the registrant
chooses to rely upon previously submitted acute toxicity data, he/she may do so provided that the data
base is complete and valid by today's standards (see acceptance criteria attached), the formulation
tested is considered by EPA to be similar for acute toxicity and the formulation has not been
significantly altered since submission and acceptance of the acute toxicity data. Regardless of
whether new data is generated or existing data is referenced, the registrants must clearly identify the
test material by EPA Registration Number. If more than one confidential statement of formula (CSF)
exists for a product, the registrant must indicate the formulation actually tested by identifying the
corresponding CSF.
In deciding how to meet the product-specific data requirements, registrants must follow the
directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI
Notice contains two response forms which are to be completed and submitted to the Agency within
90 days of receipt. The first form, "Data Call-in Response," asks whether the registrant will meet the
data requirements for each product. The second form, "Requirements Status and Registrant's
Response," lists the product-specific data required for each product, including the standard six acute
toxicity tests. A registrant who wishes to participate in a batch must decide whether he/she will
provide the data or depend on someone else to do so. If the registrant supplies the data to support a
batch of products, he/she must select the one of the following options: Developing Data (Option 1),
Submitting an Existing Study (Option 4), Upgrading an Existing Study (Option 5) or Citing an
Existing Study (Option 6). If a registrant depends on another's data, he/she must choose among: Cost
Sharing (Option 2), Offers to Cost Share (Option 3) or Citing an Existing Study (Option 6). If a
registrant does not want to participate in a batch, the choices are Options 1, 4, 5 or 6. However, a
registrant should know that choosing not to participate in a batch does not preclude other registrants
in the batch from citing his/her studies and offering to cost share (Option 3) those studies.
Two products were found which contain cycloate as the active ingredient. These products have
been placed into one batch in accordance with the active and inert ingredients and type of
formulation. Products with state registration are not included in the list.
83
-------
Batch 1
EPA Reg. No.
62719-403
71085-21
Percent Cycloate
73.9
73.9
Formulation Type
Liquid
Liquid
84
-------
Appendix F. List of Available Related Documents and Electronically Available Forms
Pesticide Registration Forms are available via the Agency's website at
http://www.epa.sov/opprd001/forms/. These forms are in PDF format and require the Acrobat reader.
Instructions
1. Print out and complete the forms. (Note: Form numbers that are bolded can be filled out on
your computer then printed).
2. The completed form(s) should be submitted in hard copy in accord with the existing policy.
3. Mail the forms, along with any additional documents necessary to comply with EPA
regulations covering your request, to the address below for the Document Processing Desk.
DO NOT fax or e-mail any form containing 'Confidential Business Information' or 'Sensitive
Information.'
If you have any problems accessing these forms, please contact Nicole Williams at (703)
308-5551 or by e-mail at Williams.nicole(a)jepa.sov.
The following Agency Pesticide Registration Forms are currently available via the Internet at
the following locations:
8570-1
8570-4
8570-5
8570-17
8570-25
8570-27
8570-28
8570-30
8570-32
8570-34
8570-35
8570-36
Application for Pesticide Registration/Amendment
Confidential Statement of Formula
Notice of Supplemental Registration of Distribution of a
Registered Pesticide Product
Application for an Experimental Use Permit
Application for/Notification of State Registration of a
Pesticide To Meet a Special Local Need
Formulator's Exemption Statement
Certification of Compliance with Data Gap Procedures
Pesticide Registration Maintenance Fee Filing
Certification of Attempt to Enter into an Agreement
with other Registrants for Development of Data
Certification with Respect to Citations of Data (PR
Notice 98-5)
Data Matrix (PR Notice 98-5)
Summary of the Physical/Chemical Properties (PR
Notice 98-1)
http://www. epa.sov/opprdOOl /forms/8 5 70-1 . pdf
http://www. epa.sov/opprdOOl/form s/8 5 70-4. pdf
http://www.epa.sov/opprd001/forms/8570-5.pdf
http://www.epa.sov/opprd001/forms/8570-17.pdf
http://www.epa.sov/opprd001/forms/8570-25.pdf
http://www.epa.sov/opprd001/forms/8570-27.pdf
http://www.epa.sov/opprd001/forms/8570-28.pdf
http://www.epa.sov/opprd001/forms/8570-30.pdf
http://www. epa.sov/opprdOOl /forms/8 5 70-32. pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-5.pdf
http://www. epa.sov/opppmsdl/PR Notices/pr98-5. pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-l.pdf
85
-------
8570-37
Self-Certification Statement for the Physical/Chemical
Properties (PR Notice 98-1)
http://www.epa.sov/opPpmsdl/PR Notices/pr98-l.pdf
Pesticide Registration Kit http://www.epa. sov/pesticides/registrationkit/
Dear Registrant:
For your convenience, we have assembled an online registration kit which contains the
following pertinent forms and information needed to register a pesticide product with the U.S.
Environmental Protection Agency's Office of Pesticide Programs (OPP):
1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug
and Cosmetic Act (FFDCA) as Amended by the Food Quality Protection Act (FQPA) of 1996.
2. Pesticide Registration (PR) Notices
a.
b.
c.
d.
e.
f
83-3 Label Improvement Program-Storage and Disposal Statements
84-1 Clarification of Label Improvement Program
86-5 Standard Format for Data Submitted under FIFRA
87-1 Label Improvement Program for Pesticides Applied through Irrigation Systems
(Chemigation)
87-6 Inert Ingredients in Pesticide Products Policy Statement
90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
95-2 Notifications, Non-notifications, and Minor Formulation Amendments
h. 98-1 Self Certification of Product Chemistry Data with Attachments (This document is in
PDF format and requires the Acrobat reader.)
Other PR Notices can be found at http://www.epa. gov/opppmsdl/PR Notices
3. Pesticide Product Registration Application Forms (These forms are in PDF format and will
require the Acrobat reader).
a. EPA Form No. 8570-1, Application for Pesticide Registration/Amendment
b. EPA Form No. 8570-4, Confidential Statement of Formula
c. EPA Form No. 8570-27, Formulatpr's Exemption Statement
d. EPA Form No. 8570-34, Certification with Respect to Citations of Data
EPA Form No. 8570-35, Data Matrix
e.
4.
General Pesticide Information (Some of these forms are in PDF format and will require the
Acrobat reader).
a. Registration Division Personnel Contact List
b. Biopesticides and Pollution Prevention Division (BPPD) Contacts
c. Antimicrobials Division Organizational Structure/Contact List
d. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements (PDF
format)
e. 40 CFR § 156, Labeling Requirements for Pesticides and Devices (PDF format)
f. 40 CFR § 15 8. Data Requirements for Registration (PDF format)
g. 50 F.R. 48833, Disclosure of Reviews ofPesticide Data (November 27, 1985)
Before submitting your application for registration, you may wish to consult some additional
sources of information. These include:
1.
The Office ofPesticide Programs' website.
86
-------
2. The booklet "General Information on Applying for Registration of Pesticides in the United
States," PB92-221811, available through the National Technical Information Service (NTIS) at
the following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
Springfield, VA 22161-0002
Telephone: (703) 605-6000
3. The National Pesticide Information Retrieval System (NPIRS) of Purdue University's Center
for Environmental and Regulatory Information Systems. This service does charge a fee for
subscriptions and custom searches. You can contact NPIRS by telephone at (765) 494-6614 or
through their website.
4. The National Pesticide Information Center (NPIC) can provide information on active
ingredients, uses, toxicology and chemistry of pesticides. You can contact NPIC by telephone
at (800) 858-7378 or through their website at http://www.ncis.orst.edu.
The Agency will return a notice of receipt of an application for registration or amended
registration, experimental use permit, or amendment to a petition if the applicant or petitioner
encloses with his submission a stamped, self-addressed postcard. The postcard must contain the
following entries to be completed by OPP:
• Date of receipt;
• EPA identifying number; and
Product Manager assignment.
Other identifying information may be included by the applicant to link the acknowledgment of
receipt to the specific application submitted. EPA will stamp the date of receipt and provide the EPA
identifying file symbol or petition number for the new submission. The identifying number should be
used whenever you contact the Agency concerning an application for registration, experimental use
permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are properly coded
and assigned to your company, please include a list of all synonyms, common and trade names,
company experimental codes, and other names which identify the chemical (including "blind" codes
used when a sample was submitted for testing by commercial or academic facilities). Please provide
a chemical abstract system (CAS) number if one has been assigned.
87
-------
88
-------
Appendix G. Generic Data Call-In
See the following table for a list of generic data requirements. Note that a complete Data
Call-In (DCI), with all pertinent instructions, is being sent to registrants under separate cover.
89
-------
90
-------
Appendix H. Product Specific Data Call-In
See attached table for a list of product-specific data requirements. Note that a complete
Data Call-In (DCI), with all pertinent instructions, is being sent to registrants under separate cover.
91
-------
92
-------
Appendix I. List of Registrants Sent this Data Call-In
93
-------
94
------- |